Lenalidomide/rituximab induces high molecular response in untreated follicular lymphoma: LYSA ancillary RELEVANCE study

Abstract

Complete molecular response (CMR) after first-line immunochemotherapy reflects treatment efficacy and may predict prognosis in patients with follicular lymphoma (FL). RELEVANCE is the first phase 3 trial comparing the chemotherapy-free regimen lenalidomide/rituximab (R2) vs rituximab/chemotherapy (R-Chemo) in previously untreated FL patients (ClinicalTrials.gov identifier: NCT01650701). The objective of the minimal residual disease (MRD) analysis was to determine the ability of a chemotherapy-free regimen to induce CMR. Of 440 French patients participating in the Lymphoma Study Association (LYSA) RELEVANCE MRD study, all 222 patients with a BIOMED-2-detectable BCL2-JH translocation at diagnosis were analyzed. MRD was quantified by droplet digital polymerase chain reaction with a sensitivity ≤10-4. At week 24 (end of induction treatment), 98% and 78% of patients achieved CMR in peripheral blood (PB) and bone marrow (BM), respectively. Achievement of CMR (in PB and/or BM) had a significant impact on progression-free survival (PFS), with 3-year PFS of 84% and 55% for patients with CMR and detectable MRD, respectively (P = .015). CMR at week 24 was reached more frequently in the R2 arm (105/117; 90%) than in the R-Chemo arm (70/90; 77%) (P = .022). The poor prognostic value in terms of PFS for the persistence of molecular disease was observed irrespective of treatment arm (interaction test, P = .31). In agreement with the clinical results of the RELEVANCE trial, our results show that R2 immunomodulatory treatment in first-line FL can achieve high rates of CMR.

Conflict of interest statement

Conflict-of-interest disclosure: M.-H.D.-L. has received personal fees for scientific lectures from Amgen, Janssen, and Roche and nonfinancial personal support from Celgene during the conduct of the study. P.F. has received personal fees from Roche and Celgene outside of the submitted work. R.-O.C. has received grants for clinical research, honoraria, and travel expenses from, as well as served on advisory boards for, Roche, Gilead Sciences, and Takeda; honoraria and travel expenses from, as well as served on advisory boards for, Bristol Myers Squibb, MSD, and Celgene; and served on advisory boards for, as well as received honoraria from, AbbVie outside of the submitted work. R.H. has received honoraria or consulting fees from Bristol Myers Squibb, MSD, Gilead Sciences, Kite, Roche, Novartis, Janssen, and Celgene. H.T. has received grants and personal fees from Celgene, personal fees and nonfinancial support from Roche, and personal fees from Karyopharm, AstraZeneca, and Bristol Myers Squibb outside of the submitted work. S.L.G. has acted as a consultant for and served on advisory boards for Roche SAS, Janssen-Cilag, Gilead Sciences/Kite, Novartis, Loxo Oncology, AbbVie, and Servier. V.R. has served on advisory boards for Gilead, Infinity, MSD, Bristol Myers Squibb, Epizyme, NanoString, Incyte, and Roche and has received research funding from argenx outside of the submitted work. G.C. has acted as a consultant for, and received honoraria from, Roche and Celgene and has received honoraria from Sanofi, Gilead Sciences, and Janssen during the conduct of the clinical study. G.A.S. has received grants and personal fees from Celgene and Roche during the conduct of the study and has received honoraria from Janssen, as well as acted as a consultant for, and received honoraria from, Gilead Sciences, Celgene, Novartis, Amgen, Servier, Bristol Myers Squibb, Merck, MorphoSys, Roche, Acerta, and Pfizer outside of the submitted work. F.M. has received nonfinancial support from Celgene during the conduct of the study; has served on advisory boards for Celgene, Roche, and Bristol Myers Squibb; has given scientific lectures for Celgene, Roche, and Janssen; has served on the advisory board for Bristol Myers Squibb; and has acted as a consultant for, served on the advisory board of, and given scientific lectures for Gilead Sciences outside of the submitted work. L.Y. has received grants and personal fees from AbbVie, AstraZeneca, Gilead Sciences, Janssen, and Roche. The remaining authors declare no competing financial interests.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Impact of positive MRD at W24 on PFS. PFS by MRD status at W24 evaluated in PB and/or BM (A) or in BM (B). NA, not applicable; Pos, positive.

Figure 2.

Molecular disease in BM samples according to treatment arm. MRD level was quantified using droplet digital PCR, and results are expressed as number of tumor cells/number of analyzed cells. Each dot represents a patient sample. The lines connect the diagnostic and W24 samples from the same patient. CMR was defined as negative MRD PCR with a sensitivity ≥10−4.

Figure 3.

PFS survival in MRD-studied population by treatment arm.