The global, open-label, single-arm, phase II MAGNOLIA trial was designed to assess the next-generation BTK inhibitor zanubrutinib in patients with relapsed/refractory marginal zone lymphoma (MZL) who had previously received ≥ 1 CD20-directed regimen. After a median follow-up of 15.7 months, the overall response rate (ORR) according to independent review was 68.2 %, with complete remissions resulting in 25.8 %.
Recurrent follicular lymphoma (FL) and marginal zone lymphoma (MZL) are treated similarly, mostly with single-agent rituximab. In patients with relapsed/refractory FL, the combination of lenalidomide with rituximab (R2) has previously demonstrated promising efficacy. The multicenter, double-blind, randomized, phase III AUGMENT study was initiated to compare time-limited treatment for approximately one year with R2 vs. rituximab plus placebo in patients with FL grade I-IIIa or MZL who had already received ≥ 1 prior systemic chemotherapy, immunotherapy or chemoimmunotherapy but who were not refractory to rituximab.
Advanced-stage follicular lymphoma (FL) remains incurable, with most patients eventually experiencing disease progression despite therapeutic advances. Relapsed or refractory FL is challenging to treat, particularly in high-risk patients who are refractory to prior treatments and have progressed within 24 months. The combination of rituximab and lenalidomide (R2) is commonly used in this setting, although complete response (CR) rates are suboptimal.
Approximately one third of patients with diffuse large B-cell lymphoma (DLBCL) develop relapsed or refractory disease, which remains a major cause of mortality. In patients relapsing more than 1 year after first-line treatment, the standard of care is salvage treatment followed by autologous stem cell transplantation (ASCT), although responses to platinum-based salvage therapy are generally suboptimal.
The first-in-class, covalent BTK inhibitor ibrutinib has transformed the treatment of patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). However, toxicities frequently lead to treatment discontinuation. Moreover, exposure coverage between dosing intervals falls below the IC50 threshold, and BTK occupancy at trough levels is variable.
Venetoclax 400 mg QD in combination with azacitidine 75 mg/m2 on days 1–7 has been approved for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy based on the phase III VIALE-A trial that met its primary endpoint of overall survival (OS) at the time of the interim analysis conducted in March 2020.
The initial treatment of patients with mantle-cell lymphoma (MCL) is continuously evolving due to the introduction of new targeted agents. Ruan et al. conducted a single-arm phase II study based on the hypothesis that the addition of the next-generation BTK inhibitor acalabrutinib to lenalidomide plus rituximab (ALR) would synergize activity and accelerate minimal residual disease (MRD)-negative complete response (CR), thus allowing for response-adapted adjustment of treatment intensity to minimize toxicity.
Although covalent BTK inhibitors are increasingly important in the management of patients with Waldenström’s macroglobulinemia (WM), progression and intolerance frequently necessitate treatment discontinuation. In the relapsed/refractory setting, the therapeutic options following chemoimmunotherapy and covalent BTK inhibitor therapy are limited, with no accepted standard of care.
The 64th Annual Meeting of the American Society of Hematology (ASH) took place as a hybrid event that hosted participants both online and on-site in New Orleans, Louisiana, USA. Among the multitude of updates and new insights presented from December 10th to 13th, 2022, attendees had access to thousands of scientific abstracts highlighting cutting-edge research in hematology.
