Disparate post-relapse survival outcomes by race/ethnicity for children with B-cell acute lymphoblastic leukemia: An analysis from the recall-1 study
Abstract
Abstract Introduction Pronounced disparities in pediatric B-lymphoblastic leukemia (B-ALL) outcomes by race and ethnicity persist in the contemporary era. Gaps in overall survival (OS) from initial diagnosis are wider than event-free survival, suggesting that post-relapse mechanisms may contribute. However, data on treatment and outcomes after relapse are lacking. In a large, multicenter, real-world cohort of children and young adults with high-risk 1st relapse of B-ALL, we sought to (1) define survival outcomes by race/ethnicity and (2) explore if differences in therapy utilization drive outcomes. Methods We conducted an analysis within the Retrospective Study of Contemporary Approaches to 1st Relapse in B-ALL (ReCALL-1) cohort, which includes patients <30 years who initiated 1st relapse therapy between 2018-2022. This analysis was restricted to patients treated at US centers for “high-risk” 1st relapse, defined as relapse for which hematopoietic cell transplant (HCT) is generally standard-of-care: Early relapse (medullary <36m; isolated extramedullary <18m), late relapse with persistent end of reinduction disease, Ph+ B-ALL or age ≥18 years. Patients with Trisomy 21, those who received cell therapy before relapse and those who died during reinduction were excluded. The primary exposure was race/ethnicity categorized as Hispanic, non-Hispanic Black (NHB), non-Hispanic White (NHW), and other/unknown. The primary outcome was OS from relapse. Multivariable Cox regression models were constructed to include other social drivers of health (SDOH; health insurance, preferred language) and disease characteristics. Results Of 479 patients in ReCALL-1, 311 from 31 centers met inclusion for this analysis (41% Hispanic, 7% NHB, 46% NHW, 5% NH-other/unknown). With a median follow-up of 47m, OS differed by race/ethnicity (log-rank p=0.017): Hispanic, 4y OS 59%; NHB, 37%; NHW, 68%. Compared to NHW patients, NHB patients had an increased hazard of death (HR 2.3, 95% CI 1.3-4.3, p=0.006), while Hispanic patients were more similar to NHW patients (HR 1.3, 95% CI 0.9-2.0, p=0.16). Adjustment for SDOH only marginally attenuated the risk for NHB patients (aHR 2.0, 95% CI, 1.1-3.7, p=0.031) and led to equivalent outcomes for Hispanic patients (aHR 0.9, 95% CI, 0.5-1.5, p=0.66). Adjusting for disease characteristics that differed by race/ethnicity at p<0.2 (time to relapse, Ph+, Ph-like, KMT2Ar, age ≥18, or relapsed infant ALL) did not diminish the risk for NHB patients (aHR 2.0, 95% CI, 1.1-3.7, p=0.032) while outcomes remained equivalent for Hispanic patients (aHR 1.2, 95% CI, 0.8-1.8, p=0.40). Point estimates of cumulative incidence of non-relapse mortality (NRM) were highest in NHB patients (Hispanic, 4y NRM 13%, NHB 22%, NHW 11%), but this trend was not statistically significant (Gray’s p=0.52). Only 17% of patients initiated therapy for relapse on a clinical trial with no differences observed by race/ethnicity. Most patients received definitive treatment for relapse with either CAR T cell therapy (CART) or HCT: 79% overall, 74% Hispanic, 91% NHB, and 83% NHW. CART and HCT were utilized equally (39% and 40%, respectively) and the proportion that received each therapy did not vary by race/ethnicity. Time to CART/HCT, external referral for treatment, receipt of investigational v commercial CART, and use of post-CART consolidative HCT revealed no differences by race/ethnicity. Of the 66 patients (21%) who did not receive cell therapy, 26 had planned for CART or HCT, but did not receive due to disease progression or NRM (n=24; 12 Hispanic, 10 NHW), or insurance barriers (n=2, both Hispanic). After HCT, OS was worse for NHB patients (log-rank p=0.03) with 4y OS of 42% v 85% for NHW and 75% for Hispanic. Post-CART, 4y OS was 40% for NHB v 59% for NHW and 51% for Hispanic, but this difference was not statistically significant. Conclusion In a large real-world cohort of children with high-risk 1st relapse of B-ALL, we found a two-fold increased hazard of death for NHB patients compared to NHW patients, even after adjustment for other SDOH factors and high-risk disease features. In contrast to previous studies of adult patients, children appeared to have equal access to cell therapies across races/ethnicities. We found that Hispanic patients, who comprised >40% of the cohort, had similar survival to NHW children, suggesting that availability of cellular and immunotherapies may be mitigating historically observed disparities for children with relapsed B-ALL.
