Non-Hodgkin lymphoma

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

aggressive B-cell lymphomas

diffuse large B-cell lymphoma; stages I-II (nonbulky [<7.5 cm] and low risk [smIPI 0-1) excluding stage II with extensive mesenteric disease: initial presentation

1st line – R-CHOP-21 ± radiation therapy

Back

1st line –

R-CHOP-21 ± radiation therapy

Initial treatment for stage I-II diffuse large B-cell lymphoma (excluding stage II with extensive mesenteric disease) that is nonbulky (<7.5 cm) and low risk (stage-modified International Prognostic Index [smIPI] 0-1) is 3 cycles of R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given on day 1 of a 21-day cycle), followed by interim restaging with positron emission tomography/computed tomography (PET/CT) scan.[48]

Depending on response, further cycles of R-CHOP-21 (to a total of 4-6 cycles) with or without involved-site radiation therapy (ISRT), or ISRT alone, or a repeat biopsy (to guide further treatment) is indicated.[48]

For young women in whom radiation to the breast carries potential risk of breast cancer, R-CHOP-21 alone may be preferred.[100]

R-CHOP-21 is relatively well tolerated, with the main toxicities being hematologic (from bone marrow suppression), infection (from neutropenia), cardiac (from doxorubicin), alopecia, infusion-related respiratory symptoms (with or without bronchospasm), chills, fever, and hypotension from rituximab.[156]

Alternative first-line regimens are recommended for certain patients (e.g., those with poor left ventricular function; those who are very frail; those ages >80 years with comorbidities).[48][51]

See local specialist protocol for dosing guidelines.

Primary options

R-CHOP-21

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Older patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

Consider – CNS prophylaxis

Back

Consider –

CNS prophylaxis

Treatment recommended for SOME patients in selected patient group

Central nervous system (CNS) relapse occurs in approximately 5% of patients with diffuse large B-cell lymphoma (DLBCL) following initial treatment, and is associated with a poor prognosis.[103]

The use of CNS prophylaxis is controversial and it is not routinely recommended. CNS prophylaxis can be considered for patients with high-risk disease, including those with a high-risk score on the CNS-International Prognostic Index (i.e., CNS-IPI 4-6); kidney or adrenal gland involvement; testicular lymphoma; primary cutaneous DLBCL, leg type; or stage IE DLBCL of the breast.[48][87][104][105] See Criteria.

The optimal approach to CNS prophylaxis is unclear. Typically, high-dose systemic methotrexate and/or intrathecal methotrexate and/or intrathecal cytarabine are given during or after treatment.[48][105]

In DLBCL patients receiving CNS prophylaxis, CNS relapse rates are similar regardless of route of administration (intrathecal vs. intravenous) and timing (during vs. after treatment).[106][107]

Leucovorin prophylaxis can minimize toxicity associated with methotrexate (e.g., myelosuppression, gastrointestinal toxicity, hepatotoxicity). All patients receiving high-dose methotrexate should receive leucovorin rescue therapy.[48]

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

diffuse large B-cell lymphoma; stages I-II (bulky [≥7.5 cm] and low risk [smIPI 0-1]) excluding stage II with extensive mesenteric disease: initial presentation

1st line – R-CHOP-21 ± radiation therapy

Back

1st line –

R-CHOP-21 ± radiation therapy

Initial treatment for stage I-II diffuse large B-cell lymphoma (excluding stage II with extensive mesenteric disease) that is bulky (≥7.5 cm) and low risk (stage-modified International Prognostic Index [smIPI] 0-1) is 3-4 cycles of R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone given on day 1 of a 21-day cycle), followed by interim restaging with PET/CT scan.[48]

Depending on response, further cycles of R-CHOP-21 (to a total of 6 cycles) with or without involved-site radiation therapy (ISRT), or repeat biopsy (to guide further treatment) is indicated.[48]

R-CHOP is relatively well tolerated, with the main toxicities being hematologic (from bone marrow suppression), infection (from neutropenia), cardiac (from doxorubicin), alopecia, infusion-related respiratory symptoms (with or without bronchospasm), chills, fever, and hypotension from rituximab.[156]

Alternative first-line regimens are recommended for certain patients (e.g., those with poor left ventricular function; those who are very frail; those ages >80 years with comorbidities).[48][51]

See local specialist protocol for dosing guidelines.

Primary options

R-CHOP-21

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Older patients receiving R-CHOP chemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

Consider – CNS prophylaxis

Back

Consider –

CNS prophylaxis

Treatment recommended for SOME patients in selected patient group

Central nervous system (CNS) relapse occurs in approximately 5% of patients with diffuse large B-cell lymphoma (DLBCL) following initial treatment, and is associated with a poor prognosis.[103]

In DLBCL patients receiving CNS prophylaxis, CNS relapse rates are similar regardless of route of administration (intrathecal vs. intravenous) and timing (during vs. after treatment).[106][107]

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

diffuse large B-cell lymphoma; stages I-II (nonbulky or bulky, and high risk [smIPI >1]) excluding stage II with extensive mesenteric disease: initial presentation

1st line – R-CHOP-21 or Pola-R-CHP

Back

1st line –

R-CHOP-21 or Pola-R-CHP

Initial treatment for stage I-II diffuse large B-cell lymphoma (excluding stage II with extensive mesenteric disease) that is nonbulky or bulky, and high risk (stage-modified International Prognostic Index [smIPI] >1) is R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone given on day 1 of a 21-day cycle) or Pola-R-CHP (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone) for 2-4 cycles, followed by interim restaging with PET/CT or CT scan.[48] Depending on response, further cycles of the initial regimen (to a total of 6 cycles), or repeat biopsy (to guide further treatment) is indicated.[48]

Alternative first-line regimens are recommended for certain patients (e.g., those with poor left ventricular function; those who are very frail; those ages >80 years with comorbidities).[48][51]

See local specialist protocol for dosing guidelines.

Primary options

R-CHOP-21

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

Pola-R-CHP

polatuzumab vedotin

and

rituximab

and

cyclophosphamide

and

doxorubicin

and

prednisone

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Older patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

Consider – CNS prophylaxis

Back

Consider –

CNS prophylaxis

Treatment recommended for SOME patients in selected patient group

Central nervous system (CNS) relapse occurs in approximately 5% of patients with diffuse large B-cell lymphoma (DLBCL) following initial treatment, and is associated with a poor prognosis.[103]

In DLBCL patients receiving CNS prophylaxis, CNS relapse rates are similar regardless of route of administration (intrathecal vs. intravenous) and timing (during vs. after treatment).[106][107]

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

diffuse large B-cell lymphoma; stage II with extensive mesenteric disease; stages III-IV: initial presentation

1st line – R-CHOP-21 or Pola-R-CHP or R-EPOCH

Back

1st line –

R-CHOP-21 or Pola-R-CHP or R-EPOCH

Initial treatment for diffuse large B-cell lymphoma that is stage II with extensive mesenteric disease, or stages III-IV, is R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone given on day 1 of a 21-day cycle) or Pola-R-CHP (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone; for patients with International Prognostic Index [IPI] ≥2) for 2-4 cycles, followed by interim restaging with PET/CT or CT scan.[48] Depending on response, further cycles of the initial regimen (to a total of 6 cycles), or repeat biopsy (to guide further treatment) is indicated.[48]

Other recommended treatment regimens include rituximab plus dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH). Dose-adjusted R-EPOCH should be considered for patients with a poor prognosis (e.g., those with MYC translocations and BCL2 and/or BCL6 rearrangements [i.e., “double-hit” or “triple-hit”]) or those with HIV infection.[48][101][102]

Alternative first-line regimens are recommended for certain patients (e.g., those with poor left ventricular function; those who are very frail; those ages >80 years with comorbidities).[48][51]

See local specialist protocol for dosing guidelines.

