Polatuzumab Effective in R/R DLBCL Patients Ineligible for Stem Cell Transplant

Real-world results show efficacy as stand-alone treatment, CAR T-cell bridging Tx, and after CAR T-cell failure

05/13/2022
Liz Meszaros, Deputy Managing Editor, BreakingMED™
Kevin Rodowicz, DO, Assistant Professor, St. Luke’s University/Temple University
Take Away
  1. Researchers demonstrated the feasibility of polatuzumab vedotin with bendamustine and rituximab (Pola-BR) as a treatment for patients with R/R DLBCL who are ineligible for SCT.

  2. These results also provide preliminary evidence of the efficacy of Pola-BR for CAR T-cell therapy bridging and after CAR T-cell therapy failure, which should be validated in future clinical trials.

Treatment with polatuzumab vedotin with bendamustine and rituximab (Pola-BR) in patients with diffuse large B-cell lymphoma (DLBCL) who are not eligible for stem cell transplantation (SCT) may be effective and feasible as a stand-alone treatment. It could also be used as a bridging treatment to CAR T-cell therapy, and as treatment after CAR T-cell therapy failure, according to real-world results from researchers in the U.K.

Polatuzumab vedotin is an anti-CD79b monoclonal antibody. Results from a previous phase II trial (G029365) had shown superior median progression-free survival (PFS) and overall survival (OS) with Pola-BR compared with bendamustine-rituximab for the treatment of relapsed/refractory DLBCL in patients ineligible for SCT.

"Before regulatory approval in the United Kingdom, Pola-BR was available via the Early Access to Medicines Scheme (EAMS) between June 2019 and January 2020 in line with the intended label. Subsequently, interim funding (from March to August 2020) was provided via the Cancer Drugs Fund (CDF) for Pola-BR because of potential delays in CAR T-cell therapy delivery during the Covid-19 pandemic. We analyzed outcomes of patients treated on these schemes," wrote Michael Northend, of University College Hospital, and Cancer Research United Kingdom, London, and colleagues in a research letter published in Blood Advances.

In this retrospective study, they analyzed data from 133 patients (median age, 72 years; 65.4% male) with relapsed or refractory DLBCL who were ineligible for SCT and those approved to receive CAR T-cell therapy. All patients experienced potential delays in treatment administration during the Covid-19 pandemic.

Treatment with Pola-BR (1.8 mg/kg for a maximum of 6 cycles) was administered on day 1 or 2 of a 28-day cycle. In 40 patients, the goal of treatment with Pola-BR was as bridging to CAR T-cell therapy; in 13, treatment was used as re-induction therapy; in 78 patients, Pola-BR was given as stand-alone treatment; and in two patients, treatment goal was unknown. All were ineligible for SCT due to age (55.1%), comorbidities (21.8%), and insufficient response to previous treatment (17.9%).

In the overall cohort, after a median follow-up of 7.7 months, the best objective response rate (ORR) was 57.0% (CR, 31.6%), median PFS was 4.8 months (95% CI, 3.7-9.3 months), and median OS was 8.2 months (95% CI, 5.9-14.3 months).

In patients treated with Pola-BR as a bridge to delayed CAR T-cell treatment, 77.5% received cell infusion, five died as a result of progressive disease, and one died as a result of infection during bridging. For two patients, infusion was pending, and in one, data were missing. In 36 of these 40 patients (90.0%), leukapheresis was performed before bridging (after at least one cycle of Pola-BR in three patients). Best ORR to Pola-BR bridging was 42.1%, with complete response (CR) seen in 17.5%, partial response in 22.5%, and stable disease in 15.0%. Progressive disease was seen in 40% and data were missing for 5%.

"A majority (31 [77.5%] of 40) proceeded to cell infusion; thus, Pola-BR seems to be a feasible bridging strategy. Further studies are required to define who is most likely to benefit from this treatment and to assess other approaches for this chemotherapy-refractory group," noted Northend and fellow researchers.

Sixteen patients treated with CAR T-cell therapy progressed and were treated with Pola-BR. In these patients, ORR was 43.8% and CR was 18.8%. Three patients proceeded to allogeneic SCT and one to autologous after Pola-BR treatment.

Among the 78 patients treated with Pola-BR as stand-alone therapy, 33.3% experienced treatment delay due to adverse events, infection being the most common (17.9%) followed by hematologic toxicity (14.1%). In this group, ORR was 65.8% (CR, 39.7%), median PFS was 5.4 months (95% CI, 3.0-10.8 months), and median OS was 10.2 months (95% CI, 24%-50%) after a median follow-up of 8.2 months. In patients who achieved complete response, median PFS was 14.0 months, and median OS was not reached.

Upon univariate analysis, Northend and colleagues found that factors significantly associated with shorter PFS in this stand-alone treatment group included the following:

  • Refractoriness to last treatment: HR, 3.48; 95% CI, 1.79-6.76; P<0.001.
  • Bulky disease (>7.5 cm): HR, 2.32; 95% CI, 1.23-4.38; P=0.009.
  • More than one previous treatment: HR, 2.17; 95% CI, 1.19-3.95; P=0.01.

"This is the largest data set of patients treated with Pola-BR to date. Other series report broadly similar outcomes, but this study is unique in its sample size and inclusion of patients at different stages in the DLBCL treatment pathway. These outcomes support Pola-BR as a treatment for patients who are ineligible for SCT, help to delineate which groups stand to benefit most, and show efficacy in transformed low-grade lymphoma and double-hit lymphoma which were not represented in the G029365 trial," they wrote.

Disclosures

Northend reported no disclosures.

Sources

Northend M, et al "Results of a United Kingdom real-world study of polatuzumab vedotin, bendamustine, and rituximab for relapsed/refractory DLBCL" Blood Adv 2022; 6(9): 2920-2926.