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TOPLINE: 

CD19 chimeric antigen receptor (CAR) T-cell therapy achieved high response rates in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and extramedullary disease or central nervous system (CNS) involvement, according to a retrospective review. More than 80% of patients achieved clearance of their extramedullary or CNS disease; however, patients with concurrent high bone marrow disease burden experienced significantly worse survival than those with low bone marrow burden.

METHODOLOGY:

• CD19 CAR T-cell therapy is the standard of care for patients with marrow relapsed/refractory B-ALL, but data on their effectiveness in patients with CNS involvement or extramedullary leukemia outside the CNS are limited.
• Researchers conducted a retrospective, multicenter review of 308 children and young adults (≤ 25 years at diagnosis) who received CD19 CAR T-cell therapy for relapsed/refractory B-ALL across four large pediatric CAR T-cell programs in the US between January 2012 and December 2022.
• Patients were stratified into three cohorts based on disease location at infusion: those with active extramedullary disease with or without bone marrow disease (n = 21), those with active CNS2/3 disease with or without bone marrow disease (n = 36), and those with isolated bone marrow disease without active extramedullary or CNS disease (n = 251). Bone marrow disease burden was classified as high (≥ 5% blasts) or low (< 5% blasts) at the most recent evaluation prior to CD19 CAR T-cell infusion; CNS involvement was defined as CNS2 or CNS3 disease, and extramedullary disease was defined as focal disease outside the bone marrow or CNS.
• The study outcomes included overall survival and event-free survival at 24 months. Response was assessed at 21-28 days post-infusion, with bone marrow complete response defined as < 5% blasts and measurable residual disease negativity defined as blasts constituting < 0.01% of bone marrow mononuclear cells and/or total white blood cells.

TAKEAWAY:

• Overall and event-free survival differed across cohorts. The 24-month overall survival rates were 71.5% in the isolated bone marrow cohort, 66.7% in the extramedullary disease cohort, and 57.0% in the CNS cohort (P = .032), with corresponding event-free survival rates of 51.8%, 45.8%, and 35.2%, respectively (P = .035).
• Among 208 evaluable patients with marrow disease at infusion, measurable residual disease -negative rates were 75% in the extramedullary disease cohort, 84% in the CNS cohort, and 93.4% in the isolated bone marrow cohort (P = .019). For patients with > 5% blasts, rates were 66.7%, 75.0%, and 90.7%, respectively (P = .012). Among evaluable patients, 82.4% with extramedullary disease achieved complete response and 87.5% with CNS involvement achieved remission.
• The poorest outcomes were seen among patients with concurrent extramedullary or CNS disease and high bone marrow disease burden. Compared with low marrow burden, high bone marrow disease burden with concurrent extramedullary disease was associated with significantly worse 24-month overall survival (41.7% vs 100%; P = .005) and event-free survival (8.3% vs 100%; P < .001). Similarly, high vs low bone marrow disease burden with concurrent CNS disease was associated with worse 24-month overall survival (33.3% vs 92.3%; hazard ratio [HR] for death, 6.55) and event-free survival (14.3% vs 63.6%; HR for an event, 5.34).
• Any-grade cytokine release syndrome occurred in 90.5% of the extramedullary disease cohort, 80.5% of the CNS cohort, and 80.0% of the isolated bone marrow cohort (P = .900); grade ≥ 3 cytokine release syndrome affected 19.1%, 22.2%, and 15.1%, respectively. Any-grade neurotoxicity was reported in 33.3%, 52.8%, and 41.0% of the three cohorts, respectively.

IN PRACTICE:

While “CD19 CAR may be an effective option for certain patients,” those with active extramedullary disease or CNS disease and high bone marrow disease burden “seem to have inferior outcomes,” the authors explained.

“These results highlight the need for prospective studies that investigate the utility of screening for [extramedullary disease] in certain high-risk patients, the impact of bridging therapies on the outcomes of those with extramedullary involvement, and the mechanistic underpinnings of CD19 CAR efficacy in extramedullary B-ALL.”

SOURCE:

The study, led by Alexander W. Rankin, Division of Hematology, Oncology & Blood and Marrow Transplant, Nationwide Children’s Hospital in Columbus, Ohio, was published online in Blood Advances.

LIMITATIONS:

The study was retrospective and, therefore, subject to missing data and unmeasured confounding. Extramedullary disease and CNS cohorts were small, which limited subgroup analysis.Screening for non-CNS extramedullary disease was not uniform across centers so occult extramedullary disease may have been missed and some patients in the isolated bone marrow cohort may have been misclassified.

DISCLOSURES:

This work was supported, in part, by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, and the National Institutes of Health Clinical Center. Some authors reported receiving research support or having consulting relationships and other ties with various sources, including Vertex, Novartis, Servier, Cellectis, Allogene, Adaptive Biotechnologies, Beam Therapeutics, Cabaletta Bio, Estrella Immunopharma, and others. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.