MCL Literature Feed

This review summarizes the integration of BTK inhibitors into frontline MCL therapy and the emerging role of MRD, providing a treatment algorithm for managing newly diagnosed patients.

In elderly, frontline MCL, this SHINE secondary analysis shows achieving a complete response is critical for long-term PFS, and adding ibrutinib to BR significantly increases CR rates.

This phase II trial protocol compares chemo-free ibrutinib/venetoclax/rituximab versus ibrutinib-chemoimmunotherapy in treatment-naive elderly MCL, aiming to establish a new frontline standard.

This case series reports fatal Hepatitis B reactivation with ibrutinib and breakthrough reactivation on zanubrutinib despite prophylaxis, highlighting the need for vigilant HBV monitoring with all BTKis.

A preclinical mouse study reveals acalabrutinib alleviates fatty liver disease by regulating bile acid metabolism, suggesting a novel, off-target effect potentially beneficial for MCL patients with this comorbidity.

Genomic analysis of MCL treated sequentially with BTKi and venetoclax identifies specific copy number alterations (e.g., 9p21.3 deletion) as novel biomarkers for primary and acquired resistance.

This Danish population-based study shows real-world ibrutinib outcomes (PFS 5.8 months) are inferior to clinical trials, with high-risk features and toxicity limiting efficacy, underscoring significant unmet needs.

In untreated mantle cell lymphoma, adding acalabrutinib to bendamustine-rituximab significantly improves progression-free survival with manageable toxicity, offering a potentially safer chemoimmunotherapy combination than ibrutinib-based regimens.

This review summarizes recent phase II/III trial data supporting the integration of covalent BTK inhibitors into frontline MCL therapy, proposing new treatment algorithms for this setting.

A four-decade analysis demonstrates significant, gradual overall survival improvement in MCL, validating the cumulative clinical impact of evolving therapies from chemotherapy to novel agents and transplant.

M2-polarized macrophages drive ibrutinib resistance via the CXCL5/CXCR2 axis; a CXCR2 inhibitor re-sensitizes MCL cells, suggesting a novel combination therapy to overcome BTKi resistance.

This review of FDA-approved covalent inhibitors highlights the foundational role of BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) in MCL, which established this successful drug development strategy.

Real-world data on the ibrutinib, lenalidomide, and rituximab triplet in relapsed/refractory non-Hodgkin lymphoma provides practical insights into the efficacy and safety of this chemotherapy-free regimen.

This MZL case identifies BTK C481S and PLCG2 D334H co-mutations driving zanubrutinib resistance, a mechanism highly relevant to BTKi failure and subsequent treatment strategies in relapsed MCL.

This study identifies predictors of outcome for covalent BTKi therapy in relapsed/refractory TP53-mutant MCL, helping to risk-stratify patients and guide subsequent treatment decisions.

The MCL35 gene expression assay identifies high-risk older patients who do not benefit from adding ibrutinib to bendamustine-rituximab, mandating alternative frontline strategies for this molecularly-defined subgroup.

The combination of ibrutinib and venetoclax improves progression-free survival in relapsed/refractory MCL, establishing a highly effective, chemotherapy-free regimen for this difficult-to-treat population.

This preclinical study demonstrates potent anti-MCL activity with a triple combination of bendamustine, acalabrutinib, and venetoclax, providing a strong rationale for future clinical trials.

This large real-world analysis of elderly MCL patients shows improved first-line survival with modern therapies, but only modest survival gains after relapse, highlighting a critical unmet clinical need.

In Chinese patients with relapsed/refractory MCL previously treated with a covalent BTKi, the non-covalent BTKi pirtobrutinib achieved a 62.9% overall response rate, confirming its global efficacy.

This review outlines the evolving MCL treatment paradigm, emphasizing earlier BTKi use, established CAR-T, and emerging non-covalent BTKi and bispecifics for high-risk disease like TP53-mutated MCL.

An updated indirect comparison suggests zanubrutinib provides significantly longer progression-free survival than orelabrutinib in relapsed/refractory MCL, informing BTKi choice in the absence of head-to-head trial data.

This case series reports uveal melanoma development in patients on BTK inhibitors, suggesting a potential rare but serious toxicity and warranting increased ophthalmologic surveillance for this common MCL therapy.

This review advocates for adding a BTKi to frontline immunochemotherapy for transplant-eligible patients as a new standard of care, while also summarizing its emerging role in older patients.

This preclinical study identifies CEACAM1 as a novel activator of B-cell receptor signaling by recruiting SYK, revealing a new potential therapeutic target and mechanism of resistance to BCR inhibitors.

Overexpression of IL-16 drives BTKi resistance via the CD9/NF-κB/AKT axis in MCL models, presenting a novel therapeutic target to overcome treatment failure and restore drug sensitivity.

This review summarizes favorable outcomes for CAR-T and bispecific antibodies in relapsed/refractory MCL, detailing their integration into the treatment paradigm for patients with poor prognoses post-BTKi.

This phase 2 trial shows ibrutinib is effective in high-risk, previously untreated smoldering MCL, suggesting early intervention with a BTKi can delay progression in this traditionally observed population.

This review synthesizes mechanisms of BTKi resistance and highlights next-generation strategies like noncovalent BTKi and PROTACs to overcome this critical challenge in relapsed/refractory MCL.

A novel high-performance liquid chromatography-ultraviolet (HPLC-UV) assay was developed to measure pirtobrutinib levels, enabling therapeutic drug monitoring to potentially optimize dosing in MCL patients.