Article Details
Authors (61)
Abigale Berry
1Children's Hospital of Philadelphia, Division of Oncology, Philadelphia, United States
Caitlin Elgarten
University of Pennsylvania, Philadelphia
Yimei Li
Hongyan Liu
CAS Key Laboratory of Green Process and Engineering, State Key Laboratory of Multiphase Complex Systems, Beijing Key Laboratory of Ionic Liquids Clean Process, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
Katherine Lind
17Children's Hospital of Colorado, Center for Cancer and Blood Disorders, Department of Pediatrics, Aurora, United States
Daniel Zheng
Gabriella Nguyen
5University of Texas Southwestern Medical Center, Department of Pediatrics, Dallas, United States
Vanessa Fabrizio
6Division of Pediatric Hematology-Oncology-BMT, University of Colorado, Aurora, United States
Maria Ortega
19Nemours Children's Health, Lisa Dean Moseley Foundation for Cancer and Blood Disorders, Wilmington, United States
Jeremy Rubinstein
33Cincinnati Children's Hospital Medical Center, Division of Oncology, Cincinnati, United States
Troy Quigg
2Section of Pediatric Bone Marrow Transplantation and Cellular Therapy, Helen DeVos Children's Hospital, Grand Rapids, United States
Anurekha Hall
12Seattle Children's Hospital, Seattle, WA, Division of Oncology, Seattle, United States
Deepa Bhojwani
Nirali Shah
32National Cancer Institute, Pediatric Oncology Branch, Bethesda, United States
Shannon Maude
1Children's Hospital of Philadelphia, Division of Oncology, Philadelphia, United States
Sara Zarnegar-Lumley
8Lurie Children's Hospital, Division of Hematology, Oncology, Neuro-Oncology, & Stem-Cell Transplant, Chicago, United States
Allison Weisnicht
22University of Wisconsin School of Medicine and Public Health, Department of Pediatrics, Division of Hematology, Oncology, Transplant & Cell Therapy, Madison, United States
Keri Toner
21Children's National Hospital, Center for Cancer and Blood Disorders, Washington, United States
Molly Thornock
2City of Hope, Population Sciences, Duarte, United States
Stephanie Thomas
20Arkansas Children's Hospital, Pediatric Oncology, Bone Marrow Transplant and Cellular Therapies, Little Rock, United States
Nicholas Tastet
3Atrium Health Levine Children's Hospital, Department of Pediatric Hematology and Oncology, Charlotte, United States
Heather Symons
25Johns Hopkins Hospital, Division of Pediatric Oncology, Department of Oncology, Baltimore, United States
Jamie Shoag
31Cleveland Clinic Children's, Division of Pediatric Hematology and Oncology, Cleveland, United States
Amanda Saraf
1Riley Children's Health, Indianapolis, United States
April Rahrig
29Riley Hospital for Children, Division of Pediatric Hematology, Oncology and Stem Cell Transplant, Indianapolis, United States
Mahvish Rahim
28Children's Hospital at Montefiore, Division of Pediatric Hematology, Oncology, and Stem Cell Transplant, Bronx, United States
Alexandra Prosser-Dombrowski
6Children's Mercy Kansas City, Division of Hematology/Oncology/Bone Marrow Transplant, Kansas City, United States
Thomas Pfeiffer
Hiren Patel
26Cohen Children's Medical Center, Division of Pediatric Hematology/Oncology and Cellular Therapy, New Hyde Park, United States
Megan Murphy
25Johns Hopkins Hospital, Division of Pediatric Oncology, Department of Oncology, Baltimore, United States
