Disclosures: NCI supported the study. Nowakowski reports research funding from Bristol Myers Squibb, Celgene, MorphoSys AG, NanoString Technologies, Roche and Seagen; and consultant/advisory roles with Bristol Myers Squibb, Celgene, Debiopharm Group, Gilead Sciences, Genentech, Karyopharm Therapeutics, Kite, MorphoSys AG and Roche Selvita. Please see the study for all other authors’ relevant financial disclosures.
March 01, 2021
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Lenalidomide plus R-CHOP shows promise among patients with diffuse large B-cell lymphoma

Disclosures: NCI supported the study. Nowakowski reports research funding from Bristol Myers Squibb, Celgene, MorphoSys AG, NanoString Technologies, Roche and Seagen; and consultant/advisory roles with Bristol Myers Squibb, Celgene, Debiopharm Group, Gilead Sciences, Genentech, Karyopharm Therapeutics, Kite, MorphoSys AG and Roche Selvita. Please see the study for all other authors’ relevant financial disclosures.
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The addition of lenalidomide to R-CHOP chemotherapy improved survival outcomes among patients with newly diagnosed diffuse large B-cell lymphoma, according to study results published in Journal of Clinical Oncology.

The combination regimen showed benefit particularly among patients with the activated B-cell DLBCL subtype.

The addition of lenalidomide to R-CHOP chemotherapy improved survival outcomes among patients with newly diagnosed diffuse large B-cell lymphoma.

R-CHOP chemotherapy has been a front-line standard in DLBCL for nearly 20 years, despite multiple attempts and clinical trials to improve this treatment. Approximately 40% of patients will relapse after R-CHOP within the first 2 years and outcomes are poor — hence the need for new treatment,” Grzegorz S. Nowakowski, MD, a hematologist-oncologist in the division of hematology at Mayo Clinic, told Healio. “Lenalidomide [Revlimid, Celgene] as a single agent has shown significant activity in relapsed and refractory DLBCL, and we and others have shown that combination of lenalidomide with R-CHOP is feasible and produced significantly improved results in single-arm studies, particularly in those with the activated B-cell DLBCL subtype, which is what led us to the current randomized phase 2 study.”

Grzegorz S. Nowakowski, MD
Grzegorz S. Nowakowski

Nowakowski and colleagues randomly assigned 280 patients (median age, 66 years; range, 24-92) with untreated DLBCL to lenalidomide plus R-CHOP (R2CHOP; n = 145) or R-CHOP (n = 135). Most patients (70%) had stage IV disease, and all had an International Prognostic Index (IPI) of 2 or higher (34% IPI2, 43% IPI3, and 24% IPI4 or IPI5).

Ninety-four patients (40%) had the activated B-cell DLBCL subtype.

R-CHOP consisted of six cycles of 375 mg/m2 rituximab (Rituxan; Genentech, Biogen), 750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin and 1.4 mg/m2 vincristine, all on day 1, and 100 mg/m2 prednisone on days 1 to 5 of each cycle every 21 days. Patients in the experimental group also received 25 mg of lenalidomide on days 1 through 10 of each cycle.

PFS served as the primary endpoint, with a co-primary endpoint of PFS among those with the activated B-cell DLBCL subtype. Overall response rate, complete response rate and OS served as secondary endpoints.

Median follow-up was 3 years.

Results showed a higher ORR with R2CHOP compared with R-CHOP (97% vs. 92%), as well as a higher complete response rate (73% vs. 68%), although the differences did not reach statistical significance.

Researchers reported a 34% reduction in the risk for disease progression or death with R2CHOP vs. R-CHOP (HR = 0.66; 95% CI, 0.43-1.01). Both 3-year PFS (73% vs. 62%; one-sided P = .03) and OS (83% vs. 75%; HR = 0.67; one-sided P = .05) also favored R2CHOP.

Patients with the activated B-cell DLBCL subtype who received R2CHOP had a PFS HR of 0.67.

Myelosuppression appeared more common in the R2CHOP group, according to the researchers, as did grade 3 or higher adverse events, including diarrhea (6% vs. 1%), anemia (29% vs. 20%), febrile neutropenia (25% vs. 14%), thrombocytopenia (34% vs. 13%) and electrolyte abnormalities (5% vs. 2%).

“This study suggests that the addition of lenalidomide may indeed improve outcomes over R-CHOP alone in all-comers with DLBCL, although the effect was driven largely by the activated B-cell DLBCL subtype,” Nowakowski said. “As of now, despite these encouraging results, clinical practice should not be changed as a larger soon-to-be-published update of the ROBUST study will not show consistent results, as there were no differences with lenalidomide.”

However, multiple differences between the two studies — including different doses, the fact that ROBUST targeted only the activated B-cell DLBCL subtype, and likely significant delays from treatment to diagnosis — may explain the different results, Nowakowski added.

“The R2CHOP backbone used in our current study is used in the ongoing First-Mind trial, which has shown feasibility of tafasitamab [MorphoSys AG] plus R-CHOP, hence providing the foundation for randomized study of tafasitamab plus R2CHOP vs. R-CHOP,” Nowakowski said. “Of note, the combination of tafasitamab plus lenalidomide was recently granted accelerated approval in relapsed or refractory DLBCL, in which the combination showed both a high response rate and durability of response.

“Our current study provides insights into the design of future trials mainly in avoiding any biomarkers or other screening procedures, which could delay putting sicker, rapidly progressing patients on a clinical trial. This likely affected the results but made our study successful,” Nowakowski added.

For more information:

Grzegorz S. Nowakowski, MD, can be reached at Mayo Clinic, 200 First Street SW, Rochester, MN 55901; email: nowakowski.grzegorz@mayo.edu.