Analysis Informs Need for New Staging, Therapeutic Evaluations for EMD in B-ALL Prior to CAR T-Cell Therapy

New findings with extramedullary disease (EMD) involvement in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) may demonstrate the need for new staging and therapeutic evaluations with the administration of chimeric antigen receptor (CAR) T-cell therapy.

Clinicians from Seattle Children’s, Children’s Hospital of Philadelphia, National Cancer Institute, and other institutions characterized responses in patients with central nervous system (CNS) and non-CNS EMDin B-ALLto improve clinical care and response to relapse after CAR T-cell therapy.

Their findings were presented by Susan Rheingold, MD, medical Director, Oncology Outpatient Clinic and Attending Physician, Cancer Center, Children's Hospital of Philadelphia, at the 2024 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in San Antonio, Texas, February 21-24, 2024.

“Barrow marrow responses to CD19-targeted CAR T-cells are well established and really have revolutionized outcomes in B-ALL, unfortunately, the data on extramedullary for CNS and non CNS response to CAR-T is lacking, therefore sites of non CNS EMD are not routinely assessed during pre-CAR T evaluations and are only identified symptomatically or incidentally,” Rheingold said during her presentation.

Rheingold and colleagues analyzed data from 290 patients, 225 (77.6%) with no EMD or CNS involvement and 25 (22.4%) with EMD or CNS involvement. Of the latter group, 35 (53.8%) had CNS involvement, 25 (38.4%) had non-CNS EMD, and 5 (7.7%) had CNS involvement and EMD.Looking broadly, there were statistically significant reductions in 2-year overall survival (OS) and event-free survival (EFS) between patients with any CNS or EMD involvement compared to those without (OS: 63.5% vs 71.8%; P = .056; EFS: 34.1% vs 54.3%; P = .0015).¹

“BM disease burden is an important prognostic factor. Combined BM disease and CNS or non-CNS EMD represent a group with poor long-term outcomes after CAR-T,” Rheingold said.

Patients with high bone marrow (BM) burden experienced the worst outcomes in the analysis, with a 33.3% 2-year OS and 14.3% EFS in patients with high BM burden with CNS disease and a 50.0% 2-year OS and 21.4% EFS in patients with high BM burden and non-CNS EMD. Comparatively, patients with low BM burden with CNS disease had a 100% 2-year OS (P = .0028) and 57.7% EFS (P = .0006) and patients with low BM burden with non-CNS EMD had a 100% 2-year OS (P = .046) and 58.4% EFS (P = .017). Rheingold and colleagues did not find significant differences between outcomes with patients with low BM burden CNS disease or EMD with/without minimal residual disease (MRD) negativity.¹

“Sites and presentations of non-CNS EMD in patients with B-ALL are diverse and oncologist and transplanters must be aware of this to promptly investigate unusual sites of relapse. CNS and non-CNS EMD can be effectively treated with CART, but EFS is decreased when compared to BM-only relapses,” Rheingold concluded. “Consideration should be made to minimize BM disease as much as possible in patients with concomitant CNS and non-CNS EMD disease. Lastly, although probably not financially feasible, considerations should be made to look for EMD prior to infusion given its potential impact on prognosis.

Click here to view more coverage of the 2024 Tandem meeting.

REFERENCE

1. Rankin AW, Myers RM, Lamble A, et al. Characterization of Extramedullary Disease (EMD) Response to CD19 Targeted Chimeric Antigen Receptor T-Cells (CART) in Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (B-ALL): A Multi-Site, Retrospective Cohort Review. Presented at: Presented at: 2024 Tandem Meetings, February 21-24, San Antonio, Texas. Abstract #104.