Primary options

R-CHOP-21

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

Pola-R-CHP

polatuzumab vedotin

and

rituximab

and

cyclophosphamide

and

doxorubicin

and

prednisone

Secondary options

R-EPOCH

rituximab

and

etoposide

and

prednisone

and

vincristine

and

cyclophosphamide

and

doxorubicin

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Older patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

Consider – CNS prophylaxis

Back

Consider –

CNS prophylaxis

Treatment recommended for SOME patients in selected patient group

Central nervous system (CNS) relapse occurs in approximately 5% of patients with diffuse large B-cell lymphoma (DLBCL) following initial treatment, and is associated with a poor prognosis.[103]

In DLBCL patients receiving CNS prophylaxis, CNS relapse rates are similar regardless of route of administration (intrathecal vs. intravenous) and timing (during vs. after treatment).[106][107]

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

diffuse large B-cell lymphoma; primary refractory disease or early relapse (<12 months)

1st line – chimeric antigen receptor (CAR) T-cell therapy or salvage chemotherapy

Back

1st line –

chimeric antigen receptor (CAR) T-cell therapy or salvage chemotherapy

Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have refractory disease or relapse, most of whom will ultimately die from their lymphoma.[108][109] Relapse should be confirmed by biopsy before proceeding with treatment.

CAR T-cell therapy is recommended for patients who have primary refractory disease or early relapse.[48] Options include axicabtagene ciloleucel or lisocabtagene maraleucel.

Patients should receive bridging therapy (e.g., with chemotherapy) as clinically indicated, while waiting for administration of CAR T-cell therapy.[48]

Patients should be carefully assessed for suitability for CAR T-cell therapy. Toxicities include cytokine release syndrome, neurotoxicity, and prolonged cytopenias, which may limit feasibility of use to younger or fit older patients. In the US, CAR T-cell therapy is only available through a Risk Evaluation and Mitigation Strategies (REMS) program.

Patients unsuitable for CAR T-cell therapy can be considered for a clinical trial or salvage chemotherapy.[48] Salvage chemotherapy regimens include: dexamethasone and cytarabine (DHA) and a platinum agent (cisplatin, carboplatin, or oxaliplatin) ± rituximab; gemcitabine plus dexamethasone and a platinum agent (cisplatin or carboplatin) ± rituximab; ifosfamide, carboplatin, and etoposide (ICE) ± rituximab.[48]

See local specialist protocol for dosing guidelines.

Primary options

axicabtagene ciloleucel

lisocabtagene maraleucel

Secondary options

DHA + platinum agent

dexamethasone

-- AND --

cytarabine

-- AND --

cisplatin

carboplatin

oxaliplatin

DHA + platinum agent + rituximab

dexamethasone

-- AND --

cytarabine

-- AND --

cisplatin

carboplatin

oxaliplatin

-- AND --

rituximab

gemcitabine

-- AND --

dexamethasone

-- AND --

cisplatin

carboplatin

gemcitabine

-- AND --

dexamethasone

-- AND --

cisplatin

carboplatin

-- AND --

rituximab

ICE

ifosfamide

and

carboplatin

and

etoposide

ICE + rituximab

ifosfamide

and

carboplatin

and

etoposide

and

rituximab

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

Patients on high-dose ifosfamide should receive mesna to prevent hemorrhagic cystitis.

All patients on salvage regimens should receive a granulocyte colony-stimulating factor (G-CSF) concomitantly with chemotherapy.[1][155]

2nd line – chimeric antigen receptor (CAR) T-cell therapy or bispecific antibody therapy or loncastuximab tesirine or selinexor

Back

2nd line –

chimeric antigen receptor (CAR) T-cell therapy or bispecific antibody therapy or loncastuximab tesirine or selinexor

For adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy, the CAR T-cell therapy options include axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel if not used previously.[48]

Other options after two or more lines of systemic therapy are: bispecific antibody therapy (epcoritamab, glofitamab); loncastuximab tesirine; selinexor (including patients with disease progression after transplant or CAR T-cell therapy).[48][114][115][116][117]

See local specialist protocol for dosing guidelines.

Primary options

epcoritamab

glofitamab

loncastuximab tesirine

selinexor

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

diffuse large B-cell lymphoma; late relapse (>12 months): intention to proceed to autologous stem cell transplant

1st line – salvage chemotherapy

Back

1st line –

salvage chemotherapy

Salvage chemotherapy regimens are recommended for patients with late relapse who are eligible for intensive consolidation and intended for autologous stem cell transplant (ASCT).[48]

Salvage chemotherapy regimens include: dexamethasone and cytarabine (DHA) and a platinum agent (cisplatin, carboplatin, or oxaliplatin) ± rituximab; gemcitabine plus dexamethasone and a platinum agent (cisplatin or carboplatin) ± rituximab; ifosfamide, carboplatin, and etoposide (ICE) ± rituximab.[48]

See local specialist protocol for dosing guidelines.

Primary options

DHA + platinum agent

dexamethasone

-- AND --

cytarabine

-- AND --

cisplatin

carboplatin

oxaliplatin

DHA + platinum agent + rituximab

dexamethasone

-- AND --

cytarabine

-- AND --

cisplatin

carboplatin

oxaliplatin

-- AND --

rituximab

gemcitabine

-- AND --

dexamethasone

-- AND --

cisplatin

carboplatin

gemcitabine

-- AND --

dexamethasone

-- AND --

cisplatin

carboplatin

-- AND --

rituximab

ICE

ifosfamide

and

carboplatin

and

etoposide

ICE + rituximab

ifosfamide

and

carboplatin

and

etoposide

and

rituximab

Consider – autologous stem cell transplant ± radiation therapy, or chimeric antigen receptor (CAR) T-cell therapy

Back

Consider –

autologous stem cell transplant ± radiation therapy, or chimeric antigen receptor (CAR) T-cell therapy

Treatment recommended for SOME patients in selected patient group

If a complete or partial response is achieved following salvage chemotherapy, then consolidation therapy with ASCT (with or without involved-site radiation therapy [ISRT]) is recommended, if suitable (e.g., based on age, general fitness, comorbidities).[48]

CAR T-cell therapy (axicabtagene ciloleucel; tisagenlecleucel; lisocabtagene maraleucel) is an option if a partial response is achieved following salvage chemotherapy.[48]

See local specialist protocol for dosing guidelines.

Primary options

axicabtagene ciloleucel

tisagenlecleucel

lisocabtagene maraleucel

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

Patients on high-dose ifosfamide should receive mesna to prevent hemorrhagic cystitis.

All patients on salvage regimens should receive a granulocyte colony-stimulating factor (G-CSF) concomitantly with chemotherapy.[1][155]

2nd line – chimeric antigen receptor (CAR) T-cell therapy or bispecific antibody therapy or loncastuximab tesirine or selinexor

Back

2nd line –

chimeric antigen receptor (CAR) T-cell therapy or bispecific antibody therapy or loncastuximab tesirine or selinexor

See local specialist protocol for dosing guidelines.

Primary options

epcoritamab

glofitamab

loncastuximab tesirine

selinexor

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

diffuse large B-cell lymphoma; late relapse (>12 months): no intention to proceed to autologous stem cell transplant

1st line – chimeric antigen receptor (CAR) T-cell therapy or monoclonal antibody therapy or salvage chemotherapy

Back

1st line –

chimeric antigen receptor (CAR) T-cell therapy or monoclonal antibody therapy or salvage chemotherapy

CAR T-cell therapy, monoclonal antibody therapy, or second-line chemotherapy regimens can be considered for patients with late relapse who are not intended for autologous stem cell transplant (ASCT).

