Rituximab/Lenalidomide Combo Shows Promise for Indolent Lymphomas

David J. Andorsky, MD

Treatment with rituximab (Rituxan) plus lenalidomide (Revlimid) followed by maintenance therapy demonstrated promising clinical activity for patients with relapsed/refractory indolent non-Hodgkin's lymphoma, according to findings from the phase IIIb MAGNIFY study.

In the study, the objective response rate (ORR) for patients with follicular lymphoma was 66% with rituximab plus lenalidomide, which included a 38% rate of complete response (CR) or unconfirmed CR (CRu). In those with marginal zone lymphoma (MZL), the ORR with the chemotherapy-free combination was 66% and the CR/CRu was 44%.

Results from the ongoing study were presented at the 2017 ASCO Annual Meeting and the 2017 International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland.^1,2

"The chemotherapy-free combination of lenalidomide and rituximab, with complementary mechanisms of action that are thought to enhance antibody dependent cellular cytotoxicity, continues to show encouraging activity and a tolerable safety profile in indolent lymphomas, and particularly in difficult-to-treat patient subsets," co-principal investigator David J. Andorsky, MD, medical oncologist at the Rocky Mountain Cancer Centers, said in a statement. "These results in patients who had failed multiple therapies or relapsed early, as well as the activity in marginal zone patients merit further study in this area of indolent lymphoma."

The trial enrolled patients with follicular lymphoma (n = 160) and MZL (n = 38) to receive induction therapy with lenalidomide and rituximab for 12 cycles followed by randomization to continued maintenance therapy for 18 cycles with lenalidomide plus rituximab or rituximab alone.

The median age of patients across groups was 65 years and all had an ECOG performance status of 0 or 1. In the follicular lymphoma group, patients had received a median of 2 prior therapies (range, 0-9) and in the MZL group patients had received 1 prior therapy (range, 1-4). In the follicular lymphoma group, 52 patients had early relapse (within 2 years of diagnosis) and 50 patients were double-refractory (refractory to rituximab and an alkylating agent). In the MZL group, patients had nodal MZL (n = 18), splenic MZL (n = 10), and mucosa-associated lymphoid tissue (MALT) lymphoma (n = 10).

In the follicular lymphoma arm, the median follow-up time was 10.2 months (9 months for double refractory and 12.1 months for the early relapsing patients). In the double refractory group and early relapse arm, the ORR was 45% and 47%, respectively. The CR/CRu rate was 21% in both groups. In those with high-risk follicular lymphoma, the ORR was 66%.

The 1-year progression-free survival (PFS) rate was 70% with rituximab and lenalidomide. In the double refractory and early relapse groups, the 1-year PFS rates were 65% and 49%, respectively. In the early relapse group, the 1-year PFS was similar in those who received frontline rituximab/chemotherapy (n = 39; 52%) and those received a non-rituximab chemotherapy regimen (n = 13; 44%). In high-risk patients, the 1-year PFS rate was 70%.

In patients with MZL, the median follow-up was 13.8 months and the median duration of response was not yet reached. In evaluable patients with nodal MZL (n = 14), the ORR was 57% and the CR/CRu rate was 57%. In those evaluable with splenic MZL (n = 8), the ORR was 63% with the combination and the CR rate was 25%. In the MALT group, the ORR was 80% and the CR/CRu rate was 40%.

In the MZL group, the most common grade 3/4 AEs were neutropenia (32%), thrombocytopenia (16%), and leukopenia (11%).In the double refractory and early relapse follicular lymphoma arms, respectively, the most common grade 3/4 treatment-emergent adverse events (TEAEs) were neutropenia (42% vs 37%), leukopenia (8% vs 10%), thrombocytopenia (8% vs 4%), and lymphopenia (6% vs 4%). Other grade 3/4 AEs in the double refractory and early relapse arms, respectively, included febrile neutropenia (4% vs 4%) and thrombosis (2% vs 0%).

"There was no tumor lysis syndrome, tumor flare reaction, or hepatic disorders," Andorsky noted when presenting the findings at ASCO.

An open-label phase III study, known as RELEVANCE, is currently comparing rituximab plus lenalidomide with rituximab and chemotherapy for patients with previously untreated follicular lymphoma. In the study, rituximab combinations include R-CHOP, R-CVP, and BR. Lenalidomide is being administered at 20 mg for 6 cycles followed by 10 mg, if there is a CR. Results from this study, which started in 2011, are expected soon (NCT01476787). Additionally, recruitment in the MAGNIFY study remains ongoing (NCT01996865).

References

1. Andorsky DJ, Yacoub A, Melear JM, et al. Phase IIIb randomized study of lenalidomide plus rituximab (R2) followed by maintenance in relapsed/refractory NHL: Analysis of patients with double-refractory or early relapsed follicular lymphoma (FL). J Clin Oncol. 2017;35 (suppl; abstr 7502).
2. Coleman M, Andorsky DJ, Yacoub A, et al. Phase IIIB study of lenalidomide plus rituximab followed by maintenance in relapsed or refractory NHL: analysis of marginal zone lymphoma. Presented at: 14th International Conference on Malignant Lymphoma; June 14-17, 2017; Lugano, Switzerland. Abstract 139. DOI: 10.1002/hon.2437_138.