EHA Library - The official digital education library of European Hematology Association (EHA)

SAFETY AND EFFICACY OF TISAGENLECLEUCEL PLUS PEMBROLIZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: UPDATED ANALYSIS OF THE PHASE 1B PORTIA STUDY
Author(s): ,
Ulrich Jaeger
Affiliations:
Medical University of Vienna,Vienna,Austria
,
Nina Worel
Affiliations:
Medical University of Vienna,Vienna,Austria
,
Joseph McGuirk
Affiliations:
University of Kansas Medical Center,Kansas City,United States
,
Peter Riedell
Affiliations:
University of Chicago,Chicago,United States
,
Isabelle Fleury
Affiliations:
Maisonneuve-Rosemont Hospital, University of Montreal,Montreal,Canada
,
Peter Borchmann
Affiliations:
University Hospital Cologne,Cologne,Germany
,
Yan Du
Affiliations:
Novartis Pharma AG,Shanghai,China
,
Ahmed Abdelhady
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Xia Han
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Marcela Martinez-Prieto
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
Edmund Waller
Affiliations:
Emory University Winship Cancer Institute,Atlanta,United States
EHA Library. Jaeger U. 06/09/21; 325276; EP516
Prof. Dr. Ulrich Jaeger
Prof. Dr. Ulrich Jaeger
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

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

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

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

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