Treatment of patients with MYC rearrangement positive large B-cell lymphoma with R-CHOP plus lenalidomide: results of a multicenter HOVON phase II trial
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,
Erik A.F. Marijt,
Otto Visser,
Caroline Mandigers,
Yavuz M. Bilgin,
Aart Beeker,
Mark F. Durian,
Bas van Rees,
Lara H. Bohmer,
Lidwine W. Tick,
Rinske S. Boersma,
Tjeerd J.F. Snijders,
Harry C. Schouten,
Harry R. Koene,
Eva de Jongh,
Nathalie Hijmering,
Arjan Diepstra,
Anke van den Berg,
Anne I.J. Arens,
Julia Huijbregts,
Otto Hoekstra,
Josee M. Zijlstra,
Daphne de Jong,
Marie José Kersten
Affiliations
Martine E.D. Chamuleau
Department of Hematology, Amsterdam UMC, location VU University Medical Center, the Netherlands;
Coreline N. Burggraaff
Department of Hematology, Amsterdam UMC, location VU University Medical Center, the Netherlands;
Marcel Nijland
Department of Hematology, UMC Groningen, University of Groningen, Groningen, the Netherlands;
Katerina Bakunina
Dept. of Hematology, HOVON Data Centre, Erasmus MC Cancer Institute, Rotterdam, The Netherlands;
Rogier Mous
Dept. of Hematology, UMC Utrecht Cancer Centre, University Medical Centre Utrecht, the Netherlands;
Pieternella J. Lugtenburg
Department of Hematology Erasmus MC Cancer Institute, Rotterdam, the Netherlands;
Daan Dierickx
Department of Hematology, University Hospitals Leuven, Leuven, Belgium;
Gustaaf W. van Imhoff
Department of Hematology, UMC Groningen, University of Groningen, Groningen, the Netherlands;
Joost S.P. Vermaat
Department of Hematology, Leiden University Medical Centre, Leiden, the Netherlands;
Erik A.F. Marijt
Department of Hematology, Leiden University Medical Centre, Leiden, the Netherlands;
Otto Visser
Department of Hematology, Oncology Centre Isala, Zwolle, the Netherlands;
Caroline Mandigers
Department of Hematology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands;
Yavuz M. Bilgin
Department of Internal Medicine, Admiraal de Ruijter Hospital Goes, the Netherlands;
Aart Beeker
Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, the Netherlands;
Mark F. Durian
Department of Internal Medicine, Tweesteden Hospital, Tilburg, the Netherlands;
Bas van Rees
Department of Internal Medicine, Tjongerschans Hospital, Heerenveen, the Netherlands;
Lara H. Bohmer
Department of Internal Medicine, Haga Hospital, the Netherlands;
Lidwine W. Tick
Department of Internal Medicine, Maxima Medisch Centrum, Veldhoven, the Netherlands;
Rinske S. Boersma
Department of Internal Medicine, Amphia Hospital, Breda, the Netherlands;
Tjeerd J.F. Snijders
Department of Hematology, Medisch Spectrum Twente, Enschede, the Netherlands;
Harry C. Schouten
Department of Hematology, Maastricht UMC, Maastricht, the Netherlands;
Harry R. Koene
Department of Internal Medicine, St Antonius Hospital, Nieuwegein, the Netherlands;
Eva de Jongh
Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, the Netherlands;
Nathalie Hijmering
Department of Pathology, Amsterdam UMC, location VU University Amsterdam, the Netherlands;
Arjan Diepstra
Dept. of Pathology and Medical Biology, UMC Groningen, University of Groningen, the Netherlands;
Anke van den Berg
Dept. of Pathology and Medical Biology, UMC Groningen, University of Groningen, the Netherlands;
Anne I.J. Arens
Dept. Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands;
Julia Huijbregts
Department of Radiology and Nuclear Medicine, Gelre Hospital, Apeldoorn, the Netherlands;
Otto Hoekstra
Dept. of Radiology and Nuclear Medicine, Amsterdam UMC, VU University Amsterdam, the Netherlands;
Josee M. Zijlstra
Department of Hematology, Amsterdam UMC, location VU University Medical Center, the Netherlands;
Daphne de Jong
Department of Pathology, Amsterdam UMC, location VU University Amsterdam, Amsterdam, the Netherlands;
Marie José Kersten
Dept of Hematology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, the Netherlands
Patients 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) as 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 MYC-FISH 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 6 cycles of R2CHOP. At EOT, 67% (confidence interval (CI) 58-75%) of the patients reached CMR. With a median follow-up of 25.4 months, 2-year estimates (95% CI) for OS, DFS, EFS were 73% (62-82%), 75% (63-84%) and 63% (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).
