In a retrospective study reported in the Journal of Clinical Oncology, Schultz et al found poor survival among children and young adults with lack of response to tisagenlecleucel for B-cell acute lymphoblastic leukemia (ALL). Salvage therapy after relapse was capable of inducing responses, but relapse with loss/downregulation of CD19 expression was associated with poor prognosis.
A stated by the investigators, “Nonresponse 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.”
Study Details and Key Findings
The study included 156 patients with complete response and 23 nonresponders from multiple U.S. institutions.
Among the 23 nonresponders, overall survival at 12 months was 19% (95% confidence interval [CI] = 7%–50%). High preinfusion disease burden was present in 22 nonresponders (95%).
Among 156 patients with complete response, relapse had occurred in 57 (37%, 95% CI = 30%–47%) at 12 months. Among 52 patients with available CD19 status at relapse, 22 had CD19 downregulation/loss and 30 had conserved CD19 expression.
Among the 57 patients with relapse, overall survival at 12 months after time of relapse was 52% (95% CI = 38%–71%). A total of 50 patients received salvage therapies after relapse, with the most common first-line salvage therapies consisting of chemotherapy (n = 19), inotuzumab (n = 15), and CD19 CAR T-cell reinfusion. Complete response was achieved in 20 (56%) of 36 evaluable patients with first salvage therapy; when used as initial salvage regimen, inotuzumab produced complete response in 9 (64%) of 14 and CD19 CAR T-cell reinfusion produced complete response in 7 (78%) of 9. However, analysis of efficacy across salvage treatments was limited by high variability in treatment sequencing and responses.
Overall survival at 12 months after relapse was 68% (95% CI = 49%–92%) among patients with conserved CD19 expression at relapse vs 30% (95% CI = 14%–66%) among those with CD19 downregulation/loss at relapse (P = .0068).
The investigators concluded, “We 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.”
Liora M. Schultz, MD, of the Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Stanford Association of Auxiliaries for Children, a St Baldrick’s/Stand Up 2 Cancer Pediatric Dream Team Translational Cancer Research grant, and others. For full disclosures of the study authors, visit ascopubs.org.
