A chemotherapy-free immunomodulatory treatment with lenalidomide and rituximab (R2) achieves high rates of molecular response in patients with previously untreated follicular lymphoma, according to research in Blood Advances.

Typical first-line treatment for advanced follicular lymphoma includes rituximab plus immunochemotherapy. Despite initial response, recurrent relapse is characteristic of this disease. Minimal residual disease (MRD) detectable after initial treatment indicates a longer progression-free survival (PFS).

Investigators for the RELEVANCE study (ClinicalTrials.gov Identifier: NCT01650701) measured MRD in a subset of patients the phase 3 clinical trial to compare the molecular response of patients receiving R2 vs rituximab and chemotherapy (R-chemo). They also evaluated the predictive value of MRD for estimating PFS. The primary endpoints of the analysis were complete response at 120 weeks and PFS.

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Patients in the RELEVANCE trial assigned to the R2 arm and received 18 cycles of lenalidomide plus rituximab, followed by rituximab maintenance therapy. Patients in the chemotherapy arm received 1 of 3 standard rituximab-based chemotherapy regimens followed by maintenance with rituximab. 

Patients with a detectable BCL2-JH translocation were assessed for MRD using polymerase chain reaction at diagnosis. After testing patients for the translocation, 222 patients were included in the analysis: 122 in the R2 group and 100 in the R-chemo group. 

At the end of the induction period (week 24), 98% of patients achieved complete molecular response (CMR) measured in peripheral blood and 78% had CMR measured in bone marrow.  

The investigators noted that molecular disease detection in peripheral blood and/or bone marrow at week 24 significantly affected PFS (P =.0063); the rate of 3-year PFS was 84% for patients in CMR and 55% for patients with detectable MRD (hazard ratio, 2.6; 95% CI, 1.27-5.13; P =.015). No matter the treatment received, PFS was lower in patients with detectable MRD. Patients in the R2 arm reached CMR more frequently than patients in the R-chemo arm (90% vs. 77%). However, the PFS was similar in both groups. 

One possible limitation of the study is that the patients selected for analysis may have had more severe disease than the overall patient population of the RELEVANCE trial. However, PFS was similar across both arms and similar to PFS observed for all patients in the larger trial. 

“We feel that showing that there was no difference between the 2 arms in this higher-risk population further underlines the effectiveness of the chemotherapy-free treatment in first-line FL patients needing therapy,” the investigators wrote.

The authors concluded that R2 immunomodulatory induction treatment leads to a better molecular response than R-chemo. They also suggested that MRD be evaluated further for its prognostic value in predicting PFS.


Delfau-Larue MH, Boulland ML, Beldi-Ferchiou A, et al. Lenalidomide/rituximab induces high molecular response in untreated follicular lymphoma: LYSA ancillary RELEVANCE study. Blood Adv. 2020;4(14):3217-3223.