Higher doses of tisagenlecleucel are associated with improved outcomes: a report from the pediatric real-world CAR consortium

• Authors: Heather E Stefanski, University of Minnesota, Minneapolis; Anne Eaton, University of Minnesota, Minneapolis; Christina Baggott, Stanford University; Jenna Rossoff, Ann & Robert H Lurie Childrens Hosp Chicago; Michael R Verneris, University of Colorado, Aurora; Snehit Prabhu, Stanford University; Holly L Pacenta, University of Texas Southwestern Medical Center/Children’s Health, Dallas; Christine L Phillips, University of Cincinnati; Julie-An Talano, Medical College of Wisconsin and Children’s Wisconsin, Milwaukee; Amy Moskop, Medical College of Wisconsin and Children’s Wisconsin, Milwaukee; Steven P Margossian, Harvard Medical School; Gary Douglas Myers, University of Missouri Kansas City; Nicole A Karras, City of Hope National Medical Center; Patrick A Brown, John Hopkins School of Medicine; Muna Qayed, Emory University; Michelle Hermiston, University of California San Francisco; Prakash Satwani, Columbia University; Christa M Krupski, University of Cincinnati; Amy K Keating, University of Colorado, Aurora; Rachel Wilcox, University of Missouri Kansas City; Cara A Rabik, US Food and Drug Administration, Silver Spring, MD; Vanessa A Fabrizio, Memorial Sloan Kettering Cancer Center; Vasant Chinnabhandar, University of Minnesota, Minneapolis; Yasemin A Goksenin, University of California San Francisco; Kevin J Curran, Memorial Sloan Kettering Cancer Center, New York; Crystal L Mackall, Stanford University; Theodore W Laetsch, University of Texas Southwestern Medical Center/Children’s Health, Dallas; Liora M Schultz, Stanford University
• Journal Title: BLOOD ADVANCES
• Volume: Volume 7, Number 4
• Publisher: ELSEVIER | 2023-02-23, Pages 541-548
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1182/bloodadvances.2022007246
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Hematology; CHIMERIC ANTIGEN RECEPTOR; T-CELLS

Abstract

Remarkable complete response rates have been shown with tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting CD19, in patients up to age 26 years with refractory/ relapsed B-cell acute lymphoblastic leukemia; it is US Food and Drug Administration approved for this indication. Currently, patients receive a single dose of tisagenlecleucel across a wide dose range of 0.2 to 5.0 × 106 and 0.1 to 2.5 × 108 CAR T cells per kg for patients ≤50 and >50 kg, respectively. The effect of cell dose on survival and remission is not yet well established. Our primary goal was to determine if CAR T-cell dose affects overall survival (OS), event-free survival (EFS), or relapse-free-survival (RFS) in tisagenlecleucel recipients. Retrospective data were collected from Pediatric Real World CAR Consortium member institutions and included 185 patients infused with commercial tisagenlecleucel. The median dose of viable transduced CAR T cells was 1.7 × 106 CAR T cells per kg. To assess the impact of cell dose, we divided responders into dose quartiles: 0.134 to 1.300 × 106 (n = 48 [27%]), 1.301 to 1.700 × 106 (n = 46 [26%]), 1.701 to 2.400 × 106 (n = 43 [24%]), and 2.401 to 5.100 × 106 (n = 43 [24%]). OS, EFS, and RFS were improved in patients who received higher doses of tisagenlecleucel (P = .031, .0079, and .0045, respectively). Higher doses of tisagenlecleucel were not associated with increased toxicity. Because the current tisagenlecleucel package insert dose range remains broad, this work has implications in regard to targeting higher cell doses, within the approved dose range, to optimize patients’ potential for long-standing remission.