Penpulimab and lenalidomide in combination with standard of care chemoimmunotherapy demonstrates promising safety and efficacy in diffuse large B-cell lymphoma

1. Penpulimab and lenalidomide in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx regimen) is safe, tolerable, and shows antitumour activity in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Evidence Rating Level: 2 (Good)

Approximately 40% of patients with DLBCL, the most common subtype of non-Hodgkin lymphoma, experience R/R disease after the first line of treatment. R-GemOx is a commonly used chemoimmunotherapy regimen for R/R DLBCL. Lenalidomide, an immunomodulatory drug, has been shown to have good efficacy in treating DLBCL. Furthermore, synergistic effects have been shown in penpulimab, a PD-1 inhibitor, and lenalidomide combinations. The authors of this multi-center, single-arm, phase 2 trial hypothesized R-GemOx in combination with penpulimab and lenalidomide (R2-GemOx-PD1i) would be safe and efficacious. Patients were included if they were 18-80 years, had DLBCL, and failed first-line rituximab-based chemotherapy. 54 patients (median [range] years, 69 (19-80); 42.6% female) were evaluated. Twenty-nine patients (53.7%) were refractory, and 25 patients (46%) were relapsed. 38 patients were treated with R2-GemOx-PD1i without intent for consolidation with autologous stem cell transplantation (ASCT). This arm had an overall response rate (ORR) and complete response rate (CRR) of 63.2% and 52.6%, respectively. Patients had a median progression-free survival (PFS) of 21.2 months, and the median overall survival (OS) was not reached. 16 patients were treated with R2-GemOx-PD1i as a bridge to ASCT. This arm had an ORR and CRR of 75.0% and 68.8%, respectively. Neither PFS nor OS were reached. The most frequent adverse events were neutropenia (36/54, 66.6%), anemia (32/54, 59.2%) and thrombocytopenia (15/54, 27.7%). There were 14 deaths: one due to COVID-19 infection and 13 due to disease progression. All adverse events were manageable, and no deaths were considered to be treatment-related.

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