A real world study of polatuzumab vedotin, bendamustine, and rituximab (Pola-BR) has backed its efficacy as a treatment for stem cell transplant (SCT)-ineligible patients with with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), as well as its efficacy as a bridging to CAR T-cell therapy.

Researchers from University College London Hospitals (UCL) analysed the efficacy of Pola-BR in 133 patients treated via the Early Access to Medicines Scheme or Cancer Drugs Fund at 28 institutions across the UK.

Polatuzumab was administered on day 1 or 2 of a 28-day cycle at a dose of 1.8mg/kg for a maximum of 6 cycles; dose reduction or a treatment delay due to adverse events was allowed at the discretion of the treating physician.

Treatment intent was bridging to CAR-T for 30.1% (n=40), re-induction therapy with planned SCT consolidation for 9.8% (n=13) and stand-alone treatment (no planned CAR-T/SCT) for 58.6% (n=78). Patients were given a median of 4 cycles of treatment.

The results, published in Blood Advances, showed an objective response rate (ORR) of 57%, with a complete response (CR) in 31.6%. The median follow-up was 7.7 months and median progression-free survival (PFS) and overall survival (OS) were 4.8 months and 8.2 months, respectively.

The ORR for the stand-alone cohort was 65.8% (CR 39.7%), the median follow-up duration was 8.2 months and median PFS and OS were 5.4 months and 10.2 months, respectively.

Of patients achieving CR, median PFS was 14.0 months. Shortened PFS was associated with bulk disease (>7.5cm), more than one prior treatment (hazard ratio [HR] 2.17) and refractoriness to last treatment (HR 3.48), the researchers noted.

One-third of patients (33.3%) in the stand along group experienced treatment delay due to adverse events, the most common of which were found to be infection (17.9%) and haematological toxicity (14.1%). Bendamustine was dose reduced for 42.3% and omitted for 5.1% in at least 1 cycle. Available data showed that 27.1% of patients required hospital admission due to Pola-BR related toxicity during treatment.

The key reasons for treatment discontinuation were found to be completion of 6 cycles (42.3%), PD (32.1%), treatment-related toxicity (17.9%), patient death (2.6%), achieving CR (2.6%), and ‘other’ (2.6%)

Pola-BR was planned as bridging to CAR-T for 40 patients: of these, 77.5% received cell infusion (18 axicabtagene ciloleucel, 12 tisagenlecleucel and 1 clinical trial product), 5 died due to progressive disease (PD), 1 died due to infection, CAR-T infusion was pending for 2 and data were missing for 1.

The best ORR to Pola-BR bridging was 42.1% (CR 17.5%, partial response 22.5%, stable disease 15.0%, PD 40.0%, missing 5.0%). Sixteen patients were given Pola-BR after progressing post-CAR-T; for this cohort the The ORR and CR rate were 43.8% and 18.8%, respectively.

“These outcome data for 133 consecutive patients treated with Pola-BR add substantially to evidence from the registration trial and other studies. Within its limitations (investigator-reported outcomes and limited toxicity data) this retrospective study supports Pola-BR as a treatment for SCT-ineligible patients with R/R DLBCL and provides preliminary evidence of efficacy for CAR-T bridging and after CAR-T failure,” the authors led by Consultant Haematologist Dr Michael Northend concluded.