Polatuzumab as Bridging or Salvage Therapy for Patients With Relapsed/Refractory LBCL

Polatuzumab vedotin was approved in 2019 in combination with bendamustine and rituximab for patients with relapsed or refractory large B-cell lymphoma (LBCL). It showed value in bridging to chimeric antigen receptor (CAR) T-cell therapy and allogeneic hematopoietic cell transplantation (alloHCT) and as a salvage therapy in patients who were not eligible for intensive consolidative treatments, according to research findings published in Blood Advances.

The analysis involved 105 patients with relapsed/refractory LBCL who had received polatuzumab under a compassionate use program in Germany since 2019. As such, these patients were treated with polatuzumab prior to its approval in the country in 2020. Patients received polatuzumab as either a salvage treatment (n=54) or as a bridging therapy (n=51) to CAR T-cell therapy or alloHCT.

At baseline, patients had received a median of three previous lines of therapy. Approximately 84.3% of patients in the bridging cohort and 87% of patients in the salvage cohort had disease that was refractory to their last therapy.

A significantly greater proportion of patients in the bridging cohort had experienced failure with autologous HCT (31.4% vs. 9.3%; p=0.007). The median age of individuals in the salvage cohort was significantly higher than those in the bridging cohort (73.5 vs. 61 years, respectively).

In the salvage cohort, most patients were treated with polatuzumab in combination with bendamustine (59.3%), while the remaining patients largely received polatuzumab plus rituximab without a chemotherapy backbone. Patients in the overall salvage group underwent a median of four administered polatuzumab cycles, with 40.7% of patients (n=22) completing six cycles of treatment.

The best responses achieved with polatuzumab in the salvage cohort included a complete response in 14.8% of patients (n=8) and a partial response or clinical response in 33.3% of patients (n=18). The overall response rate in this group was 48.1% (TABLE 1).

At six months, progression-free survival (PFS) from the start of polatuzumab was 27.7% (95% CI 17.9-42.6), while 12-month PFS was 8.0% (95% CI 1.7-38.3) over a median follow-up of 7.5 months. Additionally, six-month overall survival (OS) was 49.6% (95% CI 37.4-65.9), whereas 12-month OS was 12.6% (95% CI 4.1-38.9). The median OS was numerically higher in patients who had received two prior lines of therapy versus patients with three or more prior lines of treatment (6.7 vs. 3.1 months, respectively; hazard ratio [HR]=1.4; 95% CI 0.7-2.8; p=0.3).

In a multivariate analysis, having three or more lines of prior therapy had a significantly adverse impact on PFS compared with two lines (HR=2.3; 95% CI 1.1-4.4; p=0.02). Additionally, response to last pretreatment represented an independent predictor of OS (HR=2.1; 95% CI 1.04-4.3; p=0.04) and PFS (HR=2.4; 95% CI 1.3-4.6; p=0.007).

The bridging cohort received a median of two cycles of a polatuzumab-containing regimen, which was significantly lower compared with the salvage group (p=0.001). Approximately 68.3% of patients in the bridging cohort underwent CAR T-cell therapy. Three out of five patients with disease progression during polatuzumab experienced remission following CAR T-cell therapy.

In the bridging group of patients who subsequently received CAR T-cell therapy, six-month OS was 77.9% (95% CI 60.7-100), while 12-month OS was 58.5% (95% CI 31.5-100). In contrast, six-month OS for patients who did not reach CAR T-cell therapy was 22% (95% CI 6.8-70.7).

The six-month PFS and OS rates from start of polatuzumab within the bridging group were 29.6% (95% CI 17.2-51.1) and 61.8% (95% CI 47.6-80.2), respectively, over a median follow-up of 7.2 months (TABLE 2).

Cytopenias were the most common all-grade and grade 3 to 4 adverse events. Additionally, 15.4% of patients in the salvage cohort and 6.1% of patients in the bridging cohort experienced grade 3 to 4 febrile neutropenia.

Given the study’s retrospective nature, the researchers noted that the analysis lacked predefined image-based response assessment. Additionally, the relatively short follow-up duration of patients may limit the long-term assessment of polatuzumab’s effects in this population.

The study authors reported no relevant conflicts of interest.

Reference

Liebers N, Duell J, Fitzgerald D, et al. Polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas. Blood Adv. 2021;5(13):2707-2716.