Patients with high bone marrow burden and CNS/non-CNS EMD were found to experience the worst OS and EFS outcomes.
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.
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Bendamustine Is an Effective Alternative to Fludarabine-Based Lymphodepletion in LBCL
December 7th 2024In the wake of fludarabine shortages, lemphodepletion with bendamustine was found to be an effective alternative compared for patients with large B-cell lymphoma being treated with a CD19-directed CAR T-cell therapy.