Long-Term Axi-Cel Data ‘May Be Suggestive of a Cure’ in Patients With Large B-Cell Lymphoma

Long-term clinical trial data continues to support the use of axi-cel (axicabtagene ciloleucel) in treating patients with relapsed/refractory large B-cell lymphoma (LBCL), according to data presented at the 2022 Tandem Meeting.

Researchers presented five-year data from the phase 2 ZUMA-1 clinical trial, including the one- and two-year event-free survival findings.

“In this updated five-year analysis, axi-cel induced long-term (overall survival) ... among treated patients,” according to Dr. Caron A. Jacobson, the medical director of the Immune Effector Cell Therapy Program and senior physician at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School. She continued, “Between the four- and five-year analysis, the time to next therapy curve remains stable and 92% of patients remained alive without a need for subsequent therapy, which may be suggestive of a cure in these patients.”

Investigators reported a five-year overall survival rate of 42.6% following treatment with axi-cel. In the population of patients who experienced a complete response, the five-year overall survival rate was 64.4% and the median overall survival was not reached. Additionally, 63% of complete responders were alive at the five-year data cut off. At the four-year data cutoff, one patient died at month 63 and one experienced progressive disease at month 54.

To be considered for treatment, patients were required to have LBCL, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma or transformed follicular lymphoma. Patients were also required to have not responded to their last chemotherapeutic treatment or have relapsed 12 months or less following autologous stem cell transplant, which is a stem cell transplant using the patient’s own healthy cells. Treatment with a previous anti-CD20 monoclonal antibody and anthracycline was also necessary.

Those who underwent treatment received a conditioning regimen of cyclophosphamide and fludarabine for three days to get them ready for the main line of treatment. This was followed by axi-cel.

The main goal of the study was overall response rate with first response assessment four weeks following infusion. Key secondary end points included overall survival, safety and translational evaluations.

A total of 111 patients were enrolled on the study, eight of whom did not undergo treatment for one of the follow reasons: side effects (four patients), no measurable disease (two patients), death due to disease progression (one patient), and manufacturing failure (one patient); this left 103 patients to undergo conditioning. Of these patients, two were not treated due to side effects and death, respectively.

The data cutoff was Aug. 11, 2021 and the median follow-up was 63.1 months.

Additional findings from the trial highlighted a median time to next anticancer therapy of 8.7 months following infusion. A total of 34% of patients were alive at cutoff with no subsequent therapy or retreatment with axi-cel. Two patients who had prior progression underwent new anticancer therapy.

The five-year overall survival rates among those who had or had not experienced an event-free survival at month 12 were 5.3% vs 90.9%, respectively.

Events were classified as instances when the cancer recurred or became worse.

The median overall survival was 8.3 months among those who experienced an event and was not reached in those who did not experience an event. Additionally, the five-year overall survival rates among those who did or did not have an event at month 24 were 11.3% and 92.3%, respectively. Moreover, the median overall survival in both respective groups was 9.2 months and not reached.

Investigators also determined that early CAR-T cell expansion was associated with ongoing response at 60 months. The median peak CAR T levels appeared to be numerically higher in those who had an ongoing response at month 60 and lower in those who relapsed or did not respond to treatment. Similarly, another trend was observed in those who experienced CAR-T cell expansion by area under the curve from day 0 to 28.

A total of 58% of patients had died by the cutoff date. No new safety signals had been observed as of the five-year data cutoff, including serious side effects or secondary malignancies related to treatment.

Patients most commonly died due to progressive disease (45 patients), side effects (four patients), secondary malignancies (one patient) or other reasons (nine patients).

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