Options include: lisocabtagene maraleucel; polatuzumab vedotin ± bendamustine ± rituximab; tafasitamab plus lenalidomide; second-line chemotherapy (e.g., CEOP [cyclophosphamide, etoposide, vincristine, prednisone] ± rituximab; dose-adjusted EPOCH [etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin] ± rituximab; GemOx [gemcitabine plus oxaliplatin] ± rituximab; gemcitabine plus dexamethasone and a platinum agent [cisplatin or carboplatin] ± rituximab) if not used first-line.[48][110][111][112][113]

See local specialist protocol for dosing guidelines.

Primary options

lisocabtagene maraleucel

polatuzumab vedotin

and

bendamustine

polatuzumab vedotin

and

bendamustine

and

rituximab

tafasitamab

and

lenalidomide

CEOP

cyclophosphamide

and

etoposide

and

vincristine

and

prednisone

CEOP + rituximab

cyclophosphamide

and

etoposide

and

vincristine

and

prednisone

and

rituximab

EPOCH

etoposide

and

prednisone

and

vincristine

and

cyclophosphamide

and

doxorubicin

EPOCH + rituximab

etoposide

and

prednisone

and

vincristine

and

cyclophosphamide

and

doxorubicin

and

rituximab

GemOx

gemcitabine

and

oxaliplatin

GemOx + rituximab

gemcitabine

and

oxaliplatin

and

rituximab

gemcitabine

-- AND --

dexamethasone

-- AND --

cisplatin

carboplatin

gemcitabine

-- AND --

dexamethasone

-- AND --

cisplatin

carboplatin

-- AND --

rituximab

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

All patients on salvage regimens should receive a granulocyte colony-stimulating factor (G-CSF) concomitantly with chemotherapy.[1][155]

2nd line – chimeric antigen receptor (CAR) T-cell therapy or bispecific antibody therapy or loncastuximab tesirine or selinexor

Back

2nd line –

chimeric antigen receptor (CAR) T-cell therapy or bispecific antibody therapy or loncastuximab tesirine or selinexor

See local specialist protocol for dosing guidelines.

Primary options

epcoritamab

glofitamab

loncastuximab tesirine

selinexor

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

primary mediastinal large B-cell lymphoma: initial presentation

1st line – chemotherapy ± radiation therapy

Back

1st line –

chemotherapy ± radiation therapy

First-line treatment options for primary mediastinal large B-cell lymphoma (PMBCL) include: R-EPOCH (rituximab plus dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) for 6 cycles; R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone given on day 1 of a 21-day cycle) for 6 cycles ± involved-site radiation therapy (ISRT) to the mediastinum; or R-CHOP-14 (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone given on day 1 of a 14-day cycle) for 4-6 cycles.[48]

R-EPOCH is the preferred regimen in fit patients (who can tolerate more intensive chemotherapy), and in younger patients (as it avoids the need for radiation therapy which is associated with long-term complications).[118]

Patients treated with 4 cycles of R-CHOP-14 who achieve a complete response receive consolidation therapy with ICE (ifosfamide, carboplatin, and etoposide) with or without rituximab.[48][119]

See local specialist protocol for dosing guidelines.

Primary options

R-EPOCH

rituximab

and

etoposide

and

prednisone

and

vincristine

and

cyclophosphamide

and

doxorubicin

R-CHOP-21

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

Secondary options

ICE

ifosfamide

and

carboplatin

and

etoposide

ICE + rituximab

ifosfamide

and

carboplatin

and

etoposide

and

rituximab

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide or ifosfamide should receive mesna to prevent hemorrhagic cystitis.

Mesna is not required for less intensive cyclophosphamide-containing regimens (e.g., R-CHOP-21 [rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone given on day 1 of a 21-day cycle]).

Older patients receiving R-CHOP should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

primary mediastinal large B-cell lymphoma; partial response to initial treatment, or progressive/relapsed/refractory disease

1st line – pembrolizumab, or nivolumab ± brentuximab vedotin

Back

1st line –

pembrolizumab, or nivolumab ± brentuximab vedotin

Patients achieving only a partial response with initial treatment, or who have progressive, relapsed, or refractory disease (confirmed by biopsy) can be considered for second-line treatment, which includes: pembrolizumab, or nivolumab with or without brentuximab vedotin.[48]

Treatment options for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) can also be considered in these patients.

See local specialist protocol for dosing guidelines.

Primary options

pembrolizumab

nivolumab

and

brentuximab vedotin

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

primary CNS lymphoma

1st line – methotrexate-based chemotherapy ± consolidation therapy

Back

1st line –

methotrexate-based chemotherapy ± consolidation therapy

Optimal treatment for primary CNS lymphoma (PCNSL) involves two phases: induction and consolidation.

All patients who are clinically fit should be treated with high-dose methotrexate-based induction therapy.[53]

Induction therapy regimens include: high-dose methotrexate plus rituximab (with or without temozolomide); high-dose methotrexate plus vincristine, procarbazine, and rituximab (R-MPV); and high-dose methotrexate plus cytarabine, thiotepa, and rituximab.[53][120]

Whole-brain radiation therapy (WBRT) may be used as part of induction therapy (depending on the regimen and methotrexate dose), or used for palliative treatment of older and clinically unfit patients who are not candidates for systemic therapy.[53] While PCNSL is sensitive to WBRT, response is usually short-lived and neurotoxicity may occur (particularly in older patients).[120]

Patients achieving a complete response to induction therapy can be considered for consolidation therapy. Options include: high-dose chemotherapy (e.g., thiotepa plus cytarabine and carmustine; or thiotepa plus busulfan and cyclophosphamide) with autologous stem cell rescue; or high-dose cytarabine with or without etoposide.[120][53][121][122][123]

Low-dose WBRT may also be considered for consolidation if standard consolidation therapy is not an option.[124]

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and

rituximab

methotrexate

and

rituximab

and

temozolomide

R-MPV

methotrexate

and

vincristine

and

procarbazine

and

rituximab

methotrexate

and

cytarabine

and

thiotepa

and

rituximab

Secondary options

thiotepa

and

cytarabine

and

carmustine

thiotepa

and

busulfan

and

cyclophosphamide

cytarabine

and

etoposide

Plus – supportive care

Back

Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Consider – antiretroviral therapy (ART)

Back

Consider –

antiretroviral therapy (ART)

Treatment recommended for SOME patients in selected patient group

Primary CNS lymphoma may be associated with HIV/AIDS.[14][45]

If the patient is HIV positive, ART should be administered concurrently with systemic therapy.[53]

ART consists of multiple drugs from several classes and varies significantly depending on each individual patient with HIV. Request infectious disease consult to determine appropriate regimen for each patient.

For detailed information on ART, see HIV infection.

primary effusion lymphoma/body cavity lymphoma

1st line – EPOCH or CHOP

Back

1st line –

EPOCH or CHOP

Treatment includes EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).[48]

CHOP is relatively well tolerated, with the main toxicities being hematologic (from bone marrow suppression), infection (from neutropenia), cardiac (from doxorubicin), and alopecia.[156]

Rituximab is not indicated because most cases of PEL are CD20-negative.

See local specialist protocol for dosing guidelines.

Primary options

EPOCH

etoposide

and

prednisone

and

vincristine

and

cyclophosphamide

and

doxorubicin

CHOP

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

Consider – antiretroviral therapy (ART)

Back

Consider –

antiretroviral therapy (ART)

Treatment recommended for SOME patients in selected patient group

Primary effusion lymphoma (PEL) occurs most commonly in immunocompromised patients (e.g., those with HIV infection).

ART is important along with chemotherapy in treating HIV-positive PEL patients.[163]

For detailed information on ART, see HIV infection.

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Mesna is not required for less intensive cyclophosphamide-containing regimens (e.g., CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone]).

