MCL Literature Feed

This review summarizes the shift towards frontline BTK inhibitor-based regimens, including chemotherapy-free options and combinations for high-risk MCL, potentially replacing autologous stem cell transplant consolidation.

A matching-adjusted indirect comparison suggests pirtobrutinib improves survival versus standard of care for relapsed/refractory MCL patients who have progressed on a prior covalent BTKi, supporting its use.

The phase 3 TRIANGLE trial shows adding ibrutinib to frontline chemoimmunotherapy and autologous transplant improves failure-free survival, establishing a new standard of care for young, fit MCL patients.

This preclinical study shows a SOX11 inhibitor overcomes BTKi, BCL2i, and CAR-T resistance by targeting the PAX5/CD19 axis, a novel upstream BCR signaling mechanism.

This case report links the next-generation BTKi orelabrutinib to multiple skin cancers, suggesting this toxicity may be a class effect and reinforcing the need for dermatologic surveillance.

This review summarizes the MCL treatment evolution from chemoimmunotherapy and transplant to targeted agents (BTKi) and immunotherapies (CAR-T, bispecifics), emphasizing a future of personalized, genomics-guided care.

Acquired MYC rearrangements were found in 43% of ibrutinib-resistant MCL tumors, identifying a key genomic alteration that drives intrinsic resistance and may serve as a critical biomarker.

Real-world data from older Chinese MCL patients shows BTKi-based regimens and maintenance therapy significantly improve survival, validating these strategies for this specific, understudied elderly population.

This indirect treatment comparison provides the first comparative evidence between zanubrutinib and acalabrutinib for relapsed/refractory MCL, guiding clinical selection in the absence of a head-to-head trial.

This review summarizes the evolution of BTK inhibitors, from covalent to reversible agents, to overcome resistance and toxicity, highlighting their central role in current and future MCL therapies.

This review summarizes preclinical nanocarrier strategies designed to improve ibrutinib's bioavailability and targeted delivery, potentially enhancing efficacy and reducing off-target toxicity for MCL patients in the future.

In the BRUIN study, relapsed/refractory MCL patients previously treated with a BTKi maintained or improved quality of life and symptoms on pirtobrutinib, supporting its favorable long-term tolerability.

Pirtobrutinib-tolerant MCL persister cells survive via a reversible TCA cycle metabolic switch, presenting a novel metabolic vulnerability to target and prevent drug resistance.

Blastoid or pleomorphic morphology in mantle cell lymphoma is associated with increased primary and acquired resistance to BTK inhibitors, identifying a high-risk population requiring alternative therapeutic strategies.

This review explains how tumor microenvironment crosstalk with B-cell receptor signaling promotes MCL survival and BTKi resistance, underscoring the need to target these interactions for improved therapies.

Long-term follow-up (37.2 months) in Japanese relapsed/refractory MCL patients shows the ibrutinib-venetoclax combination yields durable complete responses (83% CR), high MRD negativity, and a manageable safety profile.

The Japanese PMDA has approved the BTK inhibitor acalabrutinib for treating mantle cell lymphoma, providing a new therapeutic option for patients in Japan.

This review advocates for integrating BTK inhibitors into frontline MCL therapy for all patients, particularly for TP53-mutated disease, challenging the standard role of chemotherapy.

Frontline ibrutinib-rituximab improves progression-free survival over immunochemotherapy in older MCL patients, establishing a new chemotherapy-free standard of care option.

This review provides a framework for selecting frontline therapies for older MCL patients, weighing less-intensive chemoimmunotherapy against novel agents like BTK inhibitors based on patient-specific factors.

This SHINE trial analysis shows ibrutinib's PFS benefit with BR is consistent across exposure levels, supporting dose reductions for toxicities like atrial fibrillation without compromising efficacy.

In a US community setting, real-world data shows MCL patients on zanubrutinib had significantly longer treatment duration and adherence compared to acalabrutinib and ibrutinib, suggesting better persistence.

A 2022 real-world Japanese study shows chemotherapy remains dominant frontline while BTKis are common second-line, with physicians prioritizing quality of life for BTKi-treated patients over tumor response.

NCCN guidelines now highlight BTK inhibitor-based regimens as effective options for high-risk, TP53-mutated classical mantle cell lymphoma, formalizing a key strategy for this difficult-to-treat population.

Acalabrutinib plus rituximab successfully resolved paraneoplastic glomerulonephritis in an MCL patient, offering a new treatment approach for this rare renal complication.

All BTK inhibitors impair platelet aggregation in MCL as a class effect, regardless of BTK specificity or dose, providing a clear mechanism for the bleeding risk seen with these agents.

Preclinical research shows ibrutinib inhibits poxvirus replication by targeting BTK, suggesting a potential secondary antiviral benefit for immunocompromised MCL patients receiving this therapy.

Ibrutinib can cause rare but severe hepatic subcapsular hematomas in relapsed MCL; ultrasound is a key tool for early diagnosis and monitoring of this bleeding complication.

BRG1-driven suppression of ferroptosis is a key mechanism of BTKi resistance in MCL, and pharmacologic BRG1 inhibition restores BTKi sensitivity, suggesting a new combination therapy.

This review argues that new agents like BTKi are disrupting the frontline MCL standard of care, challenging ASCT's role and demanding personalized, risk-adapted treatment guidelines to resolve clinical uncertainty.