Lymphoma
Updated findings in CLL with a focus on BTK- and Bcl-2–targeted therapies
Personalization of treatment duration of ibrutinib plus venetoclax using measurable residual disease (MRD) was explored in fit patients with previously untreated chronic lymphocytic leukemia (CLL) in the multicenter, randomized, open-label, phase III FLAIR trial. At ASH 2023, Hillmen et al. presented the results for the comparison of ibrutinib plus venetoclax (n = 260) with 6 cycles of fludarabine, cyclophosphamide, and rituximab (FCR; n = 263).
Follicular lymphoma: BTK inhibition and bispecific antibodies
With respect to the treatment of newly diagnosed follicular lymphoma (FL), there is room for improvement as many patients relapse after first-line chemoimmunotherapy. The frontline use of lenalidomide and rituximab (R2) has proven highly active in patients with FL. A single-arm phase II study investigated the addition of the BTK inhibitor acalabrutinib to R2 in patients with untreated FL based on the hypothesis that this combination will increase efficacy due to beneficial effects on the immune microenvironment.
Waldenström macroglobulinemia: optimizing outcomes in the first and later lines
Th e randomized phase III ASPEN study compared the next-generation BTK inhibitor zanubrutinib with ibrutinib in patients with symptomatic, MYD88-mutated Waldenström macroglobulinemia (WM), demonstrating a trend towards better response quality and decreased toxicity in the zanubrutinib arm. Eligible patients who participated in trials of zanubrutinib for the treatment of B-cell malignancies could enroll in the BGB-3111-LTE1 study.
Mantle cell lymphoma: emerging treatment regimens and new standards
Based on promising results of early-phase studies, the multinational, double-blind, placebo-controlled phase III SYMPATICO trial is evaluating the concurrent administration of the BTK inhibitor ibrutinib and the Bcl-2 inhibitor venetoclax in the setting of relapsed/refractory mantle cell lymphoma (MCL). Patients after 1–5 prior therapies who had received ≥ 1 rituximab/anti-CD20-containing regimen were randomized to either ibrutinib plus venetoclax (n = 134) or ibrutinib plus placebo (n = 133).
Interview: Different perspectives on how to define success in CLL
Fortunately, the landscape of CLL treatment has dramatically transformed over the last ten years, shifting from chemotherapy to new targeted therapies. These advancements have not only extended patients' lifespans but also often enhanced their quality of life. Consequently, many patients now undergo continuous treatment throughout their lives and frequently pass away from causes unrelated to CLL. At this year’s iwCLL, there was a debate and roundtable on how to define success in CLL. From a physician's perspective, how is success in CLL treatment defined?
Issues in the management of CLL patients from an international point of view
The CLL Advocates Network (CLLAN) is a global network of patient advocacy organizations dedicated to improving the outcomes of patients with CLL through collaboration with national organizations. Principles guiding the work of CLLAN include the support of local communities, sharing of best practices and advocacy for better care and access.
CLL treatment in the real world: insights from across the globe
The analysis reported by Davids et al. at iwCLL 2023 examined the characteristics, treatment patterns and outcomes of a cohort of 1,102 real-world US patients with CLL receiving two or more lines of therapy. Data were obtained from the COTA real-world database. Second-line treatment was initiated between 2014 and 2021.
Overcoming resistance to targeted inhibitors
As covalent BTK inhibitors have been in use for the treatment of CLL in clinical practice for an extended period of time, different resistance mutations are being observed. Dr. Adrian Wiestner, MD, PhD, National Institutes of Health, Bethesda, USA, noted that mutations at progression are variable depending on the specific BTK inhibitor used, with the “classical” C481 mutations prevailing on ibrutinib and acalatinib treatment, while L528W mutations are mainly found in the context of zanubrutinib therapy.