CAR T-cell therapy promising across age groups in refractory ALL setting
medwireNews: Autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy leads to high remission rates and durable responses in children, young adults, and adults with refractory acute lymphoblastic leukemia (ALL), indicate two reports appearing in The New England Journal of Medicine.
The first study, a multicenter phase II trial, enrolled 92 patients aged 3–23 years with relapsed or refractory B-cell ALL. The CAR T-cell product tisagenlecleucel (CTL019) was successfully generated and administered to 75 participants who were followed up for a minimum of 3.0 months and a median of 13.1 months.
Shannon Maude, from the Children’s Hospital of Philadelphia in Pennsylvania, USA, and co-researchers report that the overall remission rate was 81%, with 60% of participants achieving complete remission and 21% achieving complete remission with incomplete hematologic recovery. The median duration of response was unreached.
At the 6-month mark, 73% of patients were event-free and 90% were alive, while the corresponding rates at 12 months after infusion were 50% and 76%.
The study authors note that these efficacy results “compare favorably with the rates achieved with [US] Food and Drug Administration–approved agents for relapsed B-cell ALL,” but they come with a “substantial” risk for adverse events.
Specifically, grade 3 or 4 effects related to tisagenlecleucel occurred in 73% of participants, primarily within 8 weeks of infusion, becoming less frequent by 1 year.
The cytokine release syndrome was reported in 77% of patients, nearly half of whom required admittance to the intensive care unit. A variety of measures were used to manage the syndrome in these patients, including high-dose vasopressors in 25%, tocilizumab in 37%, and oxygen supplementation in 44%.
Forty percent of participants experienced a neurologic event within 8 weeks of infusion, with grade 3 events occurring in 13%, but no incidence of grade 4 events or cerebral edema.
The second study reported on the long-term follow-up of 53 adults (23–74 years) with relapsed or refractory B-cell ALL who received an infusion of autologous 19-28z CAR T cells at a US center.
The median follow-up for the phase I trial was 29 months, during which 83% of participants had a complete remission, while the median event-free survival (EFS) and overall survival (OS) times were 6.1 and 12.9 months, respectively.
The toxicity profile of the CAR T-cell therapy was similar to that in the pediatric and young adult study, with the cytokine release syndrome occurring in 85% of study participants (grade ≥3 in 26%) and neurotoxicity seen in 44% (grade ≥3 in 42%). One patient died as a result of severe cytokine release syndrome, but no patient experienced a grade 5 neurologic event or cerebral edema.
Lead author Michel Sadelain (Memorial Sloan Kettering Cancer Center, New York, USA) and co-workers suggest that pretreatment disease could be a “useful predictor of remission duration and survival.”
Specifically, patients with a low disease burden (<5% bone marrow blasts) had significantly longer EFS and OS than those with a high disease burden (≥5% bone marrow blasts or extramedullary disease), at 10.6 versus 5.3 months and 20.1 versus 12.4 months, respectively.
Patients with a low disease burden were also significantly less likely to experience severe cytokine release syndrome and neurotoxic effects.
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