AN UPDATED ANALYSIS OF JULIET, A GLOBAL PIVOTAL PHASE 2 TRIAL OF TISAGENLECLEUCEL IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)
Author(s): ,
Peter Borchmann
Affiliations:
Department of Haematology and Oncology,University Hospital of Cologne,Cologne,Germany
,
Constantine S. Tam
Affiliations:
Peter MacCallum Cancer Centre, St Vincent’s Hospital and University of Melbourne,Melbourne,Australia
,
Ulrich Jäger
Affiliations:
Dept. of Medicine I, Div. of Hematology and Hemostaseology,Medical University of Vienna,Vienna,Austria
,
Joseph P. McGuirk
Affiliations:
Department of Blood and Bone Marrow Transplant,The University of Kansas Medical Center,Kansas City,United States
,
Harald Holte
Affiliations:
Department of Oncology,Oslo University Hospital,Oslo,Norway
,
Edmund K. Waller
Affiliations:
Winship Cancer Institute of Emory University, Bone Marrow and Stem Cell Transplant Center,Atlanta,United States
,
Samantha M. Jaglowski
Affiliations:
The James Cancer Hospital and Solove Research Institute, The Ohio State University Comprehensive Cancer Center,Columbus,United States
,
Michael R. Bishop
Affiliations:
University of Chicago, Hematopoietic Stem Cell Transplantation Program,Chicago,United States
,
Charalambos Andreadis
Affiliations:
Department of Hematology and Blood and Marrow Transplant,University of California San Francisco Helen Diller Family Comprehensive Cancer Center,San Francisco,United States
,
Stephen Ronan Foley
Affiliations:
Juravinski Hospital and Cancer Centre, McMaster University,Hamilton,Canada
,
Jason R. Westin
Affiliations:
Department of Lymphoma and Myeloma, Division of Cancer Medicine,The University of Texas M.D. Anderson Cancer Center,Houston,United States
,
Isabelle Fleury
Affiliations:
Maisonneuve-Rosemont Hospital, University of Montreal,Montreal,Canada
,
P. Joy Ho
Affiliations:
Royal Prince Alfred Hospital and Department of Medicine,The University of Sydney,Sydney,Australia
,
Stephan Mielke
Affiliations:
Würzburg University Medical Center, Center for Allogeneic Stem Cell Transplantation,Würzburg,Germany
,
Gilles Salles
Affiliations:
Department of Hematology,Hospices Civils de Lyon, Université de Lyon,Lyon,France
,
Richard T. Maziarz
Affiliations:
Oregon Health & Science Knight Cancer Institute, Center for Hematologic Malignancies,Portland,United States
,
Özlem Anak
Affiliations:
Novartis Pharma AG,Basel,Switzerland
,
Lida Bubuteishvili Pacaud
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Christopher del Corral
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Rakesh Awasthi
Affiliations:
Novartis Institutes for BioMedical Research,East Hanover,United States
,
Sergei Agoulnik
Affiliations:
Novartis Precision Medicine,Cambridge,United States
,
Feng Tai
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
Stephen J. Schuster
Affiliations:
Lymphoma Program, Abramson Cancer Center University of Pennsylvania,Philadelphia,United States
EHA Learning Center. Borchmann P. Jun 16, 2018; 214521
Peter Borchmann
Peter Borchmann

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Abstract: S799

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 11:30 - 11:45

Location: Room A1

Background
Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy with a high rate of durable complete responses and a manageable safety profile in adult patients (pts) with R/R DLBCL.

Aims
To report long-term follow up of safety and efficacy in a single-arm, open-label, global phase 2 trial of tisagenlecleucel in pts ≥18 y with R/R DLBCL (JULIET; NCT02445248).

Methods
Eligible pts had r/r DLBCL, received ≥2 lines of therapy, including rituximab and anthracycline, and were ineligible for/failed autologous stem cell transplant (ASCT). Centrally manufactured CAR T cells were provided using cryopreserved apheresis and a global supply chain. The primary endpoint was best ORR (CR + PR) per independent review committee. Efficacy results are reported for pts in the main cohort with ≥3 mo follow-up or earlier discontinuation; safety is reported for all infused pts.

Results
At data cutoff (8 Dec 2017), 165 pts were enrolled and 111 infused (95 with US-manufactured [main cohort] and 16 with EU-manufactured [cohort A] tisagenlecleucel) with a single dose of tisagenlecleucel (median, 3.0×108 [range, 0.1-6.0×108] cells). 92% of pts received bridging therapy and 93% received lymphodepleting chemotherapy. Median time from infusion to data cutoff, 13.9 mo. Median age, 56 y (range, 22-76; 23% >65 y). At study entry, 76% of infused pts had stage III/IV disease, 17% had double/triple hits in MYC/BCL2/BCL6. 57% had germinal center B-cell; 41% had activated B-cell molecular subtypes. Median number of prior lines of antineoplastic therapy, 3 (range, 1-6; 95% had ≥2); 49% had prior ASCT. 93 pts had ≥3 mo and 81 pts had ≥12 mo of follow-up or discontinued earlier and were evaluable for efficacy. Best ORR was 52% (95% CI, 41-62) with 40% CR and 12% PR. Response rates were consistent across prognostic subgroups (including prior ASCT and double-hit lymphoma). Median duration of response was not reached; the 12-mo probability of being relapse-free was 65% (95% CI, 49-78; max follow-up, 17.3 mo). Median OS among all infused pts was 11.7 mo (95% CI, 6.6-NE); OS probability at mo 12, 49% (95% CI, 38.5-59). No pts proceeded to allo/ASCT while in remission. Tisagenlecleucel was detected in peripheral blood by qPCR for ≤693 days in responders. Grade (G)3 or 4 AEs of special interest ≤8 weeks of infusion included cytokine release syndrome (CRS; 14% G3 and 8% G4 by the Penn grading scale and managed by a protocol-specific algorithm), neurologic AEs (12%, managed with supportive care; no cases of cerebral edema were observed), cytopenias lasting >28 days (32%), infections (20%), and febrile neutropenia (14%). 15% received tocilizumab for CRS management. 3 pts died ≤30 days of infusion (all disease progression). No deaths were attributed to tisagenlecleucel or CRS. Since previous reports, no new deaths occurred due to causes other than disease progression. Analyses to better characterize and predict severe CRS, including relationships with baseline clinical/laboratory parameters, cytokines, dose, cellular kinetics and neurologic events will be presented.

Conclusion
Tisagenlecleucel produces high response rates in a cohort of highly pretreated adult pts with r/r DLBCL. With longer follow-up, these results confirm findings of an earlier primary analysis and show prolonged durable responses can be achieved. Centralized manufacturing was feasible in the first global study of CAR T cell therapy in DLBCL. CRS and other AEs could be effectively and reproducibly managed by appropriately trained investigators without treatment-related mortality.

Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Diffuse large B cell lymphoma, Targeted therapy

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