Tisagenlecleucel outcomes in relapsed/refractory extramedullary ALL: a Pediatric Real World CAR Consortium Report

Abstract

Chimeric antigen receptor (CAR) T-cells have transformed the therapeutic options for relapsed/refractory (R/R) B-cell ALL. Data for CAR therapy in extramedullary (EM) involvement is limited. Retrospective data was abstracted from the Pediatric Real World CAR Consortium (PRWCC) of 184 infused patients from 15 US institutions. Response (CR) rate, overall survival (OS), relapse-free survival (RFS), and duration of B-cell aplasia (BCA) in patients referred for tisagenlecleucel with EM disease (both CNS3 and non-CNS EM) were compared to bone marrow (BM) only. Patients with CNS disease were further stratified for comparison. Outcomes are reported on 55 patients with EM disease prior to CAR (n=40 CNS3; n=15 non-CNS EM). The median age at infusion in CNS cohort was 10 years (range <1-25) and the non-CNS EM cohort was 13 years (2-26). In patients with CNS disease, 88% (35/40) achieved a CR, versus only 66% (10/15) with non-CNS EM disease. Patients with CNS disease (both with and without marrow involvement) had comparable 24-month OS outcomes to non-CNS EM or BM only (p=0.41). There was no difference in 12-month RFS between CNS, non-CNS EM, or BM only patients (p=0.92). No increased toxicity was seen with CNS or non-CNS EM disease (p=0.3). Active CNS disease at time of infusion did not impact outcomes. Isolated (iCNS) disease trended towards improved OS when compared to combined CNS and BM (p=0.12). R/R EM disease can be effectively treated with tisagenlecleucel with toxicity, relapse rates and survival rates comparable to patients with BM only. Outcomes for iCNS relapse are encouraging.

Outcomes After Nonresponse and Relapse Post-Tisagenlecleucel in Children, Adolescents, and Young Adults With B-Cell Acute Lymphoblastic Leukemia

“…14 The PRWCC previously published outcomes using tisagenlecleucel for the treatment of EM disease and described that the presence of baseline EM disease versus BM-only disease was not a risk factor for nonresponse or relapse. 16 Here, we identify that the number of preinfusion lines of therapy is associated with increased likelihood of relapse, possibly explained by more recalcitrant tumor biology, and compromised T-cell fitness or cumulative toxicity. Clinical studies evaluating CD19-CAR in the upfront MRD+ refractory setting are ongoing (ClinicalTrials.gov identifier: NCT03876769).…”

CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany

“…This study demonstrated that CNS involvement was also not associated with impaired survival. 21 Most recently, several studies have addressed the question of the optimal bridging to CAR-T cell therapy. 22,23 The question of whether previous CD19-directed immunotherapy with blinatumomab might contribute to treatment failure has gained particular importance.…”

Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas

“…Grade ≥ 3 neutropenia is observed in <40% of patients and the cumulative incidence of neutrophil recovery at 28 days was 75%. HGG was pronounced in roughly half of the cohorts, while irAEs, pre-therapy lymphopenia, and duration of low IgG were significantly associated with infection density [ 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 ]. According to the FDA Adverse Event Reporting System for tisagenlecleucel in the post-marketing period for the pediatric population, infection was the second most frequent cause of death (11.3%) after disease progression [ 172 ].…”