Targeted immunotherapy with CAR-modified T cells has produced prolonged complete responses (CRs) in children and adults with relapsed and refractory ALL. Here, researchers report outcomes after longer follow-up of 59 children and young adults with relapsed/refractory ALL enrolled in a phase 1/2a trial of CD19-specific CAR-modified T cells (CTL019). After 1 month, 93% of 59 patients are in CR with 52 of them showing minimal residual disease <0.01% by flow cytometry. Durable remissions are observed without subsequent stem-cell transplant. Severe cytokine release syndrome (CRS) occurred in 27%. CRS is associated with high disease burden and is reversed with tocilizumab, an anti–IL-6R agent.
To better understand the association between pretreatment disease burden and outcomes (tolerability, long-term efficacy) of 19-28z CAR T cells (JCAR015), a focused analysis of results from a phase 1 clinical trial of 19-28z CAR T cells in adults with relapsed and refractory B-cell ALL was performed. Patients were divided into 2 cohorts based on the blast percentage in bone marrow: minimal disease (<5%) versus morphologic disease (≥5%). This assessment confirms antitumor efficacy of JCAR015 regardless of pretreatment disease burden. Patients with <5% blasts experienced relatively less toxicity and enhanced long-term survival.
Early response to induction chemotherapy is a significant prognostic factor in the outcome of children with ALL. This study evaluates the ability of the Adaptive Biotechnologies assay of IgH and TCRG to quantify residual disease at the end of induction therapy and offer prognostic value regarding event-free survival. Researchers conclude that this high throughput sequencing assay is more sensitive than multiparametric flow cytometry in accurately predicting outcomes in children with ALL.
