Abstract
PURPOSENonresponse and relapse after CD19-chimeric antigen receptor (CAR) T-cell therapy continue to challenge survival outcomes. Phase II landmark data from the ELIANA trial demonstrated nonresponse and relapse rates of 14.5% and 28%, respectively, whereas use in the real-world setting showed nonresponse and relapse rates of 15% and 37%. Outcome analyses describing fate after post-CAR nonresponse and relapse remain limited. Here, we aim to establish survival outcomes after nonresponse and both CD19+ and CD19- relapses and explore treatment variables associated with inferior survival.METHODSWe conducted a retrospective multi-institutional study of 80 children and young adults with B-cell acute lymphoblastic leukemia experiencing nonresponse (n = 23) or relapse (n = 57) after tisagenlecleucel. We analyze associations between baseline characteristics and these outcomes and establish survival rates and salvage approaches.RESULTSThe overall survival (OS) at 12 months was 19% across nonresponders (n = 23; 95% CI, 7 to 50). Ninety-five percent of patients with nonresponse had high preinfusion disease burden. Among 156 morphologic responders, the cumulative incidence of relapse was 37% (95% CI, 30 to 47) at 12 months (CD19+; 21% [15 to 29], CD19-; 16% [11 to 24], median follow-up; 380 days). Across 57 patients experiencing relapse, the OS was 52% (95% CI, 38 to 71) at 12 months after time of relapse. Notably, CD19- relapse was associated with significantly decreased OS as compared with patients who relapsed with conserved CD19 expression (CD19- 12-month OS; 30% [14 to 66], CD19+ 12-month OS; 68% [49 to 92], P =.0068). Inotuzumab, CAR reinfusion, and chemotherapy were used as postrelapse salvage therapy with greatest frequency, yet high variability in treatment sequencing and responses limits efficacy analysis across salvage approaches.CONCLUSIONWe describe poor survival across patients experiencing nonresponse to tisagenlecleucel. In the post-tisagenlecleucel relapse setting, patients can be salvaged; however, CD19- relapse is distinctly associated with decreased survival outcomes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 354-363 |
| Number of pages | 10 |
| Journal | Journal of Clinical Oncology |
| Volume | 41 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 10 2023 |
Funding
We acknowledge the following individuals for their major roles in supporting successful execution of this multi-institutional study: administrative support: Anika Dove and Daisy Torres; legal counsel and contracting: Joshua Murphy; and data management: Michelle Fujimoto, Jennifer Sheppard, Jean Sosna, Victoria Koch, Katie Doherty, Emily Bakinowski, Elizabeth Klein, Daritzya Baraja, Courtney Newbold, Glenn McWillians, Maggie Dyer, Kasey Abrahamnson, Angie Peltz, Ahmed Tahoun, Mary Suarez, Megan Hanby, Stacy Cooper, and Brad Muller. The Stanford REDCap platform is developed and operated by Stanford Medicine Research IT team. The REDCap platform services at Stanford are subsidized by 1) Stanford School of Medicine Research Office, and 2) the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant No. UL1 TR001085. Supported by the Stanford Association of Auxiliaries for Children (L.M.S.) and a St Baldrick's/Stand Up 2 Cancer Pediatric Dream Team Translational Cancer Research Grant (C.L.M.). Stand Up 2 Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. C.L.M. is a member of the Parker Institute for Cancer Immunotherapy, which supports the Stanford University Cancer Immunotherapy Program. This work was also supported by the Virginia and D.K. Ludwig Fund for Cancer Research (C.L.M.). K.J.C. acknowledges support of the NIH/NCI Cancer Center Support Grant P30 CA008748.
ASJC Scopus subject areas
- Oncology
- Cancer Research
