Survival after first relapse of pediatric B-ALL differs by insurance type: A real-world analysis from the recall-1 study
Abstract
Abstract BACKGROUND Children exposed to poverty during frontline therapy for B-lymphoblastic leukemia (B-ALL) experience inferior overall survival (OS), higher relapse rates, and earlier relapse than their peers. Real-world data describing treatment patterns and survival after relapse of B-ALL are lacking and, as a result, the impact of poverty following relapse remains poorly understood. This study evaluated the association of poverty exposure, proxied by insurance status, with post-relapse survival and explored potential explanatory mechanisms, including disease biology and therapy utilization. METHODS Data from Retrospective Study of Contemporary Approaches to First Relapse in B-ALL (ReCALL-1), a multicenter retrospective cohort study of patients < 30 years old with first relapse of B-ALL from 2018-2022, were used. The primary exposure was poverty, proxied by insurance status at relapse, categorized as any private insurance (poverty unexposed), public-only insurance (poverty exposed), no insurance, or unknown; the latter two were not included in comparative analyses due to low numbers. The primary outcome was OS. Secondary outcomes included measurable residual disease (MRD)-negative second complete remission (CR2), relapse after CR2, non-relapse mortality (NRM), with relapse treated as a competing risk, and receipt of cellular and immunotherapies. RESULTS Among 462 patients from 31 U.S. institutions, 41% had private insurance, 47% public-only insurance, 2% no insurance, and 10% unknown. Compared to privately insured patients, those with public insurance were more likely to be Hispanic (56% vs 19%, p<0.001) and have non-English preferred language (30% vs 6%, p<0.001). Non-Hispanic Black patients comprised 9% of those with public insurance and 5% of those with private insurance. Disease characteristics that differed by insurance status at relapse included: Ph-like cytogenetics, more common in publicly insured (23% vs 11%, p=0.002), and infant ALL, more common in privately insured patients (10% vs 5%, p=0.06). Publicly insured patients were more likely to have experienced major organ toxicity during frontline therapy (32% vs 18%, p=0.002) and very early relapse (<18m from diagnosis: 43% vs 32%, p=0.07). Other demographic and disease characteristics, including relapse site and cytomolecular features, were similar by insurance status. With a median follow-up of 51 months from relapse, 4-year OS differed by insurance (log-rank p=0.02): 72% for private vs 56% for public insurance. After adjusting for race/ethnicity and language, public insurance increased the hazard of death by 65% (aHR 1.65 95% CI 1.13-2.42, p=0.004). The association remained, but was attenuated, when unbalanced disease characteristics (time to relapse, infant ALL, Ph-like cytogenetics, prior organ dysfunction) were included (aHR 1.47, 95% CI 1.00-2.16, p=0.05). Rates of MRD-negative CR2 were similar (85% public vs 87% private). However, point estimates suggested publicly insured patients had more relapse after CR2 (44% vs 37%, p=0.42) and higher 4-year NRM (16% vs 10%, Gray's test p=0.12), though neither were significant. Treatment choices for first relapse did not differ by insurance status. Utilization of intensive reinduction (91% vs 95% for public vs private, p=0.18) and clinical trial enrollment (22% for both) were similar. Receipt of cellular therapies did not significantly differ by public vs private insurance: Chimeric Antigen Receptor-T cells (CAR-T: 38% vs 34%, p=0.41), hematopoietic cell transplant (HCT: 42% vs 47%, p=0.32). Use of blinatumomab trended higher in those with private insurance (36% vs 45%, p=0.07), and inotuzumab was similar (11% for both, p=0.87). Median time from relapse to CAR-T or HCT was comparable (to CAR-T 102 vs 100 days, to HCT 117 vs 114 days). CONCLUSION This is the first study to demonstrate differential survival by insurance type, a proxy for poverty exposure, after first relapse of B-ALL. In this large multicenter, real-world cohort, patients with public insurance had worse OS after relapse than those with private insurance. The survival disparity existed independent of other SDOH factors. Adjustment for known high-risk disease features only partially accounted for the observed differences in OS. In contrast, rates of MRD-negative CR2 and receipt of CAR-T and HCT were comparable across insurance types. These findings highlight the urgent need to identify effective interventions that will ensure equitable outcomes after relapse.