Lindsey Murphy
1City of Hope, Pediatrics, Duarte, United States
Amy Moskop
16Medical College of Wisconsin, Division of Pediatric Hematology/Oncology/Blood and Marrow Transplant, Department of Pediatrics, Milwaukee, United States
Giselle Moore-Higgs
23University of Florida, Division of Oncology, Gainesville, United States
Jordan Milner
11Department of Pediatrics, Division of Hematology/Oncology, University of Florida, UF Health Shands Children's Hospital, Gainesville, United States
Kevin McNerney
Cathy Lee-Miller
22University of Wisconsin School of Medicine and Public Health, Department of Pediatrics, Division of Hematology, Oncology, Transplant & Cell Therapy, Madison, United States
Mira Kohorst
4Mayo Clinic Children's, Division of Pediatric Hematology-Oncology, Rochester, United States
Hannah Kinoshita
21Children's National Hospital, Center for Cancer and Blood Disorders, Washington, United States
Elizabeth Krieger
3Virginia Commonwealth University, Department of Pediatrics, Richmond, United States
Smitha Vasanna
20Arkansas Children's Hospital, Pediatric Oncology, Bone Marrow Transplant and Cellular Therapies, Little Rock, United States
Alex Hoover
Ashley Hinson
3Atrium Health Levine Children's Hospital, Department of Pediatric Hematology and Oncology, Charlotte, United States
Miza Salim Hammoud
Darcy Hamill
Erin Goode
2Peter MacCallum Cancer Centre, Department of Pathology, Melbourne, Australia
Kelly Faulk
17Children's Hospital of Colorado, Center for Cancer and Blood Disorders, Department of Pediatrics, Aurora, United States
Alejandra Escobar Vasco
16Medical College of Wisconsin, Division of Pediatric Hematology/Oncology/Blood and Marrow Transplant, Department of Pediatrics, Milwaukee, United States
Lyannette Elo
14Baylor College of Medicine, Division of Blood and Marrow Transplant, San Antonio, United States
Anna Elias
4Mayo Clinic Children's, Division of Pediatric Hematology-Oncology, Rochester, United States
Elizabeth Eom
15Children's Hospital Los Angeles, Division of Hematology-Oncology, Los Angeles, United States
Jennifer Drinkwine
8Seattle Children's Hospital, Seattle, United States
J. Gregory Dolan
22Division of Hematology and Oncology, Intermountain Primary Children's Hospital, Huntsman Cancer Institute, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, United States
Laurie Davis
14Baylor College of Medicine, Division of Blood and Marrow Transplant, San Antonio, United States
Roland Chu
13Children's Hospital of Michigan, Division of Pediatric Hematology/Oncology, Detroit, United States
Eliza Briscoe
11University of Utah/Primary Children's Hospital, Department of Pediatrics, Salt Lake City, United States
Deepika Bhatla
10Cardinal Glennon Children's Hospital, Division of Oncology, Saint Louis, United States
Jill Beck
9University of Nebraska Medical Center, Division of Pediatric Hematology/Oncology, Omaha, United States
Abdulla Al-Mulla
7Children's Hospital of Richmond at VCU, Division of Oncology, Richmond, United States
Ibrahim Ahmed
Lena Winestone
41University of California San Francisco Benioff Children's Hospitals, San Francisco, United States
Regina Myers
1Children's Hospital of Philadelphia, Division of Oncology, Philadelphia, United States