MCL Literature Feed

This case report details severe glofitamab-induced ICANS with seizures in a heavily pre-treated MCL patient, highlighting CNS risk factors and successful management with anakinra and antiseizure drugs.

Brexucabtagene autoleucel (CAR-T) combined with BTK inhibitors is a potentially safe and effective strategy for treating relapsed mantle cell lymphoma with central nervous system involvement.

Combining CAR-T therapy with a BTK inhibitor may offer a synergistic strategy to effectively treat mantle cell lymphoma with central nervous system involvement, a historically poor-prognosis population.

An indirect comparison suggests brexucabtagene autoleucel provides superior response rates and progression-free survival over pirtobrutinib for MCL patients who have failed a prior covalent BTKi.

The PI3Ki zandelisib plus BTKi zanubrutinib combination shows high efficacy (74% ORR, 47% CR) with manageable toxicity in relapsed/refractory MCL, offering a promising chemotherapy-free regimen.

This review provides a framework for integrating bispecific antibodies into MCL treatment, addressing the critical clinical question of how to sequence them with other novel immunotherapies like CAR-T.

This preclinical study identifies DNMT3A-mediated metabolic reprogramming to oxidative phosphorylation as a novel ibrutinib resistance mechanism, which can be overcome by low-dose decitabine.

This meta-analysis across B-NHLs confirms lenalidomide-based regimens improve OS and PFS, supporting its established role in relapsed/refractory and maintenance settings for MCL.

The CAR-T therapy lisocabtagene maraleucel demonstrates high, durable complete responses and a favorable safety profile in heavily pretreated, relapsed/refractory MCL, including high-risk patients.

This article summarizes Israeli national guidelines for administering CAR-T therapy in relapsed/refractory MCL, detailing patient management, toxicity monitoring for CRS and ICANS, and long-term follow-up principles.

Severe neurotoxicity after brexucabtagene autoleucel is common, associated with MRI/EEG changes and longer hospitalization, but importantly does not negatively impact treatment response or survival in MCL patients.

Palbociclib plus venetoclax shows preclinical synergy in ibrutinib-refractory MCL by downregulating MCL1, offering a chemo-free option for patients without RB1 deletion.

This review details BTK inhibitor resistance mechanisms, particularly C481S mutations, and highlights non-covalent BTKi (pirtobrutinib) and PROTACs as key strategies to overcome relapse in MCL.

Combining time-limited ibrutinib with CTL019 CAR-T in relapsed/refractory MCL achieved an 80% CR rate with manageable toxicity, showing efficacy even in BTKi-pretreated and TP53-mutated patients.

Single-cell analysis reveals the HSP90-MYC-CDK9 network drives sequential BTKi and CAR-T resistance, suggesting co-targeting HSP90 and CDK9 as a novel strategy for dual-refractory MCL.

This real-world study shows significant MCL-related mortality after first relapse (23%), suggesting high-risk patients may not survive to receive novel therapies, supporting their use in earlier lines.

Ibrutinib plus venetoclax shows high efficacy (83% CR) and deep MRD negativity with good tolerability in Japanese patients with relapsed/refractory MCL, supporting its use in this population.

This Japanese post-marketing surveillance study confirms the real-world efficacy (59.9% ORR) and safety of ibrutinib in heavily pre-treated, elderly patients with relapsed/refractory MCL, supporting its routine use.

This 2024 review of 80 FDA-approved kinase inhibitors highlights pirtobrutinib's recent approval for relapsed/refractory MCL, contextualizing its properties within the broader landscape of targeted therapies.

This Phase 1 study establishes the safety and recommended dose of a quadruplet regimen combining chemoimmunotherapy (BR) with dual targeted agents (ibrutinib, venetoclax) for relapsed/refractory MCL.

This retrospective study of 134 patients demonstrates that adding a BTK inhibitor to chemotherapy improves efficacy and prolongs progression-free survival in relapsed/refractory MCL.

An MRD-driven, finite-duration venetoclax-lenalidomide-rituximab regimen is effective in relapsed/refractory MCL, even post-BTKi, allowing nearly half of patients to stop therapy and maintain durable molecular remissions.

Pirtobrutinib, a non-covalent BTKi, gained FDA accelerated approval for MCL after prior BTKi failure, offering a 50% overall response rate for this high-unmet-need population.

Final overall survival data from a phase 2 trial confirm durable responses to acalabrutinib monotherapy in relapsed/refractory MCL, including in patients with poor prognostic features.

Radiation therapy is a feasible bridging strategy to control disease in relapsed/refractory MCL patients awaiting CAR-T infusion, potentially improving eligibility and outcomes for those with bulky disease.

Pirtobrutinib, the first approved non-covalent BTKi, offers a crucial new therapy for relapsed/refractory MCL by overcoming resistance mechanisms, including C481 mutations, from prior covalent BTK inhibitors.

This indirect comparison of ZUMA-2 (brexucabtagene autoleucel) and SCHOLAR-2 (standard of care) demonstrates a substantial overall survival benefit for CAR-T therapy in relapsed/refractory MCL after BTKi failure.

The British Society for Haematology provides updated, evidence-based guidelines on MCL diagnosis, risk stratification, and treatment algorithms, standardizing care for UK patients.

This review synthesizes MCL's genomic heterogeneity with the evolving therapeutic landscape, focusing on novel agents like BTKi and CAR-T and strategies for overcoming resistance in relapsed/refractory disease.

Pirtobrutinib, a non-covalent BTKi, shows a 52% overall response rate in relapsed/refractory MCL, including in patients previously treated with covalent BTKi, offering a new therapeutic option.