Lymphoma
Updates on BTK- and Bcl-2–targeted treatment in various B-cell malignancies
Updates on BTK- and Bcl-2–targeted treatment in various B-cell malignancies Ibrutinib plus CIT: SELENE trial Survival outcomes typically deteriorate with repeated lines of chemoimmunotherapy (CIT) in patients with relapsed/refractory non-Hodgkin lymphoma. The randomized, double-blind phase III ...
DLBCL: treatment of elderly patients and relapsed disease
Overall survival has improved considerably in the setting of diffuse large B-cell lymphoma (DLBCL). However, patients above the age of 80 years are an exception in terms of survival prolongation and therefore face an unmet clinical need [1]. At the same time, this is a group that constitutes an increasing proportion of DLBCL patients.
Waldenström macroglobulinemia: findings from ASPEN and BRUIN
In the management of patients with Waldenström macroglobulinemia (WM), BTK inhibitors have changed the therapeutic landscape and are considered preferred treatment options for the first and later lines. Compared to the first-in-class agent ibrutinib, the potent and irreversible BTK inhibitor zanubrutinib offers improved BTK selectivity that minimizes off-target effects and toxicities.
Follicular lymphoma: study results with bispecific antibodies and BTK inhibitors
Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL) subtype [1]. In general, it remains incurable with standard therapies, and most patients experience multiple relapses over time. Therefore, there remains a great need for innovative new regimens such as the first-in-class CD20xCD3 T-cell–engaging bispecific antibody mosunetuzumab that is being tested in a pivotal phase II trial in patients with relapsed/refractory grade 1-3a FL after ≥ 2 lines of therapy (including an anti-CD20 antibody and an alkylating agent).
Current insights into BTK inhibition and other targeted approaches in CLL
In the setting of early-stage, asymptomatic chronic lymphocytic leukemia (CLL), the concept of watch & wait in the era of targeted agents was challenged by the placebo-controlled, double-blind, phase III CLL12 study. This trial assessed the use of ibrutinib 420 mg OD (n = 182) vs. placebo (n = 181) until symptomatic disease progression in treatment-naïve patients with asymptomatic CLL Binet stage A who had an increased risk due to factors such as del(17p), IGHV mutation status, or age.
Final analysis of the MAGNOLIA trial: zanubrutinib in marginal zone lymphoma
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 %.
Clinical findings with sundry targets in various B-cell malignancies
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.
Follicular lymphoma: bispecific and PI3Kδ-targeted approaches
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.