Article Details
Authors (60)
Katherine Lind
17Children's Hospital of Colorado, Center for Cancer and Blood Disorders, Department of Pediatrics, Aurora, United States
Abigale Berry
1Children's Hospital of Philadelphia, Division of Oncology, Philadelphia, United States
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
Jeremy Rubinstein
33Cincinnati Children's Hospital Medical Center, Division of Oncology, Cincinnati, United States
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
Anurekha Hall
12Seattle Children's Hospital, Seattle, WA, Division of Oncology, Seattle, United States
Deepa Bhojwani
Troy Quigg
2Section of Pediatric Bone Marrow Transplantation and Cellular Therapy, Helen DeVos Children's Hospital, Grand Rapids, United States
Shannon Maude
1Children's Hospital of Philadelphia, Division of Oncology, Philadelphia, United States
Nirali Shah
32National Cancer Institute, Pediatric Oncology Branch, Bethesda, United States
Maria Ortega
19Nemours Children's Health, Lisa Dean Moseley Foundation for Cancer and Blood Disorders, Wilmington, United States
Abdulla Al-Mulla
7Children's Hospital of Richmond at VCU, Division of Oncology, Richmond, United States
Ibrahim Ahmed
Jill Beck
9University of Nebraska Medical Center, Division of Pediatric Hematology/Oncology, Omaha, United States
Deepika Bhatla
10Cardinal Glennon Children's Hospital, Division of Oncology, Saint Louis, United States
Eliza Briscoe
11University of Utah/Primary Children's Hospital, Department of Pediatrics, Salt Lake City, United States
Roland Chu
13Children's Hospital of Michigan, Division of Pediatric Hematology/Oncology, Detroit, United States
Laurie Davis
14Baylor College of Medicine, Division of Blood and Marrow Transplant, San Antonio, 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
Jennifer Drinkwine
8Seattle Children's Hospital, Seattle, United States
Anna Elias
4Mayo Clinic Children's, Division of Pediatric Hematology-Oncology, Rochester, United States
Lyannette Elo
14Baylor College of Medicine, Division of Blood and Marrow Transplant, San Antonio, United States
Elizabeth Eom
15Children's Hospital Los Angeles, Division of Hematology-Oncology, Los Angeles, United States
Kelly Faulk
17Children's Hospital of Colorado, Center for Cancer and Blood Disorders, Department of Pediatrics, Aurora, United States
Erin Goode
2Peter MacCallum Cancer Centre, Department of Pathology, Melbourne, Australia
Darcy Hamill
Miza Salim Hammoud
Ashley Hinson
3Atrium Health Levine Children's Hospital, Department of Pediatric Hematology and Oncology, Charlotte, United States
Alex Hoover
Hannah Kinoshita
21Children's National Hospital, Center for Cancer and Blood Disorders, Washington, United States
Mira Kohorst
4Mayo Clinic Children's, Division of Pediatric Hematology-Oncology, Rochester, United States
Elizabeth Krieger
3Virginia Commonwealth University, Department of Pediatrics, Richmond, United States
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
Kevin McNerney
Jordan Milner
11Department of Pediatrics, Division of Hematology/Oncology, University of Florida, UF Health Shands Children's Hospital, Gainesville, 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
Lindsey Murphy
1City of Hope, Pediatrics, Duarte, United States
Megan Murphy
25Johns Hopkins Hospital, Division of Pediatric Oncology, Department of Oncology, Baltimore, United States
Hiren Patel
26Cohen Children's Medical Center, Division of Pediatric Hematology/Oncology and Cellular Therapy, New Hyde Park, United States
Thomas Pfeiffer
Alexandra Prosser-Dombrowski
6Children's Mercy Kansas City, Division of Hematology/Oncology/Bone Marrow Transplant, Kansas City, United States
Mahvish Rahim
28Children's Hospital at Montefiore, Division of Pediatric Hematology, Oncology, and Stem Cell Transplant, Bronx, United States
April Rahrig
29Riley Hospital for Children, Division of Pediatric Hematology, Oncology and Stem Cell Transplant, Indianapolis, United States
Amanda Saraf
1Riley Children's Health, Indianapolis, United States
Jamie Shoag
31Cleveland Clinic Children's, Division of Pediatric Hematology and Oncology, Cleveland, United States
Heather Symons
25Johns Hopkins Hospital, Division of Pediatric Oncology, Department of Oncology, Baltimore, United States
Nicholas Tastet
3Atrium Health Levine Children's Hospital, Department of Pediatric Hematology and Oncology, Charlotte, United States
Stephanie Thomas
20Arkansas Children's Hospital, Pediatric Oncology, Bone Marrow Transplant and Cellular Therapies, Little Rock, United States
Molly Thornock
2City of Hope, Population Sciences, Duarte, United States
Keri Toner
21Children's National Hospital, Center for Cancer and Blood Disorders, Washington, United States
Smitha Vasanna
20Arkansas Children's Hospital, Pediatric Oncology, Bone Marrow Transplant and Cellular Therapies, Little Rock, United States
Alejandra Escobar Vasco
16Medical College of Wisconsin, Division of Pediatric Hematology/Oncology/Blood and Marrow Transplant, Department of Pediatrics, Milwaukee, 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
Sara Zarnegar-Lumley
8Lurie Children's Hospital, Division of Hematology, Oncology, Neuro-Oncology, & Stem-Cell Transplant, Chicago, United States
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
Caitlin Elgarten
University of Pennsylvania, Philadelphia