CLINICAL AND BIOLOGIC COVARIATES OF OUTCOMES IN ZUMA-1: A PIVOTAL TRIAL OF AXICABTAGENE CILOLEUCEL (AXI-CEL; KTE-C19) IN PATIENTS WITH REFRACTORY AGGRESSIVE NON-HODGKIN LYMPHOMA (NHL)
Author(s): ,
Frederick L. Locke
Affiliations:
H Lee Moffitt Cancer Center & Research Institute,Tampa,United States
,
Sattva S. Neelapu
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Nancy L. Bartlett
Affiliations:
Washington University,St. Louis,United States
,
Lazaros J. Lekakis
Affiliations:
University of Miami,Miami,United States
,
David Miklos
Affiliations:
Stanford University,Stanford,United States
,
Caron A. Jacobson
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Ira Braunschweig
Affiliations:
Montefiore Medical Center,Bronx,United States
,
Olalekan Oluwole
Affiliations:
Vanderbilt University Medical Center,Nashville,United States
,
Tanya Siddiqi
Affiliations:
City of Hope,Duarte,United States
,
Yi Lin
Affiliations:
Mayo Clinic,Rochester,United States
,
John Timmerman
Affiliations:
University of California at Los Angeles,Los Angeles,United States
,
Patrick M. Reagan
Affiliations:
University of Rochester School of Medicine,Rochester,United States
,
Adrian Bot
Affiliations:
Kite Pharma,Santa Monica,United States
,
John Rossi
Affiliations:
Kite Pharma,Santa Monica,United States
,
Lynn Navale
Affiliations:
Kite Pharma,Santa Monica,United States
,
Yizhou Jiang
Affiliations:
Kite Pharma,Santa Monica,United States
,
Jeff Aycock
Affiliations:
Kite Pharma,Santa Monica,United States
,
Meg Elias
Affiliations:
Kite Pharma,Santa Monica,United States
,
Jeff Wiezorek
Affiliations:
Kite Pharma,Santa Monica,United States
William Y. Go
Affiliations:
Kite Pharma,Santa Monica,United States
(Abstract release date: May 18, 2017) EHA Learning Center. Lin Y. Jun 24, 2017; 181753

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Abstract
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Abstract: S466

Type: Oral Presentation

Presentation during EHA22: On Saturday, June 24, 2017 from 16:00 - 16:15

Location: Hall C

Background
Outcomes for pts with refractory aggressive NHL are poor with current therapies (Crump, ASCO 2016). Results from the interim analysis of (n=62) of ZUMA-1, the 1st multicenter trial of an anti-CD19 chimeric antigen receptor (CAR) T cell, axi-cel, in refractory aggressive NHL, showed an objective response rate (ORR) of 79% (complete response [CR] 52%; Blood 2016;128:LBA-6). Here we present results from the primary analysis of ZUMA-1.

Aims
Here we present results from the primary analysis of the ZUMA-1 trial. 

Methods
Pts received a target dose of 2 × 106 anti-CD19 CAR T cells/kg after low- dose conditioning with cyclophosphamide and fludarabine. Eligible pts (≥18 y) had diffuse large B cell lymphoma (DLBCL), primary mediastinal B cell lymphoma (PMBCL) or transformed follicular lymphoma (TFL); an ECOG performance status (PS) 0-1; and refractory disease (progressive or stable disease as best response to last prior therapy, or relapsed ≤12 m of autologous stem cell transplant [ASCT]). The primary endpoint for this analysis was ORR in the combined DLBCL, PMBCL, and TFL population. Key secondary endpoints were duration of response (DOR), overall survival (OS), and frequency of adverse events (AEs). The primary analysis was triggered when 92 pts had at least 6 m of follow-up

Results
As of January 27, 2017, 111 pts from 22 institutions were enrolled; 101 pts (91%) received axi-cel. Median age was 58 y (range, 23-76), 67% male, 85% stage III-IV, 47% IPI 3-4, 77% refractory to ≥2nd line of therapy, and 21% relapsed ≤12 m of ASCT. Axi-cel was successfully manufactured in 110/111 (99%) pts with an average turnaround time from apheresis to the clinical site of 17 d.

With an ORR of 82% (n = 92; P<.0001) the study met the primary endpoint. The ORR in the mITT analysis set of 101 pts was 82% (CR 54%, PR 28%), and was consistent across key covariates including disease subtype, refractory status, stage, and IPI score.  At a median follow up of 8.7 m, 44% of pts were in response and 39% were in CR. The median DOR was 8.2 m overall and not reached for pts who achieved a CR. Median OS was not reached; 80% of pts remained alive at 6 m. The most common Gr ≥3 treatment-emergent AEs were neutropenia (66%), leukopenia (44%), anemia (43%), febrile neutropenia (31%), and encephalopathy (21%). Gr ≥3 cytokine release syndrome (CRS) and neurologic events (NE) occurred in 13% and 28% of pts, respectively. All CRS and all NE resolved except 1 Gr 1 memory impairment. As previously reported, there were 3 Gr 5 AEs (3%). Peak CAR T levels and AUC post–axi-cel were associated with durable responses. Additionally, this presentation will include an expanded analysis of efficacy outcomes by novel biologic and clinical covariates including key molecular phenotypes and tocilizumab/corticosteroid interventions used for management of adverse events.

Conclusion
Axi-cel significantly improved ORR in patients with refractory aggressive NHL. The CR rate was 7-fold higher compared to historical controls (Crump, ASCO 2016) and nearly half the patients had an ongoing response. Axi-cel demonstrated significant clinical benefit with a manageable safety profile in pts lacking curative treatment options.

Drs Locke and Neelapu contributed equally to this study

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

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