SCHOLAR-1 (Crump, ASCO 2016) is a large, pooled analysis of rNHL and demonstrated poor outcomes: objective response rate (ORR)= 26%; complete response (CR)=8%. ZUMA-1 is the first, multicenter trial of anti-CD19 CAR T cells (axi-cel) in rNHL and reported positive results: ORR= 82%; CR = 54%. This is a comparative analysis of outcomes from ZUMA-1 and SCHOLAR-1 after adjusting for imbalances in key covariates of patients enrolled.
Eligible pts for both studies had rNHL (stable disease ≤6 mos with ≥4 cycles frontline or ≥ 2 cycles later-line therapy, progressive disease as best response, or relapse ≤12 mos post autologous stem cell transplant). Standardized analyses were performed to account for other baseline covariates that were imbalanced between the studies despite similar inclusion criteria. These analyses equally weighted the proportions of patients with select prognostic covariates between the two studies. The pre-specified covariates selected for weighting were refractory subgroup and occurrence of SCT after refractory status. Sensitivity analyses included additional covariates.
101 ZUMA-1 pts received axi-cel; SCHOLAR-1 included data from 508 pts. Baseline characteristics for each study are listed in the Table. ZUMA-1 median follow-up was 8.7 mos. Using the standardized analysis, the estimated ORR and CR rates in SCHOLAR-1 were 20% and 6%, respectively. Standardized 6-mo survival rate for SCHOLAR-1 was 35%. Risk of death in ZUMA-1 was reduced by 77% relative to SCHOLAR-1 (P < .0001).Table:
|ZUMA-1 mITT||SCHOLAR-1 Response|
|N = 101||N = 508|
|Age, ≥65 y, n (%)||24 (24)||74 (15)|
|Refractory subgroup, n (%)|
|Primary refractory||2 (2)||101 (20)|
|Refractory to ≥ 2L||78 (77)||316 (62)|
Despite the imbalances between the ZUMA-1 and SCHOLAR-1 studies, axi-cel appears to represent a significantly improved treatment option for pts with rNHL compared with currently available therapies as used in the SCHOLAR-1 study.
Clinical trial identification
Legal entity responsible for the study
S.S. Neelapu: Kite research funding, consultant and advisory board member for Kite. F.L. Locke: Scientific advisory board and Moffitt receives research funding from Kite Pharma; Consultant for Cellular Biomedicine Group, Inc. P.M. Reagan: Research Funding: Seattle Genetics. D. Miklos, C.A. Jacobson: Consulting or Advisory Role: PCYC, Sanofi, Adaptive Biotechnologies, Kite, Genentech, Velos; Research Funding: PCYC; Patents: PCYC; Travel Accommodations: PCYC, Sanofi I. Braunschweig: Stock/Equity Ownership: Kite Pharma. T. Siddiqi: Speaker\'s bureau for Pharmacyclics/Jannsen (ibrutinib) and Seattle Genetics (brentuximab vedotin). Y. Lin: Employment: Mayo Clinic; Research funding: Janssen. J. Kuruvilla: Research funding: Celgene, Roche, Karyopharm; consultant: Bristol-Myers Squib, Gilead, Janssen, Hoffman LaRoche, Seattle Genetics; honoraria: Amgen, Bristol-Myers Squibb, Celgene, Gilead, Roche, Janssen, Lundbeck, Merck, Seattle Genetics, B.K. Link, U. Farooq: Research Funding: Kite Pharma. L. Navale, W.Y. Go: Employment: Kite Pharma. J. Wiezorek: Leadership: Kite Pharma. All other authors have declared no conflicts of interest.