Blinatumomab
Bispecific antibodies can recognize two different antigens simultaneously. Blinatumomab, an anti-CD19/-CD3 bispecific antibody (approved by the Food and Drug Administration [FDA] in the setting of B-cell precursor acute lymphoblastic leukemia) has shown promising anti-lymphoma activity as a salvage strategy in relapsed/refractory NHL.[164]Goebeler ME, Knop S, Viardot A, et al. Bispecific T-cell engager (BiTE) antibody construct blinatumomab for the treatment of patients with relapsed/refractory non-Hodgkin lymphoma: final results from a phase I study. J Clin Oncol. 2016 Apr 1;34(10):1104-11.
https://www.doi.org/10.1200/JCO.2014.59.1586
http://www.ncbi.nlm.nih.gov/pubmed/26884582?tool=bestpractice.com
[165]Viardot A, Goebeler ME, Hess G, et al. Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma. Blood. 2016 Mar 17;127(11):1410-6.
https://www.doi.org/10.1182/blood-2015-06-651380
http://www.ncbi.nlm.nih.gov/pubmed/26755709?tool=bestpractice.com
Lutetium (177Lu)-satetraxetan-lilotomab
177Lu-satetraxetan-lilotomab is an antibody conjugated to a low-intensity radionuclide (lutetium-177) that targets CD37, which is found on most B-cell lymphomas.[166]Kolstad A, Madsbu U, Beasley M, et al. 177 lu-lilotomab satetraxetan, a novel CD37-targeted antibody-radionuclide conjugate in relapsed non-Hodgkin's lymphoma (NHL): updated results of an ongoing phase I/II study (LYMRIT 37-01). 59th ASH Annual Meeting abstracts. 623: mantle cell, follicular, and other indolent b-cell lymphoma - clinical studies: poster II. Blood. 2017 Dec 7;130(Suppl 1):2769.
https://ashpublications.org/blood/article/130/Supplement%201/2769/80417/177-Lu-Lilotomab-Satetraxetan-a-Novel-CD37
[167]Kolstad A, Madsbu U, Beasley M, et al. LYMRIT 37-01: a phase I/II study of 177lu-lilotomab satetraxetan (Betalutin®) antibody-radionuclide-conjugate (ARC) for the treatment of relapsed non-Hodgkin's lymphoma (NHL) - analysis with 6-month follow-up. 60th ASH Annual Meeting abstracts. 623: mantle cell, follicular, and other indolent b-cell lymphoma - clinical studies: poster II. Blood. 2018 Nov 29;132(Suppl 1):2879.
https://ashpublications.org/blood/article/132/Supplement%201/2879/263950/LYMRIT-37-01-A-Phase-I-II-Study-of-177lu-Lilotomab
It has been granted FDA fast-track designation for relapsed or refractory follicular lymphoma after at least two prior systemic therapies. In the UK, 177Lu-satetraxetan-lilotomab has also been granted Promising Innovative Medicine designation by the Medicines and Healthcare products Regulatory Agency for this indication.
BCL2 inhibitors
Venetoclax is a selective oral BCL2 inhibitor that is being evaluated in various subtypes of NHL[168]Tam CS, Anderson MA, Pott C, et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018 Mar 29;378(13):1211-23.
https://www.nejm.org/doi/10.1056/NEJMoa1715519
http://www.ncbi.nlm.nih.gov/pubmed/29590547?tool=bestpractice.com
[169]Parikh A, Gopalakrishnan S, Freise KJ, et al. Exposure-response evaluations of venetoclax efficacy and safety in patients with non-Hodgkin lymphoma. Leuk Lymphoma. 2018 Apr;59(4):871-9.
http://www.ncbi.nlm.nih.gov/pubmed/28797193?tool=bestpractice.com
Baltaleucel-T (CMD-003)
A cell-based immunotherapy comprising a preparation of autologous Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes, which have specific reactivity to EBV antigens. Baltaleucel-T targets and binds to EBV-expressing cancer cells specifically expressing the targeted antigens. It is being investigated for its effect on EBV-expressing lymphomas, including natural killer T-cell lymphomas and post-transplant lymphoproliferative disorders.[170]Kim WS, Oki Y, Kim SJ, et al. Autologous EBV-specific T cell treatment results in sustained responses in patients with advanced extranodal NK/T lymphoma: results of a multicenter study. Ann Hematol. 2021 Oct;100(10):2529-39.
http://www.ncbi.nlm.nih.gov/pubmed/34304287?tool=bestpractice.com
Nanatinostat plus valganciclovir
Nanatinostat (an oral histone deacetylase inhibitor) in combination with the antiviral valganciclovir has been granted orphan drug designation by the FDA for the treatment of angioimmunoblastic T-cell lymphoma and Epstein Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified (EBV+ DLBCL, NOS). Nanatinostat is designed to activate EBV genes that have been epigenetically suppressed.[171]ClinicalTrials.gov. Dose escalation and expansion study of orally administered VRx-3996 and valganciclovir in subjects with Epstein-Barr virus-associated lymphoid malignancies. Jul 2021 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03397706
[172]Porcu P, Haverkos B, Brem E, et al. A phase Ib/II study of oral nanatinostat (N) and valganciclovir (VG) in subjects with Epstein-Barr virus (EBV)-associated lymphomas. 2019 ASCO Annual Meeting I. Hematologic malignancies - lymphoma and chronic lymphocytic leukemia. Abstract 7551. J Clin Oncol. 2019 May 20;37(15 Suppl):7551.
https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.7551
Chidamide
An orally active benzamide-type histone deacetylase inhibitor. Investigated as a constituent agent of conditioning therapy for high-risk or relapsed/refractory NHL.[173]Ji J, Liu Z, Kuang P, et al. A new conditioning regimen with chidamide, cladribine, gemcitabine and busulfan significantly improve the outcome of high-risk or relapsed/refractory non-Hodgkin's lymphomas. Int J Cancer. 2021 Dec 15;149(12):2075-82.
https://www.doi.org/10.1002/ijc.33761
http://www.ncbi.nlm.nih.gov/pubmed/34398971?tool=bestpractice.com