Low Disease Burden Improved Durability of CAR T-Cell Therapy in B-ALL

Although most adults with relapsed B-cell acute lymphoblastic leukemia (B-ALL) experienced complete remission after treatment with 19-28z chimeric antigen receptor (CAR) T cells, those patients with a low pretreatment disease burden experienced a more durable remission, according to results (abstract CT078) presented at the American Association for Cancer Research (AACR) Annual Meeting 2017, held April 1–5 in Washington, DC.

“Our data suggest that incorporation of 19-28z CAR T cells at the time of minimal residual disease [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 hematopoietic stem cell transplant [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,” said Jae Park, MD, assistant attending physician at Memorial Sloan Kettering Cancer Center, in a press release.

According to Park, survival among adults with relapsed or refractory ALL is extremely poor. In order to develop more effective therapies for these patients, Park and others have developed and tested CD19-specific CAR T-cell therapy. This treatment has demonstrated high initial responses in patients with relapsed B-ALL; however, more data were needed to define clinical characteristics of patients who experience greater durability of response.

In this study, 51 patients received 19-28z CAR T cells. The researchers assessed disease burden by bone marrow biopsy immediately prior to T-cell infusion. Patients were grouped into two cohorts: MRD with less than 5% blasts in bone marrow; and morphologic disease (5% or greater blasts).

The two groups had similar rates of complete remission: 95% for the MRD cohort and 77% for the morphologic cohort.

However, when the researchers analyzed survival by cohort, they found that patients with MRD had significantly improved survival outcomes. The median event-free survival for MRD-negative patients with complete remission was not yet reached compared with 6.3 months for the morphologic group (P = .0005). Similarly, the median overall survival was not yet reached for the MRD group compared with 17 months for the morphologic group (P = .0189).

Subsequent transplant was found to have no effect on survival regardless of the patient cohort.

“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,” Park said.

Patients from the MRD cohort fared well in terms of side effects as well, compared with those in the morphologic disease cohort. Two of the major side effects associated with CAR T cells, cytokine release syndrome and neurotoxicity, occurred in 42% and 58% of the patients, respectively, in the morphologic disease cohort, compared with 5% and 15%, respectively, in those from the MRD cohort.