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Expert Guidance for Mantle Cell Lymphoma

CME

Expert Guidance and Clinical Resources to Improve the Care of Patients With Mantle Cell Lymphoma

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Released: May 19, 2026

Expiration: November 18, 2026

Tycel J. Phillips
Tycel J. Phillips, MD
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References

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  24. Kumar A, Soumerai J, Abramson JS, et al. Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutation. Blood. 2025;145:497-507.
  25. Dreyling M, Doorduijn JK, Gine E, et al. Role of autologous stem cell transplantation in the context of ibrutinib-containing first-line treatment in younger patients with mantle cell lymphoma: results from the randomized triangle trial by the European MCL Network. Presented at: 66th Annual Meeting of the American Society of Hematology; December 7-10, 2024. Abstract 240.
  26. Bernard S, Goldwirt L, Amorim S, et al. Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse. Blood. 2015;126:1695-1698.
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  29. Wang M, Jurczak W, Trněný M, et al. Ibrutinib plus venetoclax in relapsed or refractory mantle cell lymphoma (SYMPATICO): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2025;26:200-213.
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  34. Cheah CY, George A, Giné E, et al. Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network. Ann Oncol. 2013;24:2119-2123.
  35. Ye H, Desai A, Zeng D, et al. Smoldering mantle cell lymphoma. J Exp Clin Cancer Res. 2017;36:185.
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  37. Tisi MC, Moia R, Patti C, et al. Long-term follow-up of rituximab plus bendamustine and cytarabine in older patients with newly diagnosed MCL. Blood Adv. 2023;7:3916-3924.
  38. Kumar A, Soumerai J, Karmali R, et al. Preliminary safety and efficacy of BOVen (zanubrutinib, obinutuzumab, and venetoclax) as frontline therapy for older patients with mantle cell lymphoma. Presented at: 67th Annual Meeting of the American Society of Hematology; December 6-9, 2025. Abstract 888.
  39. Jerkeman M, Wader K, Glimelius I, et al. Acalabrutinib and rituximab in elderly patients with newly diagnosed mantle cell lymphoma including a matched population-based external comparator- the Nordic Lymphoma Group NLG-MCL8 (ALTAMIRA) phase II trial. Presented at: 66th Annual Meeting of the American Society of Hematology; December 7-10, 2024. Abstract 747.
  40. Kumar A, Soumerai J, Abramson JS, et al. Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutation. Blood. 2025;145:497-507.
  41. Kim A, Riedell P, Ryan C, et al. Phase I/II study of acalabrutinib, venetoclax, and obinutuzumab in patients with relapsed/refractory and previously untreated mantle cell lymphoma (MAVO). Presented at: 67th Annual Meeting of the American Society of Hematology; December 6-9, 2025. Abstract 664.
  42. Lewis DJ, Jerkeman M, Sorrell L, et al. Ibrutinib-rituximab is superior to rituximab-chemotherapy in previously untreated older mantle cell lymphoma patients: results from the international randomised controlled trial, Enrich. Blood. 2024;144(suppl 1):235.
  43. Martin P, Cohen JB, Wang M, et al. Treatment outcomes and roles of transplantation and maintenance rituximab in patients with previously untreated mantle cell lymphoma: Results from large real-world cohorts. J Clin Oncol. 2023;41:541-554.
  44. Kansara R, Connors JM, Savage KJ, et al. Maintenance rituximab following induction R-CHOP chemotherapy in patients with composite or discordant, indolent and aggressive, B-cell non-Hodgkin lymphomas. Haematologica. 2016;101:e411-e414.
