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.