Blood collection

Credit: Charles Haymond

SAN FRANCISCO—JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, can produce durable responses in patients with B-cell acute lymphoblastic leukemia (ALL) who do not undergo subsequent hematopoietic stem cell transplant (HSCT), new research suggests.

JCAR015 consists of autologous T cells genetically modified to express 19-28z chimeric antigen receptor (19-28z CAR) targeting CD19.

Jae H. Park, MD, of Memorial Sloan Kettering Cancer Center in New York, presented data on JCAR015 at the 2014 ASH Annual Meeting (abstract 382).* The study is sponsored by Memorial Sloan Kettering, but funding has also been provided by Juno Therapeutics, the company developing JCAR015.

JCAR015 was tested at a dose of 1 - 3 x 10⁶ CAR cells/kg in 33 adults with relapsed/refractory B-cell ALL. Twenty-eight patients were evaluable for toxicity, 27 for response, and 5 patients were too early in their treatment to evaluate at the time of data cutoff.

Twenty-one patients were male, and the median age was 55 (range, 23 to 74).

Thirteen patients (46%) had minimal disease (<5% blasts) immediately prior to T-cell infusion, and 15 patients (54%) had morphologic disease of 5% to 100% blasts (median 63%).

Eighteen patients (64%) had received 2 prior lines of therapy, and 5 (18%) each had 3 or more prior lines.

Eight patients (29%) underwent prior allogeneic HSCT, 9 patients (32%) were Philadelphia chromosome positive (Ph+), and 3 (11%) had the T315I mutation.

The overall complete response (CR) rate was 89%, and the minimal residual disease-negative CR rate was 88%. The median time to CR was 22.5 days (range, 9 to 33).

The investigators performed a subgroup analysis and found that 100% of the 13 patients with minimal disease before therapy achieved a CR, compared to 79% of patients with morphologic disease.

Eighty-six percent (6/7) of patients who had a prior HSCT and 90% (18/20) without a prior HSCT achieved a CR. Eighty-nine percent (8/9) of Ph+ patients achieved a CR, and 89% (16/18) of Philadelphia-negative patients (89%) achieved a CR.

At a median follow-up of 6 months (range, 1 to 38 months), 12 patients remained disease-free, including 7 patients who had more than a year of follow-up. Seven patients are disease-free without a subsequent HSCT.

Nine patients relapsed during a follow-up of 3 to 8 months, and 10 patients proceeded to HSCT. Two relapses occurred after HSCT, one in a patient who had CD19-negative blasts, and 7 relapses occurred without HSCT.

The overall survival rate at 6 months was 57%, and the median survival was 8.5 months.

For those patients who had a transplant after CAR therapy, the median survival was 10.8 months, and the survival rate at 6 months was 68%.

Dr Park pointed out that maximum T-cell expansion occurred between days 7 and 14 and correlated with the occurrence of cytokine release syndrome (CRS). The T cells persisted for 1 to 3 months following infusion.

The main adverse events were those associated with CRS and neurologic changes. Severe CRS requiring vasopressors or mechanical ventilation occurred in 5 patients (18%) overall and in 5 patients (33%) with morphologic disease before therapy. Severe CRS did not occur in any patient with minimal disease before therapy.

Grade 3 or 4 neurotoxicity occurred in 7 patients (25%) overall, in 6 patients (40%) with morphologic disease, and in 1 with minimal disease (8%) before therapy.

The investigators observed no graft-vs-host disease exacerbation, and CRS was managed with an IL-6R inhibitor, steroids, or both.

Dr Park noted that the neurologic symptoms are reversible and can occur independently of CRS.

He also pointed out that CR rates were similar regardless of different disease risk factors, and that durable responses have been achieved in patients who did not have a subsequent HSCT.

*Information in the abstract differs from that presented at the meeting.

CAR produces durable responses in B-cell ALL