  45. Rummel MJ, Niederle N, Maschmeyer G, et al. 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. Lancet. 2013;381:1203-1210.
  46. Martin P, Cohen JB, Wang M, et al. Treatment outcomes and roles of transplantation and maintenance rituximab in patients with previously untreated mantle cell lymphoma: Results from large real-world cohorts. J Clin Oncol. 2023;41:541-554.
  47. Hill BT, Switchenko JM, Martin P, et al. Maintenance rituximab improves outcomes in mantle cell lymphoma patients who respond to induction therapy with bendamustine + rituximab without autologous transplant. Blood 2019;134(suppl 1):1525.
  48. Wang Y, Larson MC, Kumar A, et al. Benefit of rituximab maintenance after first-line bendamustine-rituximab in mantle cell lymphoma. J Clin Oncol. 2024;42(16 suppl):7006.
  49. Ladetto M, Gutmair K, Doorduijn JK, et al. Impact of rituximab maintenance added to ibrutinib-containing regimens with and without ASCT in younger, previously untreated MCL patients: an analysis of the triangle data embedded in the multiply project. Presented at: 66th Annual Meeting of the American Society of Hematology; December 7-10, 2024. Abstract 237.
  50. Sarkozy C, Thieblemont C, Oberic L, et al. Long-term follow-up of rituximab maintenance in young patients with mantle-cell lymphoma included in the LYMA trial: A LYSA Study. J Clin Oncol. 2024;42:769-773.
  51. Fowler NH. Role of maintenance rituximab (Rituxan) therapy in the treatment of follicular lymphoma. P T. 2011;36:590-598.
  52. Sarkozy C, Callanan M, Thieblemont C, et al. Obinutuzumab vs rituximab for transplant-eligible patients with mantle cell lymphoma. Blood. 2024;144:262-271.
  53. Young RM, Staudt LM. Targeting pathological B cell receptor signalling in lymphoid malignancies. Nat Rev Drug Discov. 2013;12:229-243.
  54. Wang ML, Jurczak W, Jerkeman M, et al. Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma. N Engl J Med. 2022;386:2482-2494.
  55. Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369:507-516.
  56. Peterson D, Schwartz J. Ibrutinib in relapsed or refractory mantle cell lymphoma and chronic lymphocytic leukemia. J Adv Pract Oncol. 2014;5:348-354.
  57. Ibrutinib [prescribing information]. South San Francisco, CA: Pharmacyclics LLC; 2024.
  58. Dreyling M, Doorduijn J, Giné E, et al. Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network. Lancet. 2024;403:2293-2306.
  59. Seymour JF, Byrd JC, Ghia P, et al. Detailed safety profile of acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia in the ELEVATE-RR trial. Blood. 2023;142:687-699.
  60. Brown JR, Eichhorst BF, Lamanna N, et al. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE. Blood. 2024;144:2706-2717.
  61. Dimopoulos MA, Opat S, D’Sa S, et al. Zanubrutinib versus ibrutinib in symptomatic Waldenström macroglobulinemia: final analysis from the randomized phase III ASPEN study. J Clin Oncol. 2023;41:5099-5106.
  62. O’Brien SM, Brown JR, Byrd JC, et al. Monitoring and managing BTK inhibitor treatment-related adverse events in clinical practice. Front Oncol. 2021;11:720704.
  63. Wang ML, Cohen J, Shah N, et al. Pirtobrutinib in relapsed/refractory (R/R) mantle cell lymphoma (MCL): final update from the phase 1/2 BRUIN study. Presented at: 67th Annual Meeting of the American Society of Hematology; December 6-9, 2025. Abstract 7068.
  64. Zanubrutinib [prescribing information]. San Mateo, CA: BeiGene USA, Inc; 2025.
  65. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study. Presented at: 62nd Annual Meeting of the American Society of Hematology; December 5-8, 2020. Abstract 2040.