Burkitt lymphoma: initial presentation

1st line – R-CODOX-M or R-CODOX-M/R-IVAC or R-EPOCH or R-hyper-CVAD

Back

1st line –

R-CODOX-M or R-CODOX-M/R-IVAC or R-EPOCH or R-hyper-CVAD

Burkitt lymphoma is a highly aggressive NHL that requires treatment with intensive multiagent chemotherapy regimens.

Treatment is based on age and risk-stratification (i.e., low risk or high risk).[48] Patients with normal serum lactate dehydrogenase (LDH), or stage I disease and completely resected abdominal lesion, or single extra-abdominal mass <10 cm, are considered low risk.[48] All other patients are considered high risk.

Initial treatment for patients age <60 years with low-risk disease includes: R-CODOX-M (rituximab plus cyclophosphamide, doxorubicin, vincristine, and methotrexate); R-EPOCH (rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin); R-hyper-CVAD (rituximab plus cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with methotrexate and cytarabine).[48]

Initial treatment for patients ages <60 years with high-risk disease includes: R-CODOX-M alternating with R-IVAC (rituximab plus ifosfamide, etoposide, and cytarabine); R-hyper-CVAD; R-EPOCH (for those not able to tolerate aggressive regimens).[48]

Initial treatment for patients ages ≥60 years with low-risk or high-risk disease is R-EPOCH.[48]

A clinical trial (if available) or palliative ISRT is recommended for patients who do not achieve a complete response after initial treatment.[48]

See local specialist protocol for dosing guidelines.

Primary options

R-CODOX-M

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

methotrexate

R-IVAC

rituximab

and

ifosfamide

and

etoposide

and

cytarabine

R-EPOCH

rituximab

and

etoposide

and

prednisone

and

vincristine

and

cyclophosphamide

and

doxorubicin

R-hyper-CVAD

rituximab

and

cyclophosphamide

and

vincristine

and

doxorubicin

and

dexamethasone

and

methotrexate

and

cytarabine

Plus – CNS prophylaxis

Back

Plus –

CNS prophylaxis

Treatment recommended for ALL patients in selected patient group

Burkitt lymphoma has a propensity to spread to the central nervous system (CNS).

CNS prophylaxis (with high-dose systemic methotrexate and intrathecal methotrexate and/or cytarabine) is typically included in chemotherapy regimens for Burkitt lymphoma.

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

Plus – supportive care

Back

Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

Tumor lysis syndrome (TLS) is an oncologic emergency, particularly among patients with Burkitt lymphoma. Vigorous hydration (with intravenous fluids), phosphate-binding agents, and hypouricemic agents (e.g., allopurinol or rasburicase) should be used to prevent or treat TLS. TLS is characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and/or elevated serum lactate dehydrogenase (LDH), which can occur following treatment for NHL (or spontaneously in rare cases). See Complications.

Patients on high-dose cyclophosphamide or ifosfamide should receive mesna to prevent hemorrhagic cystitis.

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L].

Burkitt lymphoma: relapsed disease

1st line – salvage chemotherapy ± consolidation therapy

Back

1st line –

salvage chemotherapy ± consolidation therapy

Optimal treatment for relapsed Burkitt lymphoma is unclear.

If relapse occurs >6-18 months after initial treatment, the following regimens can be considered for second-line treatment (if not previously used): R-EPOCH (rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin); R-ICE (rituximab plus ifosfamide, carboplatin, and etoposide); R-IVAC (rituximab plus ifosfamide, etoposide, and cytarabine).[48]

Consolidation therapy with autologous stem cell transplant (with or without involved-site radiation therapy [ISRT]) should be considered after second-line treatment, depending on response.[48] Allogeneic stem cell transplantation (with or without ISRT) may be considered for consolidation therapy in select patients (if a donor is available).

Patients with relapse occurring <6 months after initial therapy, or who do not respond to second-line treatment, should be considered for a clinical trial or supportive/palliative care.[48]

See local specialist protocol for dosing guidelines.

Primary options

R-EPOCH

rituximab

and

etoposide

and

prednisone

and

vincristine

and

cyclophosphamide

and

doxorubicin

R-ICE

rituximab

and

ifosfamide

and

carboplatin

and

etoposide

R-IVAC

rituximab

and

ifosfamide

and

etoposide

and

cytarabine

Plus – supportive care

Back

Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

mantle cell lymphoma without TP53 mutation; localized disease: initial presentation

1st line – induction therapy (less aggressive) ± radiation therapy, or radiation therapy alone

Back

1st line –

induction therapy (less aggressive) ± radiation therapy, or radiation therapy alone

Treatment for mantle cell lymphoma (MCL) should be individualized based on disease stage, disease characteristics (e.g., TP53 mutation status), symptoms, and patient factors (e.g., age, performance status, comorbidities, desire/eligibility for aggressive therapy).

A small proportion of patients with MCL (10% to 15%) have indolent disease and can be observed if asymptomatic, but most have rapidly progressing advanced disease and need treatment at the time of diagnosis.[48][108]

Patients should be enrolled in a clinical trial if possible.

Initial treatment is typically given in phases (induction, consolidation, maintenance).

Less aggressive induction therapy (with or without involved-site radiation therapy [ISRT]) is recommended for patients with localized (stage I or stage II [nonbulky] disease.[48] Options include: bendamustine plus rituximab; VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone); R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone); lenalidomide plus rituximab; acalabrutinib plus rituximab.[48]

ISRT alone is also an option for patients with stage I or contiguous stage II (nonbulky) disease.[48]

Select patients (e.g., those with good performance status) with asymptomatic noncontiguous stage II (nonbulky) disease can be observed.[48]

See local specialist protocol for dosing guidelines.

Primary options

bendamustine

and

rituximab

VR-CAP

bortezomib

and

rituximab

and

cyclophosphamide

and

doxorubicin

and

prednisone

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

lenalidomide

and

rituximab

acalabrutinib

and

rituximab

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Older patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

mantle cell lymphoma without TP53 mutation; advanced disease: initial presentation, suitable for aggressive induction therapy and transplant

1st line – induction therapy (aggressive)

Back

1st line –

induction therapy (aggressive)

Patients should be enrolled in a clinical trial if possible.

Initial treatment is typically given in phases (induction, consolidation, maintenance).

Aggressive induction therapy is recommended for patients with advanced disease. Options include the following regimens.[48]

LyMA regimen: R-DHA (rituximab, dexamethasone, and cytarabine) plus a platinum agent (carboplatin, cisplatin, or oxaliplatin) followed by R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).[48]

NORDIC regimen: dose-intensified induction immunochemotherapy with rituximab plus cyclophosphamide, vincristine, doxorubicin, prednisone (known as maxi-CHOP) alternating with rituximab plus high-dose cytarabine.[48]

Rituximab plus bendamustine followed by rituximab plus high-dose cytarabine.[48]

TRIANGLE regimen, comprising R-CHOP plus a covalent Bruton tyrosine kinase (BTK) inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) alternating with R-DHA plus a platinum agent (carboplatin, cisplatin, or oxaliplatin).[48]

R-hyper-CVAD (rituximab plus cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with methotrexate and cytarabine).[48]

RBAC500 regimen (rituximab, bendamustine, plus cytarabine).[48]

Cardiac arrhythmias may occur with BTK inhibitors, particularly in patients with cardiac risk factors (e.g., hypertension and diabetes mellitus).[157][158][159][160][161] Clinical evaluation of cardiac history and function should be performed prior to initiating BTK inhibitors. Patients should be carefully monitored during treatment for cardiac arrhythmias and signs of deterioration of cardiac function, and clinically managed as appropriate. The risks and benefits of initiating or continued treatment with BTK inhibitors should be carefully assessed; alternative treatment may need to be considered.

