PracticeUpdate Conference Series ASH 2018

Tisagenlecleucel Effectively Treats ALL inUpdate of ELIANATrial Results with this novel CAR T-cell therapy remained robust withmore patients, longer follow-up.

A single infusionwith theCD19+ B-cell eliminating tisagenlecleucel immunotherapy effectively treats pediatric and young adult patients with acute lymphoblastic leukemia (ALL), according to updated results from the phase II ELIANA study. The ELIANA trial enrolled pediatric and young adult patients (≥3 years of age at screening and ≤21 years of age diagnosis) with relapsed/refractory CD19+ B-cell ALL. The median age was 11 years (range 3 years to 24 years). Patients were required to have ≥5% leukemic blasts in bone marrow. As many as 61% of patients had undergone a prior hematopoietic stem cell transplantation. In this follow-up from the original ELIANA trial report, the investigators used data from additional patients and 11 months further follow-up to continue to char- acterize clinical outcomes with tisagenlecleucel. The trial was funded by Novartis, manufacturers of tisagenlecleucel, which is the first chimeric antigen receptor (CAR) T-cell therapy to be approved by the United States FDA for this indication. It func- tions by harnessing T cells to destroy CD19+ B cells implicated in cancer pathogenesis. “Tisagenlecleucel offers a new option for pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia,” said study presenter Stephan A. Grupp, MD, PhD, of the University of Pennsylvania in Philadelphia. After lymphodepleting chemotherapy in most patients (76/79), they received a single infusion of tis- agenlecleucel (median dose 3.0 x 10 6 CAR-positive

viable T cells/kg). Patients were followed for a min- imum of 3 months or until discontinuation (median follow up from infusion = 24 months). With extended follow up, the ELIANA investigators found median overall survival (OS) and median dura- tion of response had not yet been reached (maximum duration of response = 29 months and ongoing). Responses remained ongoing in 29 patients. A total of 19 patients relapsed prior to receiving additional anti-cancer therapy, with 13 subsequent deaths. At 18 months, relapse-free survival was 66% (95% CI 52% to 77%) and OS was 70% (95% CI 58% to 79%). Of the 65 patients who achieved complete response, 64 patients (98%) were major residual disease negative within 3 months. In the abstract, the investigators write that “ELIANA study continues to confirm the efficacy of a single infusion of tisagenlecleucel in pediatric and young adults with ALL without additional therapy.” “The achievement of high overall response rates and deep remissions, in combination with the median duration of response and overall survival not being reached, further corroborate previously reported results,” Grupp and colleagues concluded. Adverse events of grades 3 and 4 did occur in patients who received tisagenlecleucel. As many as 77% of patients experienced cytokine release syndrome, and of these patients, 48% required intensive care unit treatment with a median dura- tion of stay of 7 days. Notably, all observed cases of cytokine release syndrome were medically reversible. Tisagenlecleucel expansion in vivo was correlated with the severity of cytokine release syndrome that patients experienced. Other than cytokine release syndrome, common grade 3/4 adverse events reported in patients receiving tisagenlecleucel included neutropenia with body temperature >38.30C (62% within 8 weeks of infusion), hypoxia (20%) and hypotension (20%). As many as 43% of patients experienced thrombocytopenia, and 54% experienced neutro- penia that was not resolved by day 28. Notably, tisagenlecleucel persisted in some responding patients for 2.5 years or longer, causing B-cell aplasia. However, the majority of adverse events resolved to a grade of 2 or lower by 3-months post-infusion. “Adverse were effec- tively and reproducibly managed,” Dr. Grupp and colleagues concluded. “There were no new safety findings in this longer- term follow-up,” Dr. Grupp said during a press briefing.

Dr. Stephan A. Grupp

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© ASH/Todd Buchanan 2018

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