According to research published in Blood Advances, tisagenlecleucel following pembrolizumab treatment demonstrated emerging efficacy in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) with high-risk clinical characteristics.

Some researchers have hypothesized that the PD-1 inhibitor pembrolizumab may improve efficacy and cellular expansion of chimeric antigen receptor T-cells (CAR-T).

In the in phase 1b PORTIA study (ClinicalTrials.gov Identifier: NCT03630159), researchers tested this hypothesis in adult patients with R/R DLBCL who received ≥2 prior lines of therapy and had an Eastern Cooperative Oncology Group performance status of ≤1.


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Patients received a tisagenlecleucel infusion on Day 1 and pembrolizumab (200 mg) every 21 days, for up to 6 doses. The patients were separated into 3 cohorts that initiated pembrolizumab on Days 15 (n=4), 8 (n=4), or -1 (n=4).

The study included 15 patients; among those, 3 patients discontinued prior to tisagenlecleucel (2 due to adverse events [AEs] and 1 due to death). Of the remaining 12 patients, 3 patients completed 6 cycles of pembrolizumab (2 who initiated on Day 15 and 1 who initiated on Day –1). The researchers reported that 7 patients discontinued pembrolizumab (5 due to disease progression, 1 due to an AE, and 1 due to patient decision).

Among the 12 patients, there was complete response in 4 (33.3%) patients, partial response in 2 (16.7%) patients, and disease progression in 6 (50.0%) patients. The overall response rate was 50% (95% CI, 21.09-78.91). The researchers found that the cohort initiating pembrolizumab on Day -1 had the highest ORR (75%; 95% CI, 19.41-99.37).

The study was terminated early based on the data analysis and in consideration of other therapies with similar efficacies. “Limited data suggest that the combination of tisagenlecleucel and pembrolizumab was feasible and showed a manageable safety profile, with no DLTs or significant exacerbation of tisagenlecleucel-related AEs,” wrote the investigators. The primary limitations of the study were the small sample size and short follow-up duration.

Disclosure: This research was supported by Novartis Pharmaceuticals Corporation. Please see the original reference for a full list of disclosures.

Reference

Jaeger U, Worel N, McGuirk JP, et al. Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL: results from the phase Ib PORTIA study. Blood Adv. Published online August 31, 2022. doi:10.1182/bloodadvances.2022007779