Real-World Outcomes of Polatuzumab Vedotin with Bendamustine and Rituximab As Salvage and Bridge Therapy to CAR T-Cell Treatment in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Background

Polatuzumab vedotin (Pola) combined with bendamustine and rituximab (BR) represents a promising salvage therapy for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Considering that patients with R/R DLBCL are often older and frailer than those typically enrolled in clinical trials, there is a need for real-world data to evaluate the feasibility and efficacy of Pola-BR in this clinical setting. However, there have been limited analyses reporting real-world outcomes following the use of Pola-BR in clinical practice.

Methods

This single-center real-world study analyzed patients who received Pola-BR either as a salvage therapy or as a bridge to chimeric antigen receptor (CAR) T-cell therapy between April 2021 and April 2024. The primary outcome measure was the complete response (CR) rate following Pola-BR treatment, while secondary measures included progression-free survival (PFS) and overall survival (OS) after the initiation of Pola-BR. Outcomes were compared between two groups: 1) patients receiving Pola-BR as salvage therapy for R/R DLBCL, including those with post-CAR T-cell failure, and 2) patients receiving Pola-BR as bridging therapy prior to CAR T-cell therapy.

Results

A total of 53 patients received Pola-BR during the study period: 40 as salvage therapy and 13 as bridge therapy. The median age of patients in the salvage therapy group was 59 years (range: 29-87), with an ECOG performance status of 1 (range: 0-3). These patients had a median of 4 previous treatments (range: 1-10), with 13 experiencing relapse or progression after CD19 CAR T-cell therapy. The CR rate in the salvage therapy group was 36.6% (15/41), with a median treatment duration of 2 cycles (range: 1-8). PFS in the salvage group was 2.9 months, and only 10 patients completed the planned salvage therapy. Hematologic toxicities were primarily grade 3-4 (93%, 37/40), while non-hematologic toxicities were mainly grade 1-2 (23%, 9/40); no treatment-related deaths occurred.

The bridging therapy group had similar characteristics to the salvage therapy group, though not statistically significant, with a lower median age of 53 years (range: 31-75) and fewer previous treatments (median: 3, range: 2-5). The CR rate after bridging therapy was 38.5% (5/13) before CAR T-cell therapy. Of those achieving CR with Pola-BR bridge therapy, 80% (4/5) maintained CR post-CAR T-cell therapy, with only one patient experiencing CNS progression. All patients who received CAR T-cell therapy after bridge therapy survived. Hematologic toxicities during one cycle of Pola-BR were manageable, with grade 3/4 toxicities in 46% (6/13) of patients, and non-hematologic toxicities were mostly grade 1/2 (15%, 2/13) and grade 3 (7.7%, 1/13).

Conclusion

The efficacy of Pola-BR is limited in heavily pre-treated patients, especially those who have failed CAR T-cell therapy. However, Pola-BR shows promise as a bridging therapy to CAR T-cell therapy, with the ability to induce CR with minimal cycles and manageable toxicity. Further studies are needed to confirm these findings and refine treatment protocols to enhance patient outcomes.

Kim:Kyowa-Kirin: Research Funding; Donga: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Sanofi: Research Funding; Boryong: Research Funding; BeiGene: Research Funding.