Medscape InDiscussion: Mantle Cell Lymphoma Medscape

Drs Peter Martin and Anita Kumar discuss covalent and noncovalent Bruton tyrosine kinase (BTK) inhibitors in the frontline setting, BTK mutations, and the complicated mechanisms of resistance.
Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/982893). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals.
Resources
Long-term Follow-up of MCL Patients Treated With Single-Agent Ibrutinib: Updated Safety and Efficacy Results https://pubmed.ncbi.nlm.nih.gov/26059948/
Acalabrutinib in Relapsed or Refractory Mantle Cell Lymphoma (ACE-LY-004): A Single-Arm, Multicentre, Phase 2 Trial https://pubmed.ncbi.nlm.nih.gov/29241979/
Treatment of Patients With Relapsed or Refractory Mantle-Cell Lymphoma With Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase https://pubmed.ncbi.nlm.nih.gov/32461234/
Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects https://pubmed.ncbi.nlm.nih.gov/33777941/
The Potential of Pirtobrutinib in Multiple B-cell Malignancies https://pubmed.ncbi.nlm.nih.gov/35747462/
Pirtobrutinib in Relapsed or Refractory B-cell Malignancies (BRUIN): A Phase 1/2 Study https://pubmed.ncbi.nlm.nih.gov/33676628/
Postibrutinib Outcomes in Patients With Mantle Cell Lymphoma https://pubmed.ncbi.nlm.nih.gov/26764355/
Genetic Heterogeneity in Primary and Relapsed Mantle Cell Lymphomas: Impact of Recurrent CARD11 Mutations https://pubmed.ncbi.nlm.nih.gov/27224912/
NF-κB Signaling and Its Relevance to the Treatment of Mantle Cell Lymphoma https://pubmed.ncbi.nlm.nih.gov/29907126/
Mechanisms of Resistance to Noncovalent Bruton's Tyrosine Kinase Inhibitors https://pubmed.ncbi.nlm.nih.gov/35196427/
Ibrutinib Plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma https://pubmed.ncbi.nlm.nih.gov/35657079/
Efficacy and Safety of Ibrutinib Combined With Standard First-line Treatment or as Substitute for Autologous Stem Cell Transplantation in Younger Patients With Mantle Cell Lymphoma: Results From the Randomized Triangle Trial by the European MCL Network https://ashpublications.org/blood/article/140/Supplement%201/1/490022/Efficacy-and-Safety-of-Ibrutinib-Combined-with
Zanubrutinib, Obinutuzumab, and Venetoclax With Minimal Residual Disease-Driven Discontinuation in Previously Untreated Patients With Chronic Lymphocytic Leukaemia or Small Lymphocytic Lymphoma: A Multicentre, Single-arm, Phase 2 Trial https://pubmed.ncbi.nlm.nih.gov/34826411/
A Phase II Study of Zanubrutinib, Obinutuzumab, and Venetoclax in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia https://www.mskcc.org/cancer-care/clinical-trials/18-427
Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma https://clinicaltrials.gov/ct2/show/NCT03223610
Phase 2 Trial of Acalabrutinib-Lenalidomide-Rituximab (ALR) With Real-time Monitoring of MRD in Patients With Treatment-Naïve Mantle Cell Lymphoma https://ashpublications.org/blood/article/140/Supplement%201/175/489040/Phase-2-Trial-of-Acalabrutinib-Lenalidomide
A Phase III Study of Zanubrutinib Plus Rituximab Versus Bendamustine Plus Rituximab in Transplant-Ineligible, Untreated Mantle Cell Lymphoma https://pubmed.ncbi.nlm.nih.gov/32985902/
A Study Looking at Ibrutinib for Older People With Mantle Cell Lymphoma (ENRICH) https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-ibrutinib-for-older-people-with-mantle-cell-lymphoma-enrich
Treatment Outcomes and Roles of Transplantation and Maintenance Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma: Results From Large Real-World Cohorts https://pubmed.ncbi.nlm.nih.gov/35763708/

Drs Peter Martin and Eric Hsi have a thought-provoking discussion on key topics in the pathology of mantle cell lymphoma, including biopsies, diagnostic markers, and what the future holds for treatment.
Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/982892). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals.
Resources
College of American Pathologists https://www.cap.org
American Society of Clinical Pathology https://www.ascp.org/content
American Society of Hematology https://www.hematology.org/
Alliance for Clinical Trials in Oncology https://www.allianceforclinicaltrialsinoncology.org/main/
Diagnostic Accuracy of SOX11 Immunohistochemistry in Mantle Cell Lymphoma: A Meta-analysis https://pubmed.ncbi.nlm.nih.gov/31714947/
SOX11 Expression Is Highly Specific for Mantle Cell Lymphoma and Identifies the Cyclin D1-Negative Subtype https://pubmed.ncbi.nlm.nih.gov/19880778/
Prognostic Role of SOX11 in a Population-Based Cohort of Mantle Cell Lymphoma https://pubmed.ncbi.nlm.nih.gov/22431568/
Genomic and Epigenomic Insights Into the Origin, Pathogenesis, and Clinical Behavior of Mantle Cell Lymphoma Subtypes https://pubmed.ncbi.nlm.nih.gov/32584970/
Gastrointestinal Involvement in Patients With Mantle Cell Lymphoma: A Single Center Experience of Eighty-Five Patients https://pubmed.ncbi.nlm.nih.gov/30677768/
Incidence of Preclinical Manifestations of Mantle Cell Lymphoma and Mantle Cell Lymphoma In Situ in Reactive Lymphoid Tissues https://pubmed.ncbi.nlm.nih.gov/22790016/
PacBio https://www.pacb.com/
Cell Cycle Dysregulation in Mantle Cell Lymphoma: Genomics and Therapy https://pubmed.ncbi.nlm.nih.gov/32861279/
Ki67 and PIM1 Expression Predict Outcome in Mantle Cell Lymphoma Treated With High Dose Therapy, Stem Cell Transplantation and Rituximab: A Cancer and Leukemia Group B 59909 Correlative Science Study https://pubmed.ncbi.nlm.nih.gov/19021050/

