Update reveals ongoing responses in ZUMA-1

Furthermore, the investigators observed no differences in patients who received tocilizumab or corticosteroids.

The median duration of response for all patients was 11.1 months. For those who achieved CR, the median duration of response has not yet been reached.

Three of the 7 patients (43%) in the phase 1 part of the trial had an ongoing CR at 24 months.

At the median follow-up of 15.4 months, 42% of patients were progression-free, and 56% were alive.

The median overall survival has not been reached. Investigators estimated the 18-month overall survival to be 52%.

Safety

Adverse events (AEs) of grade 3 or higher occurred in 97% of patients, and serious AEs of grade 3 or higher occurred in 46% of patients in the updated analysis.

No new axi-cel-related AEs of cytokine release syndrome, neurologic events, or grade 5 AEs have arisen since the primary analysis.

There were four grade 5 events, 2 of which were related to axi-cel.

“All these four grade 5 events were previously reported—three in the phase 2 and one in the phase 1 trial,” Dr Neelapu said.

Most patients experienced hypogammaglobulinemia and B-cell aplasia. Eight percent of patients had IVIG support during the study.

Infections, such as pneumonia, influenza, and viral infection, were the most common new-onset treatment-emergent serious AEs occurring after 6 months in 10 patients. All were manageable and resolved prior to the data cut-off.

Persistence and resistance

“We observed long-term persistence of the CAR T cells,” Dr Neelapu said.

CAR T cells persisted in 71% of patients still responding at 1 year. And durable responses were observed in patients with and without detectable CAR T cells.

A central review committee analyzed biopsies of 21 evaluable patients at progression to try to determine the mechanism of resistance.

Fourteen of 21 (67%) biopsies were CD19-positive. Of these, 9 were PD-L1-positive, 4 were PD-L1-negative, and 1 was not evaluable.

Seven patients (33%) were CD19-negative compared to baseline. Of these, 4 were PD-L1-positive, 2 were PD-L1-negative, and 1 was not evaluable.

“This PD-L1 expression was observed in both CD19-positive relapses and CD19-negative relapses,” Dr Neelapu emphasized.

Of the 21 patients, 62% were PD-L1-positive.

Investigators hypothesize that 2 potential mechanisms could contribute to relapse: loss of CD19 and expression of PD-L1.

Axi-cel (Yescarta™) was approved by the US Food and Drug Administration in October for the treatment of adults with relapsed or refractory large B-cell lymphoma.