GLOBAL PIVOTAL PHASE 2 TRIAL OF THE CD19-TARGETED THERAPY CTL019 IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)—AN INTERIM ANALYSIS
Author(s): ,
Stephen J. Schuster
Affiliations:
Lymphoma Program, Abramson Cancer Center,University of Pennsylvania,Philadelphia,United States
,
Michael R. Bishop
Affiliations:
Hematopoietic Cellular Therapy Program,The University of Chicago Medicine,Chicago,United States
,
Constantine Tam
Affiliations:
Division of Hematology and Oncology,Peter MacCallum Cancer Centre,Melbourne,Australia
,
Edmund K. Waller
Affiliations:
Department of Hematology and Medical Oncology,Emory University School of Medicine,Atlanta,United States
,
Peter Borchmann
Affiliations:
Department of Internal Medicine,University Hospital of Cologne,Cologne,Germany
,
Joseph McGuirk
Affiliations:
Department of Blood and Bone Marrow Transplant,The University of Kansas Cancer Center,Kansas City,United States
,
Ulrich Jäger
Affiliations:
Department of Medicine I, Division of Hematology and Hemostaseology,Medical University of Vienna,Vienna,Austria
,
Samantha Jaglowski
Affiliations:
Department of Internal Medicine,The Ohio State University Wexner Medical Center,Columbus,United States
,
Charalambos Andreadis
Affiliations:
Helen Diller Family Comprehensive Cancer Center,University of California San Francisco Medical Center,San Francisco,United States
,
Jason Westin
Affiliations:
Department of Lymphoma/Myeloma,The University of Texas MD Anderson Cancer Center,Houston,United States
,
Isabelle Fleury
Affiliations:
Department of Medicine,University of Montreal, Maisonneuve-Rosemont Hospital CIUSSS East,Montreal,Canada
,
Veronika Bachanova
Affiliations:
Department of Medicine,University of Minnesota,Minneapolis,United States
,
Stephen Ronan Foley
Affiliations:
Department of Medicine,McMaster University,Hamilton,Canada
,
P. Joy Ho
Affiliations:
Institute of Haematology,Royal Prince Alfred Hospital & Sydney University,Sydney,Australia
,
Stephan Mielke
Affiliations:
Medizinische Klinik und Poliklinik II,Universitatsklinikum Würzburg,Würzburg,Germany
,
John M. Magenau
Affiliations:
Department of Internal Medicine Hematology/Oncology,University of Michigan Comprehensive Cancer Center,Ann Arbor,United States
,
Harald Holte
Affiliations:
Department of Oncology,Oslo University Hospital,Oslo,Norway
,
Oezlem Anak
Affiliations:
Global Drug Development,Novartis Pharma AG,Basel,Switzerland
,
Lida Pacaud
Affiliations:
Global Drug Development,Novartis Pharma AG,Basel,Switzerland
,
Rakesh Awasthi
Affiliations:
PK Sciences,Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Feng Tai
Affiliations:
Biostatistics,Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Gilles Salles
Affiliations:
Hospices Civils de Lyon,Université de Lyon,Lyon,France
Richard T. Maziarz
Affiliations:
Center for Hematologic Malignancies, Knight Cancer Institute,Oregon Health & Science University,Portland,United States
(Abstract release date: Jun 8, 2017) EHA Learning Center. Salles G. Jun 25, 2017; 183934
Gilles Salles
Gilles Salles
Login now to access Regular content available to all registered users.

Access to EHA Members only content is an EHA membership benefit.
Click here to join EHA or renew your membership here.


Abstract
Discussion Forum (0)
Rate & Comment (0)

Abstract: LB2604

Type: Late Breaking Oral Session

Presentation during EHA22: On Sunday, June 25, 2017 from 11:15 - 13:30

Location: Hall A

Background
CTL019 is an investigational chimeric antigen receptor (CAR) T-cell therapy with a high rate of durable complete responses (CRs) and a manageable safety profile in a previously reported single-center trial in adult patients (pts) with R/R DLBCL.

Aims
Results of a planned interim analysis of a single-arm, open-label, multicenter, global phase 2 trial of CTL019 in pts ≥ 18 y with R/R DLBCL (JULIET; NCT02445248) are reported.

Methods
Industry-manufactured CAR T cells were provided to pts at 27 centers on 4 continents using a global supply chain. Pts had received ≥ 2 lines of chemotherapy and had disease progression after or were ineligible for autologous stem cell transplant (autoSCT). Autologous T cells were transduced with a lentiviral vector encoding an anti-CD19 CAR, expanded, cryopreserved, shipped, and infused at study sites. The primary endpoint (centrally reviewed by an independent review committee) was best overall response rate (ORR: CR partial response [PR]).

Results
141 pts were enrolled. Following restaging, bridging therapy, and lymphodepleting chemotherapy (fludarabine 25 mg/m2/cyclophosphamide 250 mg/m2/day × 3 days or bendamustine 90 mg/m2/day × 2 days), 85 pts received a single dose of CTL019 transduced cells (median, 3.1 × 108 [range, 0.1-6.0 × 108] cells). Median time from infusion to data cutoff (20 December 2016) was 3.7 mo. Median age was 56 y (range, 24-75) and median prior lines of antineoplastic therapy, 3 (range, 2-7). 51% of pts had prior autoSCT. Among 51 pts with ≥ 3 mo follow-up or earlier discontinuation, best ORR was 59% (95% CI, 44% to 72%) with 43% CR and 16% PR; the primary endpoint was met. CR and PR rates at 3 mo were 37% and 8%, respectively. All pts in CR at 3 mo remained in CR at data cutoff. Efficacy was observed across prognostic subgroups. Median duration of response was not reached. CTL019 was detectable in peripheral blood by quantitative PCR for up to 355 days in responders. Cytokine release syndrome (CRS) was graded using the Penn scale and managed by a protocol-specific algorithm. CRS occurred in 57% of infused pts (17% grade 3; 9% grade 4); no CRS-associated deaths occurred. 16% of pts received tocilizumab for CRS management. 13% of pts had grade 3/4 neurologic adverse events (AEs), managed with supportive care; no cerebral edema was reported. Grade 3/4 cytopenias lasting > 28 days and grade 3/4 febrile neutropenia occurred in 21% and 14% of pts, respectively. 3 pts died from disease progression within 30 days of infusion. No deaths were attributed to CTL019.

Conclusion
This planned interim analysis of a global study of CTL019 in adults with R/R DLBCL confirms the high response rates and durable CRs observed in the previous single-center experience in a cohort of highly pretreated patients. Centralized manufacturing was feasible. CTL019 was generally tolerated without instance of treatment-related mortality. CRS and other AEs could be effectively and reproducibly managed by appropriately trained investigators.

Session topic: 20. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): CD19, Diffuse large B cell lymphoma, T cell

Code of conduct/disclaimer available in General Terms & Conditions