Sarkisian, Angela

Shah, Nirali N.

Silbert, Sara K.

Steinberg, Seth M.

Yates, Bonnie

English

George Washington University: Health Sciences Research Commons (HSRC)

Evaluating the Prognostic Utility of the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) in Children and Young Adults with Relapsed Refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL) Prior to CAR T-Cell TherapyAngela Sarkisian, MSc1,2, Seth M. Steinberg, PhD3, Bonnie Yates, MSN, CNP1, Nirali N. Shah, MD, MHSc1 and Sara K. Silbert, MD1, 1Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD, 2George Washington University School of Medicine and Health Sciences, Washington, DC, 3Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MDIntroductionAimsMethodsResultsConclusionsFuture StepsReferencesAcknowledgmentsContact InformationSorror ML. How I assess comorbidities before hematopoietic cell transplantation. Blood. 2013 Apr 11;121(15):2854-63. doi: 10.1182/blood-2012-09-455063. Epub 2013 Jan 25. PMID: 23355537Smith AR, Majhail NS, MacMillan ML, DeFor TE, Jodele S, Lehmann LE, Krance R, Davies SM. Hematopoietic cell transplantation comorbidity index predicts transplantation outcomes in pediatric patients. Blood. 2011 Mar 3;117(9):2728-34. doi: 10.1182/blood-2010-08-303263. Epub 2011 Jan 12. PMID: 21228326Table 1: HCT-CI in Relation to OutcomesAll Patients (n=119)HCT-CI 0 (n=20) HCT-CI 1-2 (n=40) HCT-CI 3+ (n=59) PAny CRSYes 96 15 31 500.28No 23 5 9 9CRS by Max Grade0 23 5 9 90.371 45 8 13 242 30 5 10 153 17 2 6 94 4 0 2 2Complete ResponseYes 82 16 27 390.29No 36 4 12 20Median OS 14.6 mos (9.9-38.7)18.8 mos (7.3-27.4)12.2 mos (7.9-14.9)0.392yr CIR49.3% (95% CI: 19.9-73.4%)64.6%(95% CI: 41.9-80.3%)61.6%(95% CI 42.2-76.2%) 0.36Thank you to the NCI-CCR, POB, and Nirali Shah’s team in the Hematologic Malignancies Section for their support of this project. A special thank you to our patients, families, and referring teams!Questions/Comments can be directed to:Sara Silbert, MDsara.silbert@nih.gov• CAR T-Cells have demonstrated remarkable efficacy at inducing remission in children and young adults with B-cell malignancies• While remission rates are high, most experience CRS and >50% will ultimately relapse• Tools to prognosticate individual risks of post-CAR T-cell morbidity and mortality are limited• In the allogeneic hematopoietic stem cell transplant setting, the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) has been validated in adult and pediatric patients to predict both overall and event free survival• The utility of the HCT-CI in predicting post CAR T-cell outcomes remains unknown1. To calculate at HCT-CI score for a cohort of children and young adult patients receiving CAR T-Cell Therapy2. To determine if the HCT-CI is able to predict post-CAR outcomes including:• CRS• CRS Maximum Grade• Complete Response• Median Overall Survival• 2-year Cumulative Incidence of Relapse• HCT-CI score was retrospectively calculated for 119 children and young adults with r/r B-ALL• All patients were treated on 1 of 3 Phase I CAR trials at the National Cancer Institute (NCT01593696,NCT02315612, NCT0344839) through 12/31/2020 (Table 1)• Scores were calculated using data collected prior to initiation of lymphodepleting chemotherapy• Scores were analyzed with respect to outcome measures including cytokine release syndrome (CRS), complete response (CR), median overall survival (OS) and cumulative incidence of relapse (CIR)• Of 119 patients, median age was 15.4 (range 4.4-30.7) and median number of prior cycles of therapy (excluding HCT) was 5 (range 1-14).• Median HCT-CI was 2 (range 0-7); 49.6% of patients had a score > 3• Each patient had a median of 1 comorbidity (range 1-3)• Hepatic and pulmonary systems were the predominant contributors to HCT-CI scores (Figure 1)• There was no association between HCT-CI and CRS incidence, CRS maximum grade, CR, median OS (Figure 2), nor 2-year CIR (Figure 3)• The HCT-CI lacks prognostic utility in predicting post CAR T-Cell outcomes in children and young adults with r/r B-ALL• A different set of comorbidities, alongside known determinants of response and toxicities (ie. disease burden) may be important in predicting outcomes• Generation and validation of a CAR-CI that uses a combination of CAR specific comorbidities with biomarker and disease-based risk factors to predict post-CAR morbidity and mortality Figure 2: Overall Survival by HCT-CI Figure 3: Cumulative Incidence of Relapse by HCT-CIFigure 1: System Contribution to HCT-CI Score

Evaluating the Prognostic Utility of the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) in Children and Young Adults with Relapsed Refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL) Prior to CAR T-Cell Therapy

https://hsrc.himmelfarb.gwu.edu/cgi/viewcontent.cgi?article=1255&context=gw_research_showcase

Evaluating the Prognostic Utility of the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) in Children and Young Adults with Relapsed Refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL) Prior to CAR T-Cell Therapy

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