In 2023, the manufacturer of ibrutinib voluntarily withdrew the US indication for MCL after a confirmatory phase 3 trial in patients with untreated MCL failed to demonstrate significant improvement in overall survival and complete response rate compared with placebo (despite meeting its primary endpoint of progression-free survival).[162] The US NCCN guidelines include ibrutinib as an option for patients with MCL (e.g., as part of the TRIANGLE regimen).[48] In Europe, ibrutinib continues to be approved for use in patients with relapsed or refractory MCL.

See local specialist protocol for dosing guidelines.

Primary options

R-DHA + platinum agent

rituximab

and

dexamethasone

and

cytarabine

-- AND --

carboplatin

cisplatin

oxaliplatin

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

NORDIC

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

and

cytarabine

rituximab

and

bendamustine

and

cytarabine

TRIANGLE regimen

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

and

dexamethasone

and

cytarabine

-- AND --

ibrutinib

acalabrutinib

zanubrutinib

-- AND --

carboplatin

cisplatin

oxaliplatin

R-hyper-CVAD

rituximab

and

cyclophosphamide

and

vincristine

and

doxorubicin

and

dexamethasone

and

methotrexate

and

cytarabine

Consider – maintenance and/or consolidation therapy

Back

Consider –

maintenance and/or consolidation therapy

Treatment recommended for SOME patients in selected patient group

Maintenance therapy with a covalent Bruton tyrosine kinase (BTK) inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) plus rituximab is recommended if patients achieve a complete response after aggressive induction therapy.[48]

Consolidation therapy with autologous stem cell transplant (followed by maintenance therapy with a covalent BTK inhibitor plus rituximab) is also an option if patients achieve a complete response after aggressive induction therapy.[48] Clinical trials are under way to address which patients with MCL are most likely to benefit from ASCT.

See local specialist protocol for dosing guidelines.

Primary options

ibrutinib

acalabrutinib

zanubrutinib

-- AND --

rituximab

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Older patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

mantle cell lymphoma without TP53 mutation; advanced disease: initial presentation, not suitable for aggressive induction therapy and transplant

1st line – induction therapy (less aggressive)

Back

1st line –

induction therapy (less aggressive)

Patients should be enrolled in a clinical trial if possible.

Initial treatment is typically given in phases (induction, consolidation, maintenance).

Less aggressive induction therapy is recommended for patients with advanced disease who are not suitable for aggressive induction therapy.[48] Options include: bendamustine plus rituximab; VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone); R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone); lenalidomide plus rituximab; acalabrutinib plus rituximab.[48]

See local specialist protocol for dosing guidelines.

Primary options

bendamustine

and

rituximab

VR-CAP

bortezomib

and

rituximab

and

cyclophosphamide

and

doxorubicin

and

prednisone

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

lenalidomide

and

rituximab

acalabrutinib

and

rituximab

Consider – maintenance therapy

Back

Consider –

maintenance therapy

Treatment recommended for SOME patients in selected patient group

Maintenance therapy with rituximab is recommended for patients who are in remission, and who are not candidates for ASCT, following less aggressive induction.[48]

See local specialist protocol for dosing guidelines.

Primary options

rituximab

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Older patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

mantle cell lymphoma with TP53 mutation: initial presentation

1st line – induction therapy

Back

1st line –

induction therapy

Patients with TP53-mutated mantle cell lymphoma (MCL) treated with conventional therapy (including transplant) have a poor prognosis.

Consolidative autologous stem cell transplant (ASCT) is not recommended for these patients.

Enrollment in a clinical trial is strongly recommended.[48]

The following options can be considered: zanubrutinib plus obinutuzumab plus venetoclax; TRIANGLE regimen, comprising R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) plus a covalent Bruton tyrosine kinase (BTK) inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) alternating with R-DHA [rituximab, dexamethasone, and cytarabine] plus a platinum agent (carboplatin, cisplatin, or oxaliplatin), if suitable for aggressive induction therapy; or aggressive induction therapy (including bendamustine plus rituximab; VR-CAP [bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone]; R-CHOP; lenalidomide plus rituximab; or acalabrutinib plus rituximab) if not suitable for aggressive induction therapy.[48]

See local specialist protocol for dosing guidelines.

Primary options

zanubrutinib

and

obinutuzumab

and

venetoclax

TRIANGLE regimen

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

and

dexamethasone

and

cytarabine

-- AND --

ibrutinib

acalabrutinib

zanubrutinib

-- AND --

carboplatin

cisplatin

oxaliplatin

bendamustine

and

rituximab

VR-CAP

bortezomib

and

rituximab

and

cyclophosphamide

and

doxorubicin

and

prednisone

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

lenalidomide

and

rituximab

acalabrutinib

and

rituximab

Consider – maintenance therapy

Back

Consider –

maintenance therapy

Treatment recommended for SOME patients in selected patient group

Maintenance therapy with a covalent Bruton tyrosine kinase (BTK) inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) plus rituximab is recommended after aggressive induction therapy with the TRIANGLE regimen.[48]

See local specialist protocol for dosing guidelines.

Primary options

ibrutinib

acalabrutinib

zanubrutinib

-- AND --

rituximab

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Older patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

mantle cell lymphoma: relapsed or refractory disease

1st line – Bruton tyrosine kinase (BTK) inhibitor, or lenalidomide + rituximab, or chimeric antigen receptor (CAR) T-cell therapy

Back

1st line –

Bruton tyrosine kinase (BTK) inhibitor, or lenalidomide + rituximab, or chimeric antigen receptor (CAR) T-cell therapy

Although mantle cell lymphoma (MCL) is initially responsive to chemotherapy, the disease inevitably relapses.[125][126]Lenz G, Dreyling M, Hoster E, et al. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol. 2005 Mar 20;23(9):1984-92.[127][128]

Preferred second-line treatments include: covalent BTK inhibitors (acalabrutinib; zanubrutinib), and lenalidomide plus rituximab.[48][129][130][131]

In 2023, the manufacturer of ibrutinib (a covalent BTK inhibitor) voluntarily withdrew the US indication for MCL after a confirmatory phase 3 trial in patients with untreated MCL failed to demonstrate significant improvement in overall survival and complete response rate compared with placebo (despite meeting its primary endpoint of progression-free survival).[162] In Europe, ibrutinib continues to be approved for use in patients with relapsed or refractory MCL.

For patients with relapsed or refractory disease after two or more lines of systemic therapy (including a covalent BTK inhibitor), options include: CAR T-cell therapy (brexucabtagene autoleucel, lisocabtagene maraleucel), or pirtobrutinib (a noncovalent [reversible] BTK inhibitor).[48][132][133]

See local specialist protocol for dosing guidelines.

Primary options

acalabrutinib

zanubrutinib

lenalidomide

and

rituximab

Secondary options

brexucabtagene autoleucel

lisocabtagene maraleucel

pirtobrutinib

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

high-grade B-cell lymphoma, not otherwise specified (NOS); double-hit lymphoma or triple hit lymphoma

1st line – R-EPOCH or R-CHOP-21

Back

1st line –

R-EPOCH or R-CHOP-21

High-grade B-cell lymphoma NOS appear blastoid or are intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, but lack an MYC and BCL2 and/or BCL6 rearrangement.

High-grade B-cell lymphomas with rearrangements of MYC and BCL2 or BCL6 are known as "double-hit" lymphomas; if all three are rearranged, they are referred to as "triple-hit" lymphomas.

The optimal treatment approach for patients with high-grade B-cell lymphoma (NOS, double-hit, or triple-hit) has not been established. Enrollment in a clinical trial is recommended.[48]

A rituximab-based chemotherapy regimen (e.g., R-dose-adjusted EPOCH [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab]) is recommended.[48][134] R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given on day 1 of a 21-day cycle) is an option for low-risk patients and those who are older or less fit.