  66. Wang ML, Paludo J, Farias JSH, et al. Time to third-line treatment after bendamustine-rituximab with or without acalabrutinib in patients with previously untreated mantle cell lymphoma: updated analysis of the phase 3 ECHO trial after 50 months of follow-up. Presented at: 67th Annual Meeting of the American Society of Hematology; December 6-9, 2025. Abstract 885.
  67. Wagner-Johnston N, Jegede O, Spurgeon SE, et al. Addition or substitution of acalabrutinib in intensive frontline chemoimmunotherapy for patients ≤70 years old with mantle cell lymphoma: outcomes of the 3-arm randomized phase II intergroup trial ECOG-ACRIN EA4181. Presented at: 66th Annual Meeting of the American Society of Hematology; December 7-10, 2024. Abstract 236.
  68. Hawkes E, Romejko-Jarosinska J, Jurczak W, et al. Acalabrutinib plus venetoclax and rituximab in patients with treatment-naive (TN) mantle cell lymphoma (MCL): results from the phase 2 TrAVeRse study. Presented at: 67th Annual Meeting of the American Society of Hematology; December 6-9, 2025. Abstract 884.
  69. Song Y, Zhou K, Zou D, et al. Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study. Blood. 2022;139:3148-3158.
  70. Eskelund CW, Dahl C, Hansen JW, et al. TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy. Blood. 2017;130:1903-1910.
  71. Malinverni C, Bernardelli A, Glimelius I, et al. Outcomes of younger patients with mantle cell lymphoma experiencing late relapse (>24 months): the LATE-POD study. Blood. 2024;144:1001-1009.
  72. Song Y, Zhou K, Zou D, et al. Long-term outcomes of second-line vs later-line zanubrutinib treatment in patients with relapsed/refractory MCL: an updated pooled analysis. Presented at the 64th Annual Meeting of the American Society of Hematology; December 10-13, 2022. Abstract 2894.
  73. Wang M, Jurczak W, Trneny M, et al. Efficacy and safety of ibrutinib plus venetoclax in patients with mantle cell lymphoma (MCL) and TP53 mutations in the SYMPATICO study. Presented at: Annual Meeting of the American Society of Clinical Oncology; May 31-June 4, 2024. Abstract 7007.
  74. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study. Blood. 2020;136:38-39.
  75. Nakhoda S, Vistarop A, Wang YL. Resistance to Bruton tyrosine kinase inhibition in chronic lymphocytic leukaemia and non-Hodgkin lymphoma. Br J Haematol. 2023;200:137-149.
  76. Ondrisova L, Mraz M. Genetic and non-genetic mechanisms of resistance to BCR signaling inhibitors in B cell malignancies. Front Oncol. 2020;10:591577.
  77. Hershkovitz-Rokah O, Pulver D, Lenz G, et al. Ibrutinib resistance in mantle cell lymphoma: clinical, molecular and treatment aspects. Br J Haematol. 2018;181:306-319.
  78. Cheah CY, Chihara D, Romaguera JE, et al. Patients with mantle cell lymphoma failing ibrutinib are unlikely to respond to salvage chemotherapy and have poor outcomes. Ann Oncol. 2015;26:1175-1179.
  79. Martin P, Maddocks K, Leonard JP, et al. Postibrutinib outcomes in patients with mantle cell lymphoma. Blood. 2016;127:1559-1563.
  80. Dreyling M, Jurczak W, Jerkeman M, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016;387:770-778.
  81. Epperla N, Hamadani M, Cashen AF, et al. Predictive factors and outcomes for ibrutinib therapy in relapsed/refractory mantle cell lymphoma—a “real world” study. Hematol Oncol. 2017;35:528-535.
  82. Byrd JC, Owen R, O’Brien SM, et al. Pooled analysis of safety data from clinical trials evaluating acalabrutinib monotherapy in hematologic malignancies. Blood. 2017;130(suppl 1):4326.
