Emerging treatments

Venetoclax

Venetoclax is an oral B-cell lymphoma-2 (BCL-2) inhibitor. In a phase 2 trial of 30 patients with previously treated WM, venetoclax had an overall response rate of 87%.[108] Severe neutropenia occurred in 13.3% of patients.[108]

Daratumumab

Daratumumab is an anti-CD38 monoclonal antibody. It has been used extensively in multiple myeloma, and is undergoing clinical trials in WM given its likely efficacy and tolerability.[109][110]

Everolimus

Everolimus is a mammalian target of rapamycin (mTOR) inhibitor. In a phase 2 trial of 60 patients with relapsed/refractory WM, everolimus had an overall response rate of 50% (all were partial response), and median progression-free survival was 21 months.[111] In a phase 2 trial of 33 patients with symptomatic untreated WM, everolimus had an overall response rate of 72.7%.[112] Pneumonitis occurred in 6 patients, with 3 patients requiring hospitalisation.[112]

Perifosine

Perifosine is a novel alkylphospholipid Akt inhibitor. In a phase 2 trial of 37 patients with relapsed/refractory WM, perifosine had a partial response rate of 11%.[113] Other studies have reported an overall response rate of 36%.[114]

Panobinostat

Panobinostat is a histone deacetylase (HDAC) inhibitor. In a phase 2 trial of 39 patients with relapsed/refractory WM, panobinostat had an overall response rate of 47%.[115]

Ofatumumab

Ofatumumab is a fully human anti-CD20 monoclonal antibody. In a phase 2 trial of 37 patients with WM (28 patients with relapsed/refractory WM), ofatumumab had an overall response rate of 32%.[116]

Pentostatin plus cyclophosphamide and rituximab

Pentostatin is an antimetabolite chemotherapy agent. In a phase 2 trial of 25 patients with WM, pentostatin plus cyclophosphamide and rituximab had a 2-year progression-free survival rate of 83.6% and a 2-year overall survival rate of 100% in those with untreated WM (n=21).[117]

Pirtobrutinib

​Pirtoburinib, a non-covalent third-generation Bruton’s tyrosine kinase (BTK) inhibitor, has demonstrated promising activity and good tolerability in the phase 1/2 BRUIN trial of patients with relapsed low-grade B-cell non-Hodgkin’s lymphoma, that also included patients with relapsed WM previously treated with BTK inhibitors.[118]

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