EFFICACY AND SAFETY OF TISAGENLECLEUCEL IN ADULT PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA: PRIMARY ANALYSIS OF THE PHASE 2 ELARA TRIAL
Author(s): ,
Stephen J Schuster
Affiliations:
University of Pennsylvania,Philadelphia, PA,United States
,
Michael Dickinson
Affiliations:
Peter MacCallum Cancer Centre and Royal Melbourne Hospital,Melbourne,Australia
,
Martin Dreyling
Affiliations:
Medizinische Klinik III,LMU Klinikum,Munich,Germany
,
Joaquin Martinez-Lopez
Affiliations:
Hospital 12 De Octubre,Complutense University,CNIO, Madrid,Spain
,
Arne Kolstad
Affiliations:
Oslo University Hospital,Oslo,Norway
,
Jason Butler
Affiliations:
Royal Brisbane Hospital,Herston,Australia
,
Monalisa Ghosh
Affiliations:
Michigan Medicine University of Michigan,Ann Arbor, MI,United States
,
Leslie Popplewell
Affiliations:
City of Hope National Medical Center,Duarte, CA,United States
,
Julio C. Chavez
Affiliations:
Moffitt Cancer Center,Tampa, FL,United States
,
Emmanuel Bachy
Affiliations:
Hospices Civils de Lyon and Université Claude Bernard Lyon 1,Lyon,France
,
Koji Kato
Affiliations:
Kyushu University Hospital,Fukuoka,Japan
,
Hideo Harigae
Affiliations:
Tohoku University Hospital,Sendai,Japan
,
Marie José Kersten
Affiliations:
Cancer Center Amsterdam,Amsterdam UMC, University of Amsterdam,Amsterdam,Netherlands
,
Charalambos Andreadis
Affiliations:
Helen Diller Family Comprehensive Cancer Center,University of California San Francisco,San Francisco, CA,United States
,
Peter A. Riedell
Affiliations:
University of Chicago,Chicago, IL,United States
,
Ahmed Abdelhady
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover, NJ,United States
,
Aiesha Zia
Affiliations:
Novartis Pharma AG,Basel,Switzerland
,
Mony Chenda Morisse
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover, NJ,United States
,
Nathan Hale Fowler
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston, TX,United States;BostonGene,Waltham, MA,United States
Catherine Thieblemont
Affiliations:
APHP,Hôpital Saint-Louis-Université de Paris,Paris,France
EHA Library. Dreyling M. 06/09/21; 324618; S210
Dr. Martin Dreyling
Dr. Martin Dreyling
Contributions
Abstract
Presentation during EHA2021: All Oral 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.

This abstract is embargoed until Saturday, June 12, 09:00 CEST

Abstract: S210

Type: Oral Presentation

Session title: Indolent & mantle cell lymphoma - Clinical

Background
Most patients with relapsed/refractory follicular lymphoma (r/r FL) experience multiple relapses and progressively worse clinical outcomes with each line of therapy, underlining a need for novel therapies. Tisagenlecleucel has demonstrated durable responses and manageable safety in adult patients with r/r diffuse large B-cell lymphoma.

Aims
To report the primary analysis of ELARA (NCT03568461), an international, single-arm phase 2 trial of tisagenlecleucel in adult patients with r/r FL.

Methods
Eligible patients (≥18 years) had r/r FL (grades 1-3A) after ≥2 lines of therapy or had failed autologous stem cell transplant. Bridging therapy was permitted followed by disease assessment prior to tisagenlecleucel infusion. Patients received tisagenlecleucel (0.6-6×108 CAR+ viable T cells) after lymphodepleting chemotherapy. The primary endpoint was complete response rate (CRR) by central review per Lugano 2014 criteria. Secondary endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival, safety, and cellular kinetics. Predefined primary analysis occurred when ≥90 treated patients had ≥6 months of follow-up. 

Results
As of September 28, 2020, 98 patients were enrolled and 97 received tisagenlecleucel (median follow-up, 10.6 months). At study entry, median age among treated patients was 57 years (range, 29-73), 85% had stage III-IV disease, 60% had a FLIPI score ≥3, 65% had bulky disease, and 42% had LDH greater than the upper limit of normal. The median number of prior therapies was 4 (range, 2-13); 78% of patients were refractory to their last treatment (76% to any ≥2 prior regimens) and 60% progressed within 2 years of initial anti-CD20-containing treatment. Of 94 patients evaluable for efficacy, the CRR was 66% (95% CI, 56-75) and the ORR was 86% (95% CI, 78-92). CRRs/ORRs were comparable among key high-risk subgroups. Estimated DOR (CR) and PFS rates at 6 month were 94% (95% CI, 82-98) and 76% (95% CI, 65-84), respectively. Of 97 patients evaluable for safety, 65% experienced grade ≥3 adverse events within 8 weeks post-infusion, most commonly neutropenia (28%) and anemia (13%). Any-grade cytokine release syndrome (per Lee scale) occurred in 49% of patients (grade ≥3, 0%). Any-grade neurological events (per CTCAE v4.03) occurred in 9% of patients (grade 3, 0%; grade 4, 1 patient and recovered). Three patients died from progressive disease.