  83. Tam CS, Opat S, D’Sa S, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood. 2020;136:2038-2050.
  84. Wang M, Munoz J, Goy A, et al. Three-year follow-up of KTE-X19 in patients with relapsed/refractory mantle cell lymphoma, including high-risk subgroups, in the ZUMA-2 Study. J Clin Oncol. 2023;41:555-567.
  85. Muñoz J, Locke FL, Reagan PM, et al. Five-year follow-up of patients with relapsed/refractory mantle cell lymphoma treated with anti-CD19 CAR T-cell therapy in ZUMA-2, cohorts 1 and 2. J Hematol Oncol. 2026 Apr 27.
  86. Wang Y, Jain P, Locke FL, et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023;41:2594-2606.
  87. Neelapu SS, Jacobson CA, Ghobadi A, et al. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2023;141:2307-2315.
  88. van Meerten T, Kersten MJ, Iacoboni G, et al. Brexucabtagene autoleucel for BTKi-naive relapsed/refractory mantle cell lymphoma: primary analysis of ZUMA-2 cohort 3. Blood. 2025;147:1302-1314.
  89. Wang M, Siddiqi T, Gordon LI, et al. Lisocabtagene maraleucel in relapsed/refractory mantle cell lymphoma: Primary analysis of the mantle cell lymphoma cohort from TRANSCEND NHL 001, a phase I multicenter seamless design study. J Clin Oncol. 2024;42:1146-1157.
  90. Brexucabtagene autoleucel [prescribing information]. Santa Monica, CA: Kite Pharma, Inc; 2024
  91. Lisocabtagene maraleucel [prescribing information]. Bothell, WA: Juno Therapeutics Inc, a Bristol-Myers Squibb Company; 2024.
  92. Lewis KL, Cheah CY. Non-covalent BTK inhibitors—the new BTKids on the block for B-cell malignancies. J Pers Med. 2021;11:764.
  93. Pirtobrutinib [prescribing information]. Indianapolis, IN: Lilly USA, LLC; 2023.
  94. Shah NN, Wang M, Roeker LE, et al. Pirtobrutinib monotherapy in Bruton tyrosine kinase inhibitor-intolerant patients with B-cell malignancies: results of the phase I/II BRUIN trial. Haematologica. 2025;110:92-102.
  95. Wang M, Eyre TA, Shah NN, et al. BRUIN MCL-321: a phase 3, open-label, randomized study of pirtobrutinib versus investigator choice of BTK inhibitor in patients with previously treated, BTK inhibitor naïve mantle cell lymphoma. Presented at: Annual Meeting of the American Society of Clinical Oncology; June 2-6, 2023. Abstract TPS7587.
  96. Eyre TA, Shah NN, Dreyling M, et al. BRUIN MCL-321: phase III study of pirtobrutinib versus investigator choice of BTK inhibitor in BTK inhibitor naive mantle cell lymphoma. Future Oncol. 2022;18:3961-3969.
  97. US Food and Drug Administration. FDA grants accelerated approval to sonrotoclax for relapsed or refractory mantle cell lymphoma. fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sonrotoclax-relapsed-or-refractory-mantle-cell-lymphoma. Accessed May 18, 2026.
  98. Liu J, Li S, Wang Q, et al. Sonrotoclax overcomes BCL2 G101V mutation–induced venetoclax resistance in preclinical models of hematologic malignancy. Blood 2024;143:1825.
  99. Wang M, Song Y, Hermine O, et al. Sonrotoclax (BGB-11417) monotherapy in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) previously treated with a Bruton tyrosine kinase (BTK) inhibitor: early results from a phase 1/2 study. Presented at: 67th Annual Meeting of the American Society of Hematology; December 6-9, 2025. Abstract 663.
  100. Phillips TJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab in relapsed/refractory mantle cell lymphoma: results from a phase I/II study. J Clin Oncol. 2025;43:318-328.
  101. Budde LE, Kamdar M, Assouline SE, et al. Mosunetuzumab plus polatuzumab vedotin in relapsed/refractory MCL after BTK inhibitor therapy: a phase 2 study. Blood. 2026;[Epub ahead of print].

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