Drs Peter Martin and Michael Wang discuss the role of CAR T cells in mantle cell lymphoma, how they are used with respect to bridging therapy, and the surveillance and management of toxicities.
Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/982891). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals.
Resources
Mantle Cell Lymphoma https://emedicine.medscape.com/article/203085-overview
KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma https://pubmed.ncbi.nlm.nih.gov/32242358/
Three-Year Follow-up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study https://pubmed.ncbi.nlm.nih.gov/35658525/
Brexucabtagene Autoleucel for Relapsed/Refractory Mantle Cell Lymphoma: Real World Experience From the US Lymphoma CAR T Consortium https://ashpublications.org/blood/article/138/Supplement%201/744/479986/Brexucabtagene-Autoleucel-for-Relapsed-Refractory
Real-World Evidence of Brexucabtagene Autoleucel for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma https://pubmed.ncbi.nlm.nih.gov/35271707/
Frequency of Gastrointestinal Involvement and Its Clinical Significance in Mantle Cell Lymphoma https://pubmed.ncbi.nlm.nih.gov/12548600/
Society for Immunotherapy of Cancer (SITC) Clinical Practice Guideline on Immune Effector Cell-Related Adverse Events https://pubmed.ncbi.nlm.nih.gov/33335028/
Management of a Patient With Mantle Cell Lymphoma Who Developed Severe Neurotoxicity After Chimeric Antigen Receptor T-cell Therapy in ZUMA-2 https://pubmed.ncbi.nlm.nih.gov/33067318/
Experiences With Glofitamab Administration Following CAR T Therapy in Patients With Relapsed Mantle Cell Lymphoma https://pubmed.ncbi.nlm.nih.gov/36078155/
Glofitamab Monotherapy Induces High Complete Response Rates in Patients With Heavily Pretreated Relapsed or Refractory Mantle Cell Lymphoma https://ash.confex.com/ash/2022/webprogram/Paper157777.html
GEN3013, Epcoritamab Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma EPCORE™ NHL-1 https://www.clinicaltrials.gov/ct2/show/NCT03625037

Drs Peter Martin and Kami Maddocks discuss bendamustine, its effectiveness in older patients, and the challenge of combining treatments or other medications with that backbone.
Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/982890). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals.
Resources
Mantle Cell Lymphoma https://emedicine.medscape.com/article/203085-overview
Bendamustine https://reference.medscape.com/drug/bendeka-belrapzo-bendamustine-342133
Bendamustine Plus Rituximab Versus CHOP Plus Rituximab as First-Line Treatment for Patients With Indolent and Mantle-Cell Lymphomas: An Open-Label, Multicentre, Randomised, Phase 3 Non-Inferiority Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61763-2/fulltext
Randomized Trial of Bendamustine-Rituximab or R-CHOP/R-CVP in First-Line Treatment of Indolent NHL or MCL: The BRIGHT Study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/
ECOG-ACRIN E1411 Randomized Phase 2 Trial of Bendamustine-Rituximab (BR)-Based Induction Followed by Rituximab (R) ± Lenalidomide (L) Consolidation for Mantle Cell Lymphoma: Effect of Adding Bortezomib to Front-Line BR Induction on PFS. https://ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.7503
A Phase 1/1b Study of Rituximab, Bendamustine, and Ibrutinib in Patients With Untreated and Relapsed/Refractory Non-Hodgkin Lymphoma https://ashpublications.org/blood/article/125/2/242/34217/A-phase-1-1b-study-of-rituximab-bendamustine-and
Ibrutinib Plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma https://pubmed.ncbi.nlm.nih.gov/35657079/
Five-Year Outcomes of the S1106 Study of R-Hyper-CVAD vs R-Bendamustine in Transplant-Eligible Patients With Mantle Cell Lymphoma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849956/
A Randomized 3-Arm Phase II Study Comparing 1.) Bendamustine, Rituximab, and High Dose Cytarabine (BR/CR) 2.) Bendamustine, Rituximab, High Dose Cytarabine and Acalabrutinib (BR/CR-A), and 3.) Bendamustine, Rituximab and Acalabrutinib (BR-A) in Patients ≤ 70 Years Old With Untreated Mantle Cell Lymphoma https://ecog-acrin.org/clinical-trials/ea4181-educational-materials/
Rituximab With or Without Stem Cell Transplant in Treating Patients With Minimal Residual Disease-Negative Mantle Cell Lymphoma in First Complete Remission https://ecog-acrin.org/clinical-trials/ea4151-mantle-cell-lymphoma/
Treatment Outcomes and Roles of Transplantation and Maintenance Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma: Results From Large Real-World Cohorts https://pubmed.ncbi.nlm.nih.gov/35763708/
Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study https://pubmed.ncbi.nlm.nih.gov/35658525/
Efficacy and Safety of Ibrutinib Combined With Standard First-Line Treatment or As Substitute for Autologous Stem Cell Transplantation in Younger Patients With Mantle Cell Lymphoma: Results From the Randomized Triangle Trial by the European MCL Network https://ash.confex.com/ash/2022/webprogram/Paper163018.html