See local specialist protocol for dosing guidelines.

Primary options

R-EPOCH

rituximab

and

etoposide

and

prednisone

and

vincristine

and

cyclophosphamide

and

doxorubicin

R-CHOP-21

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

Consider – CNS prophylaxis

Back

Consider –

CNS prophylaxis

Treatment recommended for SOME patients in selected patient group

Patients with high-grade B-cell lymphoma (NOS, double-hit, or triple-hit) are at high risk for central nervous system (CNS) involvement.

CNS prophylaxis can be considered in select patients with careful balancing of risk versus benefit. However, there are no robust data to support routine CNS prophylaxis, even among high-risk patients, and it is unclear if any prophylactic therapies effectively reduce the risk of CNS relapse. The optimal approach to CNS prophylaxis is unclear.

CNS prophylaxis may include high-dose systemic methotrexate and/or intrathecal methotrexate and/or intrathecal cytarabine, given during or after treatment.

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

aggressive T-cell lymphomas

enteropathy-associated T-cell lymphoma [EATL]/intestinal T-cell lymphoma; peripheral T-cell lymphoma, not otherwise specified (PTCL NOS); systemic anaplastic large cell lymphoma (systemic ALCL); angioimmunoblastic T-cell lymphoma (AITL): initial presentation

1st line – brentuximab vedotin + CHP, or CHOP, or CHOEP, or EPOCH

Back

1st line –

brentuximab vedotin + CHP, or CHOP, or CHOEP, or EPOCH

Treatment for peripheral T-cell lymphomas (including EATL, PTCL NOS, systemic ALCL, AITL) is based on histology (CD30 expression), stage, and patient factors (e.g., age, fitness, comorbidities).[135] Many patients are unsuitable for chemotherapy because of poor performance status.[136]

Enrollment in a clinical trial should be considered.

Preferred first-line treatments include: brentuximab vedotin plus CHP (cyclophosphamide, doxorubicin, and prednisone) if CD30+ histology confirmed; CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone); CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone); dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin).[49]

Patients who are unfit for chemotherapy are managed with the aim of palliation of symptoms.

See local specialist protocol for dosing guidelines.

Primary options

Brentuximab vedotin + CHP

brentuximab vedotin

and

cyclophosphamide

and

doxorubicin

and

prednisone

CHOP

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

CHOEP

cyclophosphamide

and

doxorubicin

and

vincristine

and

etoposide

and

prednisone

EPOCH

etoposide

and

prednisone

and

vincristine

and

cyclophosphamide

and

doxorubicin

Consider – radiation therapy

Back

Consider –

radiation therapy

Treatment recommended for SOME patients in selected patient group

Involved-site radiation therapy (ISRT) may be combined with first-line treatment regimens in certain patients (e.g., those with localized [stage I-II] disease).[49]

Consider – autologous stem cell transplant

Back

Consider –

autologous stem cell transplant

Treatment recommended for SOME patients in selected patient group

Eligible patients in complete remission following initial therapy may be considered for autologous stem cell transplant (ASCT).[49][137] However, the benefits of ASCT in peripheral T-cell lymphoma are unclear, and may be limited to certain subtypes.[138][139][140][141]

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Mesna is not required for less intensive cyclophosphamide-containing regimens (e.g., CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone], CHOEP [cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone]).

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

1st line – targeted therapy or chemotherapy

Back

1st line –

targeted therapy or chemotherapy

Recommended second-line and subsequent treatments for patients with relapsed or refractory disease include: belinostat, brentuximab vedotin (if not used previously and CD30+ histology confirmed), duvelisib, pralatrexate, or romidepsin.[49]

See local specialist protocol for dosing guidelines.

Primary options

belinostat

brentuximab vedotin

duvelisib

pralatrexate

romidepsin

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

subcutaneous panniculitis-like peripheral T-cell lymphoma; with hemophagocytic lymphohistiocytosis, systemic disease, or high tumor burden

1st line – cyclosporine ± prednisone, or pralatrexate ± prednisone, or romidepsin ± prednisone, or CHOEP, or EPOCH, or ESHA + cisplatin or oxaliplatin, or ICE

Back

1st line –

cyclosporine ± prednisone, or pralatrexate ± prednisone, or romidepsin ± prednisone, or CHOEP, or EPOCH, or ESHA + cisplatin or oxaliplatin, or ICE

Optimal management of subcutaneous panniculitis-like peripheral T-cell lymphoma (SPTCL) is unclear due to lack of evidence.

Treatment can be guided by the presence of hemophagocytic lymphohistiocytosis (HLH) and tumor burden.[49]

The following regimens can be considered for first-line treatment of patients with HLH, systemic disease, or high tumor burden: cyclosporine (with or without prednisone); pralatrexate (with or without prednisone); romidepsin (with or without prednisone); CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone); dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin); ESHA (etoposide, methylprednisolone, and cytarabine) plus a platinum agent (cisplatin or oxaliplatin); or ICE (ifosfamide, carboplatin, and etoposide).[49]

See local specialist protocol for dosing guidelines.

Primary options

cyclosporine modified

and

prednisone

pralatrexate

and

prednisone

romidepsin

and

prednisone

CHOEP

cyclophosphamide

and

doxorubicin

and

vincristine

and

etoposide

and

prednisone

EPOCH

etoposide

and

prednisone

and

vincristine

and

cyclophosphamide

and

doxorubicin

ESHA + platinum agent

etoposide

and

methylprednisolone

and

cytarabine

-- AND --

cisplatin

oxaliplatin

ICE

ifosfamide

and

carboplatin

and

etoposide

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide or ifosfamide should receive mesna to prevent hemorrhagic cystitis.

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

subcutaneous panniculitis-like peripheral T-cell lymphoma; without hemophagocytic lymphohistiocytosis, and low tumor burden (localized or limited subcutaneous disease)

1st line – cyclosporine ± prednisone, or methotrexate ± prednisone, or bexarotene ± prednisone, or local therapy

Back

1st line –

cyclosporine ± prednisone, or methotrexate ± prednisone, or bexarotene ± prednisone, or local therapy

Optimal management of subcutaneous panniculitis-like peripheral T-cell lymphoma (SPTCL) is unclear due to lack of evidence.

Treatment can be guided by the presence of hemophagocytic lymphohistiocytosis (HLH) and tumor burden.[49]

The following options can be considered for first-line treatment for patients without HLH who have low tumor burden (localized or limited subcutaneous disease): cyclosporine (with or without prednisone); methotrexate (with or without prednisone); bexarotene (with or without prednisone); or local therapy (involved-site radiation therapy [ISRT] or intralesional corticosteroid).[49]

See local specialist protocol for dosing guidelines.

Primary options

cyclosporine modified

and

prednisone

methotrexate

and

prednisone

bexarotene

and

prednisone

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

indolent B-cell lymphomas

classic follicular lymphoma; stage I or II: initial presentation

1st line – radiation therapy, rituximab, or observation

Back

1st line –

radiation therapy, rituximab, or observation

Treatment for classic follicular lymphoma (cFL) is based on stage, indications for treatment (including: symptoms; threatened end-organ function; clinically significant/progressive cytopenia secondary to lymphoma; clinically significant bulky diseases; steady/rapid progression), and patient factors (e.g., age, fitness, comorbidities).[48]

Prognostic tools (e.g., Follicular Lymphoma International Prognostic Index [FLIPI]) can help guide treatment. See Criteria.

Initial therapy for localized (stage I or II) disease includes involved-site radiation therapy and/or single-agent rituximab (with or without chemotherapy).[48][142]

Observation may be considered for some patients (e.g., those with noncontiguous stage II disease in whom toxicity of treatment outweighs benefit).

