PD-1 blockade for diffuse large B-cell lymphoma after autologous stem cell transplantation

Abstract

Disease relapse remains the leading cause of failure after autologous stem cell transplantation (ASCT) for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). We conducted a phase 2, multicenter, single-arm study of the anti–PD-1 monoclonal antibody pembrolizumab given after ASCT in patients with chemosensitive DLBCL, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary endpoint) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. Twenty-nine patients were treated on this study; 62% completed all 8 cycles. Seventy-nine percent of patients experienced at least one grade 3 or higher adverse event, and 34% experienced at least one grade 2 or higher immune-related adverse event. Overall, 59% of patients were alive and progression free at 18 months, which did not meet the primary endpoint. The 18-month overall survival was 93%. In conclusion, pembrolizumab was successfully administered as post-ASCT consolidation in patients with R/R DLBCL, but the PFS did not meet the protocol-specific primary objective and therefore does not support a larger confirmatory study. This trial was registered at www.clinicaltrials.gov as #NCT02362997.

2021 Update on Diffuse large B cell lymphoma: A review of current data and potential applications on risk stratification and management

“…Frigault et al evaluated the use of the anti–PD‐1 monoclonal antibody pembrolizumab after ASCT in patients with chemosensitive DLBCL in a phase 2, multicenter, single‐arm study 57 . Of a total of 29 patients treated, only 62% completed all eight planned cycles of pembrolizumab, and 79% experienced grade 3 or higher adverse event and 34% grade 2 or higher immune‐related adverse event.…”

New agents and regimens for diffuse large B cell lymphoma

“…Also, PD-1 blockade after ASCT was believed to leverage immune landscapes to decrease minimal residual disease. However, data from a phase 2 study showed that pembrolizumab consolidation given after ASCT did not improve the 18-month PFS rate (59%) [ 49 ]. Just as rituximab does not provide clinical benefits when used as post-ASCT maintenance, checkpoint inhibitors face the same challenge.…”

Immune-Checkpoint Inhibitors in B-Cell Lymphoma

“…Most DLBCL patients were initially thought to be not amenable to PD-1 blockade since PDL-1/2 alterations are nonfrequent in this disease, and, accordingly, PD-1 blockade therapy has been disappointing to date in R/R DLBCL and FL. While several ongoing clinical trials are evaluating the use of pembrolizumab in different DLBCL subtypes, this antibody failed to improve PFS in ASCT-relapsed patients [ 102 ]. Similarly, a first phase-1b dose-escalation cohort expansion study evaluating nivolumab in R/R DLBCL patients (NCT01592370) and a subsequent larger phase-2 study (NCT02038933) in ASCT-relapsed and ASCT-ineligible DLBCL patients reported overall response rates (ORRs) <40% [ 78 , 97 , 100 , 103 ] ( Table 1 ).…”