Drs Peter Martin and Eva Hoster discuss minimal residual disease, the Mantle Cell Lymphoma International Prognostic Index, and newer variable additions and their role in understanding recent findings.
Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/982889). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals.
Resources
Predictive Value of Minimal Residual Disease on Efficacy of Rituximab Maintenance in Mantle Cell Lymphoma: Results From the European MCL Elderly Trial https://ashpublications.org/blood/article/140/Supplement%201/1304/491631/Predictive-Value-of-Minimal-Residual-Disease-on
Mantle Cell Lymphoma https://emedicine.medscape.com/article/203085-overview
A New Prognostic Index (MIPI) for Patients With Advanced-Stage Mantle Cell Lymphoma https://pubmed.ncbi.nlm.nih.gov/17962512/
German Lymphoma Alliance Scores https://www.german-lymphoma-alliance.de/Scores.html
Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-term Follow-up of the Randomized European MCL Elderly Trial https://pubmed.ncbi.nlm.nih.gov/31804876/
Rituximab-Lenalidomide (R2) Maintenance Is Superior to Rituximab Maintenance After First-line Immunochemotherapy in Mantle Cell Lymphoma: Results of the MCL R2 Elderly Clinical Trial https://ashpublications.org/blood/article/138/Supplement%201/379/478205/Rituximab-Lenalidomide-R2-Maintenance-Is-Superior
ASCT After a Rituximab/Ibrutinib/Ara-c Containing iNduction in Generalized Mantle Cell Lymphoma https://clinicaltrials.gov/ct2/show/NCT02858258

Drs Peter Martin and Brad Kahl discuss autologous stem cell transplantation for mantle cell lymphoma, the TRIANGLE trial results, and the transition toward use of Bruton tyrosine kinase inhibitors.
Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/982888). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals.
Resources
Long Term Follow up of the Resort Study (E4402): A Randomized Phase III Study Comparing Two Different Rituximab Dosing Strategies for Low Tumor Burden Follicular Lymphoma https://ashpublications.org/blood/article/138/Supplement%201/815/480037/Long-Term-Follow-up-of-the-Resort-Study-E4402-A
Phase 2 Study of VcR-CVAD With Maintenance Rituximab for Untreated Mantle Cell Lymphoma: An Eastern Cooperative Oncology Group Study (E1405) https://pubmed.ncbi.nlm.nih.gov/24458437/
High-Dose Cytarabine and Autologous Stem-Cell Transplantation in Mantle Cell Lymphoma: Long-Term Follow-Up of the Randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network https://ascopubs.org/doi/abs/10.1200/JCO.22.01780
Ten-Year Follow-up After Intense Chemoimmunotherapy With Rituximab-HyperCVAD Alternating With Rituximab-High Dose Methotrexate/Cytarabine (R-MA) and Without Stem Cell Transplantation in Patients With Untreated Aggressive Mantle Cell Lymphoma https://pubmed.ncbi.nlm.nih.gov/20528872/
Mantle Cell Lymphoma https://emedicine.medscape.com/article/203085-overview
Primary Results From the Double-Blind, Placebo-Controlled, Phase III SHINE Study of Ibrutinib in Combination With Bendamustine-Rituximab (BR) and R Maintenance as a First-Line Treatment for Older Patients With Mantle Cell Lymphoma (MCL). https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.17_suppl.LBA7502
Efficacy and Safety of Ibrutinib Combined With Standard First-Line Treatment or as Substitute for Autologous Stem Cell Transplantation in Younger Patients With Mantle Cell Lymphoma: Results From the Randomized Triangle Trial by the European MCL Network https://ashpublications.org/blood/article/140/Supplement%201/1/490022/Efficacy-and-Safety-of-Ibrutinib-Combined-with
Bendamustine and Rituximab Alternating With Cytarabine and Rituximab for Untreated Mantle Cell Lymphoma https://clinicaltrials.gov/ct2/show/NCT02728531
Rituximab With or Without Stem Cell Transplant in Treating Patients With Minimal Residual Disease-Negative Mantle Cell Lymphoma in First Complete Remission https://clinicaltrials.gov/ct2/show/NCT03267433