Jae Park, MD

WASHINGTON, DC—Results of a retrospective study suggest pretreatment disease burden impacts the outcome of chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).

Patients who had minimal residual disease (MRD) prior to treatment had superior event-free and overall survival compared to patients who had morphologic disease before treatment.

Patients with MRD were also less likely to experience cytokine release syndrome (CRS) and neurologic toxicity.

Jae Park, MD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York, New York, presented these results at the AACR Annual Meeting 2017 (abstract CT078).

This study was funded by Juno Therapeutics, the National Cancer Institute, the Terry Fox Foundation, and MSKCC Experimental Therapeutics Center.

“[W]e and other groups have developed and tested CD19-specific [19-28z] CAR T-cell therapy and have reported encouraging results, with high initial complete response rates in patients with B-ALL,” Dr Park said.

“However, relapses are common, even after achieving seemingly deep remission, and severe toxicities have been observed in some patients.”

To gain more insight into these results, Dr Park and his colleagues retrospectively analyzed data from a prospective clinical trial that tested 19-28z CAR T-cell therapy in patients with B-ALL.

All 51 adults in this trial had relapsed after or were refractory to 1 or more conventional multiagent chemotherapy regimens.

The researchers measured disease burden prior to CAR T-cell infusion in all patients and divided them into 2 cohorts:

20 patients who had MRD—less than 5% blasts in the bone marrow

31 patients who had morphologic disease—5% or more blasts in the bone marrow.

Response and survival

The complete response rate was 95% in the MRD cohort and 77% in the morphologic disease cohort, a difference that was not statistically significant.

At a median follow-up of 18 months, the median event-free survival and overall survival had not been reached for patients in the MRD cohort (because most were still alive and disease-free).

However, for patients in the morphologic disease cohort, the median event-free survival was 6.3 months (P=0.0005), and the median overall survival was 17 months (P=0.0189).

Role of transplant

The researchers found that long-term survival did not improve for patients who proceeded to hematopoietic stem cell transplant (HSCT), regardless of their disease burden at baseline.

“While more patients and longer follow-up will be needed to adequately address the significance of HSCT, the result of this analysis raises a question as to whether 19-28z CAR therapy can be considered as a definitive, curative therapy rather than a bridge to stem cell transplant, at least in a subset of patients,” Dr Park noted.

“Our data suggest that incorporation of 19-28z CAR T cells at the time of MRD following first-line chemotherapy will maximize the durability of CAR T-cell-mediated remissions and survival and can potentially spare these high-risk patients from HSCT, rather than waiting until they relapse morphologically and then trying CAR T-cell therapy when it is less likely to achieve a durable long-term outcome.”

Adverse events and limitations

Patients from the MRD cohort fared better than the morphologic disease cohort in terms of CRS and neurologic toxicity.

Forty-two percent of patients in the morphologic disease cohort developed CRS, compared to 5% of patients in the MRD cohort (P=0.0326).

Neurologic toxicity occurred in 58% of patients in the morphologic disease cohort and 15% of those in the MRD cohort (P=0.0001).

Dr Park noted that a limitation of this study is its retrospective nature, and the findings will need to be validated prospectively.

Furthermore, the analysis on the impact of allogeneic HSCT was limited by a relatively small sample size in each cohort.

Disease burden impacts outcome of CAR T-cell therapy in B-ALL