Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster III
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Biological therapies, Chimeric Antigen Receptor (CAR)-T Cell Therapies, pediatric, Diseases, Therapies, Lymphoid Malignancies, Adverse Events, young adult , Study Population, Human
Objective: Establish real world disease response and toxicity outcomes experienced by overweight/obese pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) treated with chimeric antigen receptor T-cell therapy (tisagenlecleucel), compared to their healthy weight peers.
Design/Methods: Retrospective data was collected from Pediatric Real World CAR Consortium (PRWCC) institutions (n=15) on 168 pediatric/young adult patients (age 2-22), evaluable for BMI measure, who underwent infusion of commercially manufactured tisagenlecleucel for r/r B-ALL. Weight categories were established using CDC growth charts with gender/age specific BMI cutoffs (healthy 5th to 85th percentile; overweight/obese >85th percentile). Efficacy outcomes include relapse-free survival (RFS) and overall survival (OS). Toxicity endpoints include cytokine release syndrome (CRS) and neurotoxicity (ICANS). Demographic, baseline characteristics, and toxicities were summarized as median (range) for continuous variables and number and percentage for categorical variables. Comparisons between groups were done using Chi-square tests for categorical variables, or Wilcoxon test for continuous variables. The Kaplan-Meier method was used to analyze RFS and OS using the log rank test to compare weight groups. Hazard ratios with 95% confidence intervals were calculated. Univariable and multivariable analyses were performed.
Results: Of 168 patients included in the analysis, 88 were in the healthy weight category and 80 were in the overweight/obese category. There was no difference in baseline characteristics between groups (age at infusion, gender, race/ethnicity, Down syndrome, marrow morphology prior to infusion (M1 vs >M1 marrow), CNS status prior to infusion, or transplant following infusion). Overweight/obese patients had statistically significant inferior RFS at 6 months (61.9% vs 81.5%), 12 months (51.4% vs 70%), and 24 months (31.1% vs 64.7%). Relapse hazard ratio for obese/overweight patients was 2.04 (95% CI 1.2, 3.45: p = 0.006). Overall survival of overweight/obese patients was not statistically different than healthy weight patients but trended towards decreased OS in overweight/obese patients at 6 months (82.4% vs 89.6%), 12 months (70.3% vs 77.5%) and 24 months (46.4% vs 64.7%). OS hazard ratio for obese/overweight patients was 1.54 (95% CI 0.85, 2.78: p = 0.149). Additionally, overweight/obese patients showed a trend towards higher grade toxicity than healthy weight patients with CRS grade ≥ 3 seen in 22.8% vs 14.8% (p = 0.272) and ICANS grade ≥ 3 seen in 11.4% vs 3.4% (p = 0.108), respectively.
Conclusion: This retrospective, multi-institutional analysis highlights the high incidence of obesity among patients who are candidates for tisagenlecleucel. Furthermore, it shows that overweight/obese patients treated with tisagenlecleucel for r/r B-ALL have inferior outcomes (particularly RFS) and potential for increased toxicity compared to their healthy weight peers. Additional research is needed to interrogate generalizability of findings to immunotherapy recipients of all ages, across cancer subtypes, and illicit the mechanism of obesity induced immune dysfunction and related mitigating strategies.
Disclosures: Stefanski: Novartis: Other: Ad Board, Speakers Bureau. Verneris: Up-To-Date: Consultancy; Bmogen: Consultancy, Current equity holder in private company; Fate Therapeutics: Consultancy, Current equity holder in private company; Novartis: Membership on an entity's Board of Directors or advisory committees. Myers: Eliana Trial: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Qayed: Vertex: Honoraria; Novartis: Honoraria. Hermiston: Novartis: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees. Satwani: Takeda: Honoraria; Mesoblast: Honoraria. Curran: Novartis: Consultancy, Research Funding. Mackall: Immatics: Consultancy; Medimmune Tech: Consultancy; Nektar: Consultancy; Syncopation: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months; Link: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months; Ensoma: Divested equity in a private or publicly-traded company in the past 24 months; Mammoth: Divested equity in a private or publicly-traded company in the past 24 months; BMS: Consultancy; Apricity: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months; GSK: Consultancy; Lyell Pharmaceuticals: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months. Laetsch: Novartis: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Cellectis: Consultancy; Pfizer: Research Funding; Advanced Microbubbles: Current holder of stock options in a privately-held company; AI Therapeutics: Consultancy; Deciphera: Consultancy; GentiBio: Consultancy; Jazz Pharmaceuticals: Consultancy; Jumo Health: Consultancy; Massive Bio: Consultancy; Menarini: Consultancy; Pyramid Biosciences: Consultancy; y-mAbs Therapeutics: Consultancy. Maude: Novartis Pharmaceuticals: Consultancy, Other: study steering committee, Patents & Royalties: Patent pending and licensed to Novartis Pharmaceuticals for PCT/US2017/044425: Combination Therapies of Car and PD-1 Inhibitors , Research Funding; Wugen: Research Funding. Henry: PureTech Health: Research Funding. Schultz: Novartis: Membership on an entity's Board of Directors or advisory committees.
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