Contributions
Abstract: EP516
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Tisagenlecleucel showed durable responses and manageable safety in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) in the phase 2 JULIET trial. High baseline programmed cell death 1 (PD-1) expression associated with higher probability of no response (Schuster et al. NEJM 2019).
Aims
To report an updated analysis of PORTIA, a phase 1b, multicenter, open-label study of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL.
Methods
Eligible patients (≥18 year) had r/r DLBCL after ≥2 lines of therapy and relapsed after or were not candidates for autologous stem cell transplant (autoSCT). Patients received a single tisagenlecleucel infusion on Day 1 and were enrolled in 1 of 3 cohorts that initiated pembrolizumab (200 mg q 21 days, for up to 6 doses) on either Days +15, +8, or –1. Primary endpoints were incidence of dose-limiting toxicities (DLTs) and overall response rate (ORR; complete response [CR] and partial response [PR]). Secondary endpoints included duration of response, progression-free survival, overall survival, safety, and cellular kinetics.
Results
As of November 9, 2020, 15 patients were enrolled and 12 received tisagenlecleucel (n=4 patients for each Days +15, +8, and –1 cohorts; median follow-up, 4 mo). At study entry, the median age among treated patients was 62 year (range, 35-79), 100% had an International Prognostic Index score ≥2, 67% had ≥3 prior lines of therapy, 58% had stage IV disease, 58% had lactate dehydrogenase greater than upper limit of normal, and 42% had prior autoSCT. All 12 patients had ≥1 adverse events (AE). Grade ≥3 AEs suspected to be related to tisagenlecleucel and/or pembrolizumab were neutropenia (n=4); neutrophil count decreased (n=3); febrile neutropenia, lymphocyte count decreased, malnutrition (each n=2); anemia, leukopenia, diarrhea, white blood count decreased, liver function tests increased, thrombocytopenia, hepatitis, and cytokine release syndrome (CRS; each n=1). No neurotoxicity or DLTs were observed. Among the Day +15, +8, and –1 cohorts (each n=4), the ORR was 50% (2/4; CR n=0, PR n=2), 25% (1/4; CR n=1, PR n=0), and 25% (1/4; CR n=1, PR n=0; longer follow-up is needed for n=2 patients), respectively. Tisagenlecleucel exposure and peak expansion were consistent with JULIET, with a trend toward delayed expansion in the Day –1 cohort (n=4). There was no sign of secondary expansion following pembrolizumab administration regardless of the number of doses. Compared with JULIET, lower CRS severity and frequency and lower cytokine profiles were observed for all 3 cohorts.
Conclusion
The combination of tisagenlecleucel plus pembrolizumab was feasible and showed manageable safety. The lack of improved efficacy in PORTIA with the addition of pembrolizumab compared with tisagenlecleucel alone may be related to more patients with ≥3 prior lines of therapy (67% vs 51%, respectively), and/or patients with more advanced disease in PORTIA. Additional studies with larger patient cohorts are needed to determine the value of adding PD-1 inhibitors to CAR-T cell therapy in patients with r/r DLBCL.
Clinical trial information: NCT03630159
Keyword(s): Diffuse large B cell lymphoma, Non-Hodgkin's lymphoma, Relapsed lymphoma
Abstract: EP516
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Tisagenlecleucel showed durable responses and manageable safety in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) in the phase 2 JULIET trial. High baseline programmed cell death 1 (PD-1) expression associated with higher probability of no response (Schuster et al. NEJM 2019).
Aims
To report an updated analysis of PORTIA, a phase 1b, multicenter, open-label study of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL.
Methods
Eligible patients (≥18 year) had r/r DLBCL after ≥2 lines of therapy and relapsed after or were not candidates for autologous stem cell transplant (autoSCT). Patients received a single tisagenlecleucel infusion on Day 1 and were enrolled in 1 of 3 cohorts that initiated pembrolizumab (200 mg q 21 days, for up to 6 doses) on either Days +15, +8, or –1. Primary endpoints were incidence of dose-limiting toxicities (DLTs) and overall response rate (ORR; complete response [CR] and partial response [PR]). Secondary endpoints included duration of response, progression-free survival, overall survival, safety, and cellular kinetics.
Results
As of November 9, 2020, 15 patients were enrolled and 12 received tisagenlecleucel (n=4 patients for each Days +15, +8, and –1 cohorts; median follow-up, 4 mo). At study entry, the median age among treated patients was 62 year (range, 35-79), 100% had an International Prognostic Index score ≥2, 67% had ≥3 prior lines of therapy, 58% had stage IV disease, 58% had lactate dehydrogenase greater than upper limit of normal, and 42% had prior autoSCT. All 12 patients had ≥1 adverse events (AE). Grade ≥3 AEs suspected to be related to tisagenlecleucel and/or pembrolizumab were neutropenia (n=4); neutrophil count decreased (n=3); febrile neutropenia, lymphocyte count decreased, malnutrition (each n=2); anemia, leukopenia, diarrhea, white blood count decreased, liver function tests increased, thrombocytopenia, hepatitis, and cytokine release syndrome (CRS; each n=1). No neurotoxicity or DLTs were observed. Among the Day +15, +8, and –1 cohorts (each n=4), the ORR was 50% (2/4; CR n=0, PR n=2), 25% (1/4; CR n=1, PR n=0), and 25% (1/4; CR n=1, PR n=0; longer follow-up is needed for n=2 patients), respectively. Tisagenlecleucel exposure and peak expansion were consistent with JULIET, with a trend toward delayed expansion in the Day –1 cohort (n=4). There was no sign of secondary expansion following pembrolizumab administration regardless of the number of doses. Compared with JULIET, lower CRS severity and frequency and lower cytokine profiles were observed for all 3 cohorts.
Conclusion
The combination of tisagenlecleucel plus pembrolizumab was feasible and showed manageable safety. The lack of improved efficacy in PORTIA with the addition of pembrolizumab compared with tisagenlecleucel alone may be related to more patients with ≥3 prior lines of therapy (67% vs 51%, respectively), and/or patients with more advanced disease in PORTIA. Additional studies with larger patient cohorts are needed to determine the value of adding PD-1 inhibitors to CAR-T cell therapy in patients with r/r DLBCL.
Clinical trial information: NCT03630159
Keyword(s): Diffuse large B cell lymphoma, Non-Hodgkin's lymphoma, Relapsed lymphoma