Polatuzumab- Rituximab with or without Bendamustine As Second-Line Therapy for Relapsed Refractory Large B-Cell Lymphomas: Single Center Experience

Introduction: Polatuzumab-vedotin, a CD79 antibody drug conjugate, is approved in combination with bendamustine and rituximab (Pola-BR) in patients with relapsed or refractory (R/R) Large B-cell Lymphoma (LBCL) who have received at least 2 prior lines of therapy. However, the registrational phase Ib/II study by Dr. Sehn and colleagues (Sehn et al. J Clin Oncol 2019) included 11 patients treated with this regimen as second line (2L) therapy. Given these data, real world applications have included the use of 2L polatuzumab rituximab (Pola-R) combination, with or without bendamustine, either as stand-alone treatment or as a bridge to cellular therapy. Here, we sought to analyze institutional outcomes of LBCL patients treated with this regimen and to determine whether the pattern of failure to frontline chemoimmunotherapy (1L CIT) was associated with subsequent response to polatuzumab containing regimen.

Methods: We retrospectively reviewed data on 22 patients who received Pola-R with or without bendamustine as 2L therapy for LBCL at Miami Cancer Institute as of January 31^st, 2022. Response was assessed by investigators using the Lugano criteria (Cheson et al. J Clin Oncol 2014). Objective response rate (ORR) and complete response (CR) rates were compared between primary refractory (no CR to 1L CIT) and relapsed LBCL patients. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.

Results: Baseline characteristics are summarized in Table 1. The median age was 73 years (range, 57 to 92). Seven (32%) patients were ≥80 years old. The majority of patients (54%) had de novo DLBCL and non-GCB (59%) cell of origin by Hans algorithm. The median number of polatuzumab cycles was 4 (range, 1 to 7 cycles). Pola-BR was initiated with full dose bendamustine for 14 (64%) patients. Bendamustine was omitted for 6 (27%) patients and 2 (9%) patients received both Pola-R and Pola-BR cycles. The investigator-assessed best ORR was 68% (95% confidence interval [CI], 48.7% to 87.6%). Fourteen (64%) patients achieved a CR. Of the 6 patients who received Pola-R, 67% achieved a CR. The ORR was 90% for patients with relapsed disease, and 40% for those with primary refractory disease (p=0.057). CR rates were significantly lower in patients with disease refractory to 1L CIT (p=0.019). Median follow-up was 11 months. Nine (41%) patients received cellular therapy after polatuzumab containing regimen. Of these, 4 patients received CD19 targeted CAR T-cell therapy, and 5 patients received high dose chemotherapy followed by autologous stem cell transplant (ASCT). Other subsequent therapies after polatuzumab were: tafasitamab plus lenalidomide (n=1), loncastuximab tesirine (n=1) and conventional salvage CIT (n=3). Median PFS and OS were not reached. The 1-year PFS and OS were 54.5% (95% CI, 32.1% to 76.9%) and 70.5% (95% CI, 47.6% to 93.4%), respectively. Progression free survival and overall survival estimates are shown in Figure 1.

Conclusions: Polatuzumab-Rituximab with or without bendamustine is an effective salvage option for R/R LBCL patients in the second-line setting. Refractoriness to frontline CIT was associated with lower response to subsequent polatuzumab treatment. Patients treated with this regimen can be successfully bridged to cellular approaches as definitive therapy.

Nahas:Gilead: Honoraria; Janssen: Speakers Bureau; GSK: Honoraria; Blueprint: Speakers Bureau; BMS: Speakers Bureau; GSK: Honoraria; BLUEPRINT: Speakers Bureau. Feinstein:Amgen: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Ahluwalia:Elekta, Inc.: Consultancy; Bayer HealthCare Pharmaceuticals Inc.: Consultancy; Celularity Inc.: Consultancy; Servier Pharmaceuticals LLC: Consultancy; GlaxoSmithKline, LLC.: Consultancy; VIEWRAY TECHNOLOGIES INC: Consultancy; Janssen Global Services, LLC: Consultancy; InSightec,Inc: Consultancy. Linhares:Jazz Pharmaceuticals: Consultancy; Seagen: Consultancy, Research Funding; Celgene: Consultancy; Kyowa Kirin: Consultancy, Speakers Bureau; TG Therapeutics: Consultancy; GlaxoSmithKline: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Gilead: Consultancy; BeiGene: Consultancy, Research Funding; Novartis: Consultancy; BMS: Consultancy, Research Funding; Morphosis: Consultancy, Research Funding; Gilead: Consultancy.

Polatuzumab is a CD79b-directed antibody-drug conjugate indicated in combination with bendamustine and a rituximab product for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, after at least two prior therapies. In our retrospective real world study polatuzumab was administered after 1 prior therapy and was administered without bendamustine in some patients.