Consolidation with rituximab may be considered for patients who respond to initial treatment with rituximab alone.[48]

See local specialist protocol for dosing guidelines.

Primary options

rituximab

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

classic follicular lymphoma; stage III or IV: initial presentation

1st line – observation, or rituximab, or chemotherapy ± rituximab or obinutuzumab, or lenalidomide + rituximab

Back

1st line –

observation, or rituximab, or chemotherapy ± rituximab or obinutuzumab, or lenalidomide + rituximab

Observation is recommended for patients with advanced-stage disease (stage III or IV) who have no indication for treatment.[48]

For patients with advanced-stage disease who have a high tumor burden and indications for treatment, the preferred first-line treatment regimens include: CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus obinutuzumab or rituximab; bendamustine plus rituximab or obinutuzumab; CVP (cyclophosphamide, vincristine, and prednisone) plus obinutuzumab or rituximab; lenalidomide plus rituximab.[48][143][144][145][146]

The preferred first-line treatment for patients with low tumor burden and indications for treatment is rituximab alone.[48]

In older patients and/or those with significant comorbidities, rituximab alone may be a good palliative choice if treatment is indicated.[48] Chlorambucil (with or without rituximab) or cyclophosphamide (with or without rituximab) may also be considered for these patients.

Consolidation with rituximab may be considered for patients who respond to initial treatment with rituximab alone.[48]

Maintenance therapy with rituximab or obinutuzumab may be considered for patients who respond to chemoimmunotherapy (depending on the initial regimen used and response achieved).[48]

See local specialist protocol for dosing guidelines.

Primary options

rituximab

obinutuzumab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

bendamustine

and

rituximab

bendamustine

and

obinutuzumab

lenalidomide

and

rituximab

obinutuzumab

and

cyclophosphamide

and

vincristine

and

prednisone

rituximab

and

cyclophosphamide

and

vincristine

and

prednisone

chlorambucil

and

rituximab

cyclophosphamide

and

rituximab

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Older patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

classic follicular lymphoma; relapsed/progressive/refractory disease

1st line – observation or chemotherapy or targeted therapy or immunotherapy

Back

1st line –

observation or chemotherapy or targeted therapy or immunotherapy

Patients with relapsed or progressive disease who have no indications for treatment can be observed.[48]

Patients with relapsed, progressive, or refractory disease who have indications for treatment can be considered for second-line treatments.

Second-line options include (if not used previously): CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) plus obinutuzumab or rituximab; CVP (cyclophosphamide, vincristine, and prednisone) plus obinutuzumab or rituximab; bendamustine plus rituximab or obinutuzumab, lenalidomide with or without rituximab; lenalidomide plus obinutuzumab; obinutuzumab alone; rituximab alone.[48]

In patients previously exposed to chemotherapy and monoclonal antibody therapy, lenalidomide plus monoclonal antibody would be a standard second-line therapy.

Rituximab alone may be a good palliative choice for older patients and/or those with significant comorbidities.[48] Tazemetostat or cyclophosphamide (with or without rituximab) may also be considered for these patients.

Maintenance therapy with rituximab or obinutuzumab, or consolidation therapy with autologous stem cell transplant (ASCT), may be considered for those who respond to second-line treatment.[48]

Third-line and subsequent treatment options include: bispecific antibody therapy (epcoritamab; mosunetuzumab); CAR T-cell therapy (axicabtagene ciloleucel; lisocabtagene maraleucel; tisagenlecleucel); tazemetostat; or zanubrutinib plus obinutuzumab.

Second-line treatments can also be considered for third-line use if not previously used.

See local specialist protocol for dosing guidelines.

Primary options

obinutuzumab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

obinutuzumab

and

cyclophosphamide

and

vincristine

and

prednisone

rituximab

and

cyclophosphamide

and

vincristine

and

prednisone

bendamustine

and

rituximab

bendamustine

and

obinutuzumab

rituximab

obinutuzumab

lenalidomide

and

rituximab

lenalidomide

and

obinutuzumab

tazemetostat

cyclophosphamide

and

rituximab

Secondary options

tisagenlecleucel

lisocabtagene maraleucel

axicabtagene ciloleucel

epcoritamab

mosunetuzumab

zanubrutinib

and

obinutuzumab

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Older patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

marginal zone lymphoma; nodal

1st line – radiation therapy; or radiation therapy + rituximab ± chemotherapy; or rituximab ± chemotherapy

Back

1st line –

radiation therapy; or radiation therapy + rituximab ± chemotherapy; or rituximab ± chemotherapy

Initial treatment options include: involved-site radiation therapy (ISRT); ISRT plus rituximab (with or without chemotherapy); or rituximab (with or without chemotherapy).[48]

Recommended chemotherapy regimens include bendamustine, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), CVP (cyclophosphamide, vincristine, and prednisone), or lenalidomide.[48]

See local specialist protocol for dosing guidelines.

Primary options

rituximab

and

bendamustine

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

rituximab

and

cyclophosphamide

and

vincristine

and

prednisone

rituximab

and

lenalidomide

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Older patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

2nd line – chemotherapy or targeted therapy or immunotherapy

Back

2nd line –

chemotherapy or targeted therapy or immunotherapy

Second-line and subsequent treatment options include (if not used previously): bendamustine plus obinutuzumab (not recommended if treated with prior bendamustine); bendamustine plus rituximab (not recommended if treated with prior bendamustine); acalabrutinib; zanubrutinib (after at least one prior anti-CD20 monoclonal antibody-based regimen); pirtobrutinib (after prior covalent BTK inhibitor therapy); CHOP plus rituximab; CVP plus rituximab; lenalidomide plus rituximab.

Axicabtagene ciloleucel is a third-line therapy for patients with MZL.[48]

See local specialist protocol for choice of regimen and dosing guidelines.

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Older patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

marginal zone lymphoma; splenic

1st line – hepatitis C treatment or rituximab or splenectomy or observation

Back

1st line –

hepatitis C treatment or rituximab or splenectomy or observation

Initial treatment options include: hepatitis C treatment (if hepatitis C positive), rituximab, splenectomy, or observation (e.g., if asymptomatic and/or without splenomegaly).[48][148][149]

See local specialist protocol for dosing guidelines.

Primary options

rituximab

2nd line – chemotherapy or targeted therapy or immunotherapy

Back

2nd line –

chemotherapy or targeted therapy or immunotherapy

Second-line and subsequent treatment options include (if not used previously): bendamustine plus obinutuzumab (not recommended if treated with prior bendamustine); bendamustine plus rituximab (not recommended if treated with prior bendamustine); acalabrutinib; zanubrutinib (after at least one prior anti-CD20 monoclonal antibody-based regimen); pirtobrutinib (after prior covalent BTK inhibitor therapy); CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) plus rituximab; CVP (cyclophosphamide, vincristine, and prednisone) plus rituximab; lenalidomide plus rituximab.

Axicabtagene ciloleucel is a third-line therapy for patients with MZL.[48]

See local specialist protocol for choice of regimen and dosing guidelines.

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Older patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF).[154][155]

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

marginal zone lymphoma; Helicobacter pylori-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma

1st line – H pylori eradication

Back

1st line –

H pylori eradication

Gastric MALT lymphoma is commonly associated with H pylori infection.

Initial treatment for H pylori-positive gastric MALT is with antibiotics to eradicate H pylori.[48]

For more detail on H pylori eradication therapy see MALT lymphoma.

marginal zone lymphoma; antibiotic-resistant gastric mucosa-associated lymphoid tissue (MALT) lymphoma

1st line – radiation therapy or rituximab

Back

1st line –

radiation therapy or rituximab

Patients who have the t(11;18) translocation are often H pylori-negative, and have antibiotic-resistant tumors.[150]

Initial treatment options for antibiotic-resistant gastric MALT lymphoma (i.e., H pylori-negative or t(11;18)-positive) include involved-site radiation therapy (ISRT) or rituximab (if ISRT is contraindicated).[48]

For more detail see MALT lymphoma.