Cellular kinetic parameters for tisagenlecleucel were estimated using transgene levels (by qPCR) in peripheral blood. Median maximal expansion (Cmax) and exposure during the first 28 days following infusion (AUC0-28d) were similar between responders (CR or partial response) and non-responders (stable or progressive disease). Maximum transgene levels were reached by a median of 10 days in responders and 12.9 days in non-responders; transgene persistence was detected up to 370 days and 187 days, respectively. 

Conclusion
These data demonstrate the efficacy and acceptable safety of tisagenlecleucel in patients with r/r FL, including high-risk patients after multiple lines of prior therapy, and suggest that tisagenlecleucel may be a promising therapy for patients with r/r FL. 

Keyword(s): CAR-T, Clinical outcome, Follicular lymphoma, Phase II

Presentation during EHA2021: All Oral 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.

This abstract is embargoed until Saturday, June 12, 09:00 CEST

Abstract: S210

Type: Oral Presentation

Session title: Indolent & mantle cell lymphoma - Clinical

Background
Most patients with relapsed/refractory follicular lymphoma (r/r FL) experience multiple relapses and progressively worse clinical outcomes with each line of therapy, underlining a need for novel therapies. Tisagenlecleucel has demonstrated durable responses and manageable safety in adult patients with r/r diffuse large B-cell lymphoma.

Aims
To report the primary analysis of ELARA (NCT03568461), an international, single-arm phase 2 trial of tisagenlecleucel in adult patients with r/r FL.

Methods
Eligible patients (≥18 years) had r/r FL (grades 1-3A) after ≥2 lines of therapy or had failed autologous stem cell transplant. Bridging therapy was permitted followed by disease assessment prior to tisagenlecleucel infusion. Patients received tisagenlecleucel (0.6-6×108 CAR+ viable T cells) after lymphodepleting chemotherapy. The primary endpoint was complete response rate (CRR) by central review per Lugano 2014 criteria. Secondary endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival, safety, and cellular kinetics. Predefined primary analysis occurred when ≥90 treated patients had ≥6 months of follow-up. 

Results
As of September 28, 2020, 98 patients were enrolled and 97 received tisagenlecleucel (median follow-up, 10.6 months). At study entry, median age among treated patients was 57 years (range, 29-73), 85% had stage III-IV disease, 60% had a FLIPI score ≥3, 65% had bulky disease, and 42% had LDH greater than the upper limit of normal. The median number of prior therapies was 4 (range, 2-13); 78% of patients were refractory to their last treatment (76% to any ≥2 prior regimens) and 60% progressed within 2 years of initial anti-CD20-containing treatment. Of 94 patients evaluable for efficacy, the CRR was 66% (95% CI, 56-75) and the ORR was 86% (95% CI, 78-92). CRRs/ORRs were comparable among key high-risk subgroups. Estimated DOR (CR) and PFS rates at 6 month were 94% (95% CI, 82-98) and 76% (95% CI, 65-84), respectively. Of 97 patients evaluable for safety, 65% experienced grade ≥3 adverse events within 8 weeks post-infusion, most commonly neutropenia (28%) and anemia (13%). Any-grade cytokine release syndrome (per Lee scale) occurred in 49% of patients (grade ≥3, 0%). Any-grade neurological events (per CTCAE v4.03) occurred in 9% of patients (grade 3, 0%; grade 4, 1 patient and recovered). Three patients died from progressive disease.

Cellular kinetic parameters for tisagenlecleucel were estimated using transgene levels (by qPCR) in peripheral blood. Median maximal expansion (Cmax) and exposure during the first 28 days following infusion (AUC0-28d) were similar between responders (CR or partial response) and non-responders (stable or progressive disease). Maximum transgene levels were reached by a median of 10 days in responders and 12.9 days in non-responders; transgene persistence was detected up to 370 days and 187 days, respectively. 

Conclusion
These data demonstrate the efficacy and acceptable safety of tisagenlecleucel in patients with r/r FL, including high-risk patients after multiple lines of prior therapy, and suggest that tisagenlecleucel may be a promising therapy for patients with r/r FL. 

Keyword(s): CAR-T, Clinical outcome, Follicular lymphoma, Phase II

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