R-MACLO-IVAM regimen followed by maintenance therapy induces durable remissions in untreated mantle cell lymphoma - Long term follow up results

Juan P Alderuccio, Eduardo E Saul, Sunil G Iyer, Isildinha M Reis, Alvaro J Alencar, Joseph D Rosenblatt, Izidore S Lossos, Juan P Alderuccio, Eduardo E Saul, Sunil G Iyer, Isildinha M Reis, Alvaro J Alencar, Joseph D Rosenblatt, Izidore S Lossos

Abstract

We present long-term combined results of two clinical trials implementing R-MACLO-IVAM induction followed by thalidomide or rituximab maintenance in 44 patients with untreated mantle cell lymphoma (MCL). The first 22 patients (UM-MCL1 ClinicalTrials.gov identifier NCT00450801) received maintenance with thalidomide (200 mg daily until relapse/intolerable toxicity) and a subsequent cohort of 22 patients (UM-MCL2 ClinicalTrials.gov identifier NCT00878254) received rituximab (375 mg/m2 IV weekly × 4, repeated every 6 months for 3 years). Considering all 44 patients, 41 (93.2%) achieved complete response (CR), two (4.5%) partial response (PR), and one (2.3%) was not evaluated for response. With a median follow up of 7.2 years (range < 1 month to 16 years), the 5-year progression-free survival (PFS) was 55.6% (95% CI: 38.9%-69.4%) and median PFS 7.9 years (95% CI: 3.7-11 years). The 5-year OS was 83.3% (95% CI: 68.1%-91.7%) and median OS was not reached. Patients with blastic variant (n = 6) had a 5-year PFS and OS of 20.8% and 60%, respectively. Myelosuppression was the most common adverse event during immunochemotherapy. Long-term treatment-related mortality was 6.8%. Note, R-MACLO-IVAM followed by maintenance therapy is an effective regimen to induce long-term remission in MCL without need for consolidation with ASCT.

© 2021 Wiley Periodicals LLC.