See local specialist protocol for dosing guidelines.

Primary options

rituximab

Consider – H pylori eradication

Back

Consider –

H pylori eradication

Treatment recommended for SOME patients in selected patient group

Patients who are t(11;18)-positive and H pylori-positive can be treated with antibiotics (in addition to ISRT or rituximab) to eradicate the underlying H pylori infection.[48]

primary cutaneous B-cell lymphoma (primary cutaneous follicle center lymphoma and primary cutaneous marginal zone lymphoma)

1st line – surgery, or radiation therapy, or rituximab ± chemotherapy

Back

1st line –

surgery, or radiation therapy, or rituximab ± chemotherapy

Treatment options for localized primary cutaneous follicle center lymphoma (PCFL) or primary cutaneous marginal zone lymphoma (PCMZL) include: local involved-site radiation therapy (ISRT) or surgical resection (for small isolated lesions).[54]

Patients with generalized disease or cosmetically disfiguring lesions may require systemic treatment (e.g., rituximab with or without CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]).[54]

See local specialist protocol for dosing guidelines.

Primary options

rituximab

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

primary cutaneous B-cell lymphoma (primary cutaneous diffuse large B-cell lymphoma, leg type)

1st line – R-CHOP ± radiation therapy, or radiation therapy (palliative)

Back

1st line –

R-CHOP ± radiation therapy, or radiation therapy (palliative)

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, leg type) is associated with an aggressive clinical course and poor survival.

Recommended first-line treatments for younger and fit older patients with PCDLBCL, leg type include: R-CHOP plus involved-site radiation therapy (ISRT) for localized disease, R-CHOP with or without ISRT for generalized disease.[48]

In older patients or patients with significant comorbidities, palliative radiation therapy for localized lesions can be utilized.[48][151]

See local specialist protocol for dosing guidelines.

Primary options

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

Consider – CNS prophylaxis

Back

Consider –

CNS prophylaxis

Treatment recommended for SOME patients in selected patient group

CNS prophylaxis may be considered for patients with PCDLBCL, leg type due to the increased risk for CNS relapse with this subtype.[48]

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

indolent T-cell lymphomas

primary cutaneous anaplastic large cell lymphoma; with solitary or grouped lesions

1st line – radiation therapy, or surgical excision ± radiation therapy

Back

1st line –

radiation therapy, or surgical excision ± radiation therapy

Treatments for localized disease (solitary or grouped lesions) include involved-site radiation therapy (ISRT), or surgical excision with or without ISRT (for small local lesions).[54]

primary cutaneous anaplastic large cell lymphoma; with multifocal lesions or regional lymph node involvement

1st line – brentuximab vedotin

Back

1st line –

brentuximab vedotin

Brentuximab vedotin is the preferred initial treatment for patients with multifocal lesions or regional lymph node involvement.[54]

See local specialist protocol for dosing guidelines.

Primary options

brentuximab vedotin

Consider – radiation therapy

Back

Consider –

radiation therapy

Treatment recommended for SOME patients in selected patient group

If patients have regional lymph node involvement, involved-site radiation therapy (ISRT) may be combined with brentuximab vedotin, or used alone in select patients.[54]

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

breast implant-associated anaplastic large cell lymphoma; localized disease

1st line – surgery

Back

1st line –

surgery

Treatment for localized disease (i.e., confined to the fibrous scar capsule) is complete surgical resection of the breast implant, capsule, and associated mass.[49] Suspicious lymph nodes detected during explantation should be biopsied.

Removal of the contralateral breast implant can be considered because bilateral disease is reported in approximately 4.6% of cases.[49][152]

Re-excision surgery alone (without systemic therapy) may be possible for local disease relapse.[49]

The FDA recommends that cases of breast implant-associated anaplastic large cell lymphoma should be reported to a national disease registry (e.g., PROFILE Registry).[153]

breast implant-associated anaplastic large cell lymphoma; advanced disease

1st line – brentuximab vedotin with or without CHP, or CHOP, or CHOEP, or EPOCH

Back

1st line –

brentuximab vedotin with or without CHP, or CHOP, or CHOEP, or EPOCH

Patients with advanced-stage breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) may be considered for systemic therapy, including: brentuximab vedotin (an anti-CD30 antibody-drug conjugate) with or without CHP (cyclophosphamide, doxorubicin, and prednisone); CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone); CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone); dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin).[49]

The FDA recommends that cases of BIA-ALCL should be reported to a national disease registry (e.g., PROFILE Registry).[153]

See local specialist protocol for dosing guidelines.

Primary options

brentuximab vedotin

Brentuximab vedotin + CHP

brentuximab vedotin

and

cyclophosphamide

and

doxorubicin

and

prednisone

CHOP

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisone

CHEOP

cyclophosphamide

and

doxorubicin

and

vincristine

and

etoposide

and

prednisone

EPOCH

etoposide

and

prednisone

and

vincristine

and

cyclophosphamide

and

doxorubicin

Consider – supportive care

Back

Consider –

supportive care

Treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent hemorrhagic cystitis.

Antimicrobial prophylaxis may be considered if severe neutropenia (absolute neutrophil count <500 cells/microliter [<0.5 × 10⁹/L]).

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Non-Hodgkin lymphoma

Treatment algorithm

aggressive B-cell lymphomas

R-CHOP-21 ± radiation therapy

Primary options

R-CHOP-21

supportive care

CNS prophylaxis

Primary options

R-CHOP-21 ± radiation therapy

Primary options

R-CHOP-21

supportive care

CNS prophylaxis

Primary options

R-CHOP-21 or Pola-R-CHP

Primary options

R-CHOP-21

Pola-R-CHP

supportive care

CNS prophylaxis

Primary options

R-CHOP-21 or Pola-R-CHP or R-EPOCH

Primary options

R-CHOP-21

Pola-R-CHP

Secondary options

R-EPOCH

supportive care

CNS prophylaxis

Primary options

chimeric antigen receptor (CAR) T-cell therapy or salvage chemotherapy

Primary options

Secondary options

DHA + platinum agent

DHA + platinum agent + rituximab

ICE

ICE + rituximab

supportive care

chimeric antigen receptor (CAR) T-cell therapy or bispecific antibody therapy or loncastuximab tesirine or selinexor

Primary options

supportive care

salvage chemotherapy

Primary options

DHA + platinum agent

DHA + platinum agent + rituximab

ICE

ICE + rituximab

autologous stem cell transplant ± radiation therapy, or chimeric antigen receptor (CAR) T-cell therapy

Primary options

supportive care

chimeric antigen receptor (CAR) T-cell therapy or bispecific antibody therapy or loncastuximab tesirine or selinexor

Primary options

supportive care

chimeric antigen receptor (CAR) T-cell therapy or monoclonal antibody therapy or salvage chemotherapy

Primary options

CEOP

CEOP + rituximab

EPOCH

EPOCH + rituximab

GemOx

GemOx + rituximab

supportive care

chimeric antigen receptor (CAR) T-cell therapy or bispecific antibody therapy or loncastuximab tesirine or selinexor

Primary options

supportive care

chemotherapy ± radiation therapy

Primary options

R-EPOCH

R-CHOP-21

Secondary options

ICE

ICE + rituximab

supportive care

pembrolizumab, or nivolumab ± brentuximab vedotin

Primary options

supportive care

methotrexate-based chemotherapy ± consolidation therapy

Primary options

R-MPV