Treatment of patients with MYC rearrangement positive large B-cell lymphoma with R-CHOP plus phaselenalidomide: II HOVON trial results of a multicenter

Martine E.D. Chamuleau*, Coreline N. Burggraaff, Marcel Nijland, Katerina Bakunina, Rogier Mous, Pieternella J. Lugtenburg, Daan Dierickx, Gustaaf W. van Imhoff, Joost S.P. Vermaat, Eric A.F. Marijt, Otto Visser, Caroline Mandigers, Yavuz M. Bilgin, Aart Beeker, Mark F. Durian, Bas P. van Rees, Lara H. Bohmer, Lidwine W. Tick, Rinske S. Boersma, Tjeerd J.F. SnijdersHarry C. Schouten, Harry R. Koene, Eva de Jongh, Nathalie Hijmering, Arjan Diepstra, Anke van de Berg, Anne I.J. Arens, Julia Huijbregts, Otto Hoekstra, Josee M. Zijlstra, Daphne de Jong, Marie José Kersten

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

atients with MYC-rearrangement positive large B-cell lymphoma (MYC+ LBCL) have an inferior prognosis following standard first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) compared to patients without MYC rearrangement. Although intensive chemotherapy regimens yield higher remission rates, toxicity remains a concern. Lenalidomide is an oral immunomodulatory drug which downregulates MYC and its target genes thereby providing support using lenalidomide as additional therapeutic option for MYC+ LBCL. A phase II trial was conducted evaluating the efficacy of lenalidomide (15 mg day 1-14) in combination with R-CHOP (R2CHOP) in newly diagnosed MYC+ LBCL patients identified through a nationwide MYCFISH screening program. The primary endpoint was complete metabolic response (CMR) on centrally reviewed 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computer tomography (CT)-scan at end-of-treatment. Secondary endpoints were overall survival (OS), disease-free survival (DFS) and event-free survival (EFS). Eighty-two patients with stage II-IV MYC+ LBCL were treated with six cycles of R2CHOP. At end of treatment, 67% (95% Confidence interval [CI]: 58-75) of the patients reached CMR. With a median follow-up of 25.4 months, 2-year estimates for OS, DFS, EFS were 73% (95% CI: 62-82), 75% (95% CI: 63-84) and 63% change to: (95% CI: 52-73) respectively. In this prospective trial for newly diagnosed MYC+ LBCL patients, we found that administering R2CHOP was safe, and yields comparable CMR and survival rates as in studies applying more intensive chemotherapy regimens. Hence, these findings offer new prospects for MYC+ LBCL patients and warrant comparison in prospective randomized clinical trials. This trial was registered at www.clinicaltrialsregister.eu (#2014-002654-39).

Original languageEnglish
Pages (from-to)2805-2812
Number of pages8
JournalHaematologica
Volume105
Issue number12
DOIs
Publication statusPublished - Dec 2020

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