References

REFERENCES

    1. Maddocks K. Update on mantle cell lymphoma. Blood. 2018;132:1647-1656.
    1. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th Rev ed. Lyon, France: IARC Press; 2017.
    1. Vose JM. Mantle cell lymphoma: 2017 update on diagnosis, risk-stratification, and clinical management. Am J Hematol. 2017;92:806-813.
    1. Martin P, Chadburn A, Christos P, et al. Intensive treatment strategies may not provide superior outcomes in mantle cell lymphoma: overall survival exceeding 7 years with standard therapies. Ann Oncol. 2008;19:1327-1330.
    1. Rule S. The modern approach to mantle cell lymphoma. Hematol Oncol. 2019;37(Suppl 1):66-69.
    1. Hermine O, Hoster E, Walewski J, et al. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL younger): a randomised, open-label, phase 3 trial of the European mantle cell lymphoma network. Lancet. 2016;388:565-575.
    1. Geisler CH, Kolstad A, Laurell A, et al. Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: still very long survival but late relapses do occur. Br J Haematol. 2012;158:355-362.
    1. Abrahamsson A, Albertsson-Lindblad A, Brown PN, et al. Real world data on primary treatment for mantle cell lymphoma: a Nordic lymphoma group observational study. Blood. 2014;124:1288-1295.
    1. LaCasce AS, Vandergrift JL, Rodriguez MA, et al. Comparative outcome of initial therapy for younger patients with mantle cell lymphoma: an analysis from the NCCN NHL database. Blood. 2012;119:2093-2099.
    1. Chihara D, Cheah CY, Westin JR, et al. Rituximab plus hyper-CVAD alternating with MTX/Ara-C in patients with newly diagnosed mantle cell lymphoma: 15-year follow-up of a phase II study from the MD Anderson Cancer Center. Br J Haematol. 2016;172(1):80-88.
    1. Romaguera JE, Fayad L, Rodriguez MA, et al. High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol. 2005;23:7013-7023.
    1. Bernstein SH, Epner E, Unger JM, et al. A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213. Ann Oncol. 2013;24:1587-1593.
    1. Merli F, Luminari S, Ilariucci F, et al. Rituximab plus HyperCVAD alternating with high dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma, a multicentre trial from Gruppo Italiano studio Linfomi. Br J Haematol. 2012;156:346-353.
    1. Geisler CH, Kolstad A, Laurell A, et al. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic lymphoma group. Blood. 2008;112:2687-2693.
    1. Le Gouill S, Thieblemont C, Oberic L, et al. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017;377:1250-1260.
    1. Kluin-Nelemans HC, Hoster E, Hermine O, et al. Treatment of older patients with mantle-cell lymphoma. N Engl J Med. 2012;367:520-531.
    1. Rummel MJ, Knauf W, Goerner M, et al. Two years rituximab maintenance vs. observation after first-line treatment with bendamustine plus rituximab (B-R) in patients with mantle cell lymphoma: first results of a prospective, randomized, multicenter phase II study (a subgroup study of the StiL NHL7-2008 MAINTAIN trial). J Clin Oncol. 2016;34(15_suppl):7503-7503.
    1. 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):1525-1525.
    1. Lossos IS, Hosein PJ, Morgensztern D, et al. High rate and prolonged duration of complete remissions induced by rituximab, methotrexate, doxorubicin, cyclophosphamide, vincristine, ifosfamide, etoposide, cytarabine, and thalidomide (R-MACLO-IVAM-T), a modification of the National Cancer Institute 89-C-41 regimen, in patients with newly diagnosed mantle cell lymphoma. Leuk Lymphoma. 2010;51:406-414.
    1. Hosein PJ, Sandoval-Sus JD, Goodman D, et al. Updated survival analysis of two sequential prospective trials of R-MACLO-IVAM followed by maintenance for newly diagnosed mantle cell lymphoma. Am J Hematol. 2015;90:E111-E116.
    1. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M. Report of the committee on Hodgkin's disease staging classification. Cancer Res. 1971;31:1860-1861.
    1. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059-3068.
    1. NCI. Common Terminology Criteria for Adverse Events (CTCAE) version 4. National Cancer Institute; 2010.
    1. Hoster E, Rosenwald A, Berger F, et al. Prognostic value of Ki-67 index, cytology, and growth pattern in mantle-cell lymphoma: results from randomized trials of the European mantle cell lymphoma network. J Clin Oncol. 2016;34:1386-1394.
    1. Hoster E, Dreyling M, Klapper W, et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood. 2008;111:558-565.
    1. Tamiflu and Aplastic anemia - a phase IV clinical study of FDA data. . Accessed February 26, 2021.
    1. Lossos C, Ferrell A, Duncan R, Lossos IS. Association between non-Hodgkin lymphoma and renal cell carcinoma. Leuk Lymphoma. 2011;52:2254-2261.
    1. Eskelund CW, Kolstad A, Jerkeman M, et al. 15-year follow-up of the second Nordic mantle cell lymphoma trial (MCL2): prolonged remissions without survival plateau. Br J Haematol. 2016;175:410-418.
    1. Fenske TS, Zhang MJ, Carreras J, et al. Autologous or reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chemotherapy-sensitive mantle-cell lymphoma: analysis of transplantation timing and modality. J Clin Oncol. 2014;32:273-281.
    1. Gerson JN, Handorf E, Villa D, et al. Survival outcomes of younger patients with mantle cell lymphoma treated in the rituximab era. J Clin Oncol. 2019;37:471-480.
    1. Metzner B, Muller TH, Gebauer W, et al. Long-term clinical and molecular remissions in patients with mantle cell lymphoma following high-dose therapy and autologous stem cell transplantation. Ann Hematol. 2014;93:803-810.
    1. Hoster E, Pott C. Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment. Hematology Am Soc Hematol Educ Program. 2016;2016:437-445.
    1. Kolstad A, Laurell A, Jerkeman M, et al. Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma. Blood. 2014;123:2953-2959.
    1. Pott C, Hoster E, Delfau-Larue MH, et al. Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study. Blood. 2010;115:3215-3223.
    1. Pott C, Hoster E, Beldjord K, et al. R-CHOP/R-DHAP compared to R-CHOP induction followed by high dose therapy with autologous stem cell transplantation induces higher rates of molecular remission in MCL: results of the MCL younger intergroup trial of the European MCL network. Blood. 2010;116:965-965.

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