Patients with relapsed/refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL) who do not benefit from or are ineligible for stem cell transplant and chimeric antigen receptor treatment require new medicines. As single treatments, the CD30-targeted antibody-drug combination brentuximab vedotin (BV) and the immunomodulator lenalidomide (Len) have shown promise efficacy in the group. The findings of a phase 1 dosage expansion experiment testing the combination of BV/Len in rel/ref DLBCL were presented. About 37 patients were given BV every 21 days, with Len given continuously for a total of 16 cycles. The combination’s maximal tolerable dosage was 1.2 mg/kg BV with 20 mg/d Len. The toxicity profile of BV/Len was consistent with their usage as single agents. Because of neutropenia, the majority of patients required granulocyte colony-stimulating factor support.

The overall response rate was 57% (95% CI, 39.6-72.5), the complete response rate was 35% (95% CI, 20.7-52.6), the median duration of response was 13.1 months, the median progression-free survival was 10.2 months (95% CI, 5.5-13.7), and the median overall survival was 14.3 months (95% CI, 10.2-35.6). Response rates were greatest (73%) in patients with CD30+ DLBCL, but did not differ by the cell of origin (P=.96). Mass cytometry was used to identify NK cell growth and phenotypic alterations in CD8+ T-cell subsets in nonresponders. For individuals with rel/ref DLBCL, BV/Len might be a viable therapy option.