Polatuzumab Vedotin Plus Rituximab and Lenalidomide Efficacy Among Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Phase 1b/2 Trial Results

The combination of polatuzumab vedotin with rituximab and lenalidomide therapy provided some patients with clinical benefit, and demonstrated a tolerable safety profile among patients with diffuse large B-cell lymphoma (DLBCL), according to a phase 1b/2 study. However, the combination therapy did not meet the pre-specified activity threshold set by the study investigators.

This open-label, multicenter, single-arm study evaluated the safety and efficacy of this treatment combination in patients with relapsed or refractory (R/R) DLBCL at 19 sites across the United States, Spain, and the United Kingdom. Eligible patients included those 18 years or older, if they had histologically documented CD20-positive R/R DLBCL, an Eastern Cooperative Oncology Group performance status of 2 or lower, had received at least 1 previous line of chemoimmunotherapy, including an anti-CD20 agent, and were ineligible for stem-cell transplantation. 

In the dose-escalation phase, the primary safety objective was identification of the maximum tolerated dose through incidence of dose-limiting toxic effects. Additionally, the primary efficacy outcome of the dose-expansion phase was Independent Review Committee (IRC)-assessed complete response rate (CRR) at end of induction, based on PET-CT. 

In this study, 57 patients were enrolled; the median previous lines of therapy was 2 (interquartile range [IQR] 1 to 3]). Additionally, 18 participants were included in phase 1b and 39 were included in phase 2. Phase 1b confirmed a 20 mg recommended phase 2 dose for lenalidomide.

Patients received 6 total 28-day cycles of induction treatment with intravenous rituximab 375 mg/m² intravenous polatuzumab vedotin 1.8 mg/kg (all cohorts) plus oral lenalidomide at the following doses: 10 mg (cohort A); 15 mg (cohort B); and 20 mg (cohort C). Rituximab and polatuzumab vedotin were administered on day 1 and lenalidomide on days 1 to 21 of each 28-day cycle. During the dose-expansion phase, patients received 6 total 28-day cycles of polatuzumab vedotin with rituximab and lenalidomide at the recommended phase 2 dose established during dose escalation. In both phases, patients with a complete response (CR) or partial response (PR) at the end of induction were eligible for post-induction therapy with rituximab 375 mg/m² on day 1 and lenalidomide 10 mg/day on days 1 to 21 of each 28-day cycle for a maximum of 6 cycles. 

Results demonstrated that, following a median follow-up of 11.8 months (IQR 4.7 to 25.8), the CRR, as assessed by the IRC, was 31% (90% confidence interval [CI], 20 to 43). The most notable grade 3 to 4 adverse events were neutropenia (35 [61%] of 57) and thrombocytopenia (8 [14%] of 57). Serious adverse events were reported in 23 (40%) of 57 patients. 1 patient died due to neutropenic sepsis.

Pau Abrisqueta, PhD, Hospital Vall D'Hebron, Barcelona, Spain, and colleagues concluded that although this treatment did not meet the prespecified activity threshold, “some patients derived clinical benefit and the regimen had a tolerable safety profile in patients with relapsed or refractory diffuse large B-cell lymphoma.”

Source:

Abrisqueta P, González-Barca E, Panizo C, et al. Polatuzumab vedotin plus rituximab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma: A cohort of a multicentre, single-arm, phase 1b/2 study. Lancet Hematol. Published online January 5, 2024. doi: 10.1016/S2352-3026(23)00345-9