Brentuximab vedotin in combination with lenalidomide and rituximab in R/R DLBCL – results from the open part of the ECHELON-3 study

Introduction

The treatment outcomes for patients with R/R DLBCL who are not suitable for hematopoietic stem cell transplant (ASCT) or CAR-T therapy are unfavorable. The BV-len-R combination showed promising efficacy in this indication in a phase I study, where the overall response rate (ORR) was 57%, the median progression-free survival (PFS) was 10.2 months, and the median overall survival (OS) was 14.3 months.

Study Progress and Evaluated Patient Population

In the open run-in phase of the randomized double-blind placebo-controlled ECHELON-3 study, patients with R/R DLBCL after ≥ 2 lines of previous treatment, who were not suitable for ASCT or CAR-T therapy, received brentuximab vedotin (1.2 mg/kg i.v.) and rituximab (375 mg/m² i.v. or 1400 mg s.c.) every 3 weeks and lenalidomide (20 mg p.o. once daily). The efficacy of the treatment was evaluated based on PET/CT scans performed at 6-week intervals.

Ten patients with an average age of 70.5 years (70% men) were included. After a median follow-up of 7.2 months, the median treatment exposure duration was 3.3 months. The performance status of patients according to ECOG was 0 (40%) or 1 (60%). The median number of previous treatment lines was 3 (range 2–6). No patient had previously undergone ASCT, and previous CAR-T therapy had failed in 60% of enrolled patients. CD30 expression < 1% was found in 60% of patients.

Results

Adverse events occurred in all treated patients. Fatigue (50%), anemia (40%), constipation (40%), decreased appetite, diarrhea, dyspnea, hypokalemia, nausea, peripheral edema, and pneumonia (all 30%) were reported with a frequency of > 20%. Serious adverse events were recorded in 70% of patients, most commonly pneumonia. Dose adjustment of one of the drugs in the evaluated combination occurred in 80% of patients, most often due to anemia, neutropenia, peripheral neuropathy, and pneumonia. 40% of patients discontinued treatment.

The ORR was 70%, which includes 50% of patients with complete metabolic remission. A response to treatment was observed in both patients with and without CD30 expression and in 4 out of 6 patients after previous CAR-T therapy failure. The median duration of therapeutic response was 5.6 months (range 0.9–12.6).

Conclusion

The brentuximab vedotin/lenalidomide/rituximab triplet is effective in R/R DLBCL, with an acceptable safety profile. Efficacy was observed in a heavily pre-treated population, including patients with and without CD30 expression, and in those with prior failed CAR-T therapy. Patient enrollment is currently underway for the double-blind phase of the study, in which participants are randomized to add brentuximab vedotin or placebo to lenalidomide and rituximab.

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Source: Bartlett N. L., Yasenchak C. A., Ashraf K. K. et al. Brentuximab vedotin in combination with lenalidomide and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma: safety and efficacy results from the safety run-in period of the phase 3 ECHELON-3 study. EHA 2022, abstract P1178. J Clin Oncol 2022 Jun 1; 40 (16_suppl.): 7559, doi: 10.1200/JCO.2022.40.16_suppl.7559.