Second-Line Axi-Cel Bests Standard in Relapsed/Refractory Large B-Cell Lymphoma

— The CAR T-cell therapy ended in tremendously longer total survival

by
Mike Bassett, Workers Creator, MedPage These days
June 5, 2023

CHICAGO — Sufferers treated with the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel; Yescarta) in the 2nd line for early relapsed or refractory trim B-cell lymphoma had tremendously longer total survival (OS) than these treated with identical old care, according to an diagnosis of the ZUMA-7 trial.

At a median apply-up of 47.2 months amongst 359 patients, median OS changed into once no longer reached in the axi-cel community (95% CI 28.6 months to no longer estimable) versus 31.1 months (95% CI 17.1-no longer estimable) in the extraordinary-care community (HR for death 0.73, 95% CI 0.54-0.98, P=0.03), reported Jason Westin, MD, of the University of Texas MD Anderson Most cancers Center in Houston, at the American Society of Scientific Oncology (ASCO) annual assembly.

The findings were additionally published in the Novel England Journal of Pills.

The estimated 4-year OS price changed into once 54.6% (95% CI 47.0-61.6) with axi-cel and 46.0% (95% CI 38.4-Fifty three.2) with identical old care consisting of chemotherapy and stem-cell transplantation for patients who replied to chemotherapy.

Westin emphasized that the 27% low cost in the risk of death with axi-cel changed into once finished despite the true fact that 57% of patients in the extraordinary-0f-care arm got subsequent third-line cellular immunotherapy, including CAR T-cell therapy, off protocol.

“With a median apply-up of 47.2 months, these worn survival recordsdata are per healing therapy,” Westin said. “To our recordsdata, ZUMA-7 is the first randomized trial in any most cancers to imprint an total survival income for a CAR T-cell therapy over gift identical old of care. And right here is the first trial in virtually 30 years to tremendously give a boost to total survival in the 2nd-line atmosphere for patients with trim B-cell lymphoma who find healing-intent therapy.”

“Taken together, ZUMA-7 confirms axi-cel is a 2nd-line identical old of affection patients with refractory or early relapsed B-cell lymphoma, based fully on superior total survival,” he added.

ASCO-invited discussant Asher Alban Akmal Chanan-Khan, MD, of the Mayo Health middle in Jacksonville, Florida, identified that “giving CAR-T earlier in the therapy paradigm is seemingly a better preference for our patients.”

He agreed that ZUMA-7 “must alter the most contemporary identical old of care, making CAR-T, or axi-cel, based fully on the recordsdata we possess, most smartly-preferred 2nd-line therapy in relapsed/refractory trim B-cell lymphoma.”

Westin and colleagues additionally reported that the investigator-assessed median progression-free survival (PFS) changed into once 14.7 months (95% CI 5.4-43.5) with axi-cel versus 3.7 months (95% CI 2.9-5.3) with identical old care (HR 0.51, 95% CI 0.38-0.67). The estimated 4-year PFS charges were 41.8% (95% CI 34.1-49.2) and 24.4% (95% CI 17.2-32.2), respectively.

The median investigator-assessed tournament-free survival (EFS) changed into once 10.8 months (95% CI 5.0-25.5) with axi-cel and a pair of.3 months (95% CI 1.7-3.1) with identical old care, and the estimated 4-year EFS charges were 38.9% and 17.3%, respectively (HR 0.42, 95% CI 0.33-0.55).

An earlier diagnosis of the trial’s main outcome (EFS according to central overview) showed that at a median apply-up of 24.9 months, median EFS changed into once 8.3 months in the axi-cel community and a pair of.0 months in the extraordinary-care community, with 24-month EFS charges of 41% and 16%, respectively. In 2022, ZUMA-7 recordsdata convinced the FDA to present axi-cel the inexperienced light in adult patients with trim B-cell lymphoma that’s refractory to first-line chemoimmunotherapy or relapses interior twelve months of first-line chemoimmunotherapy.

As for security, Westin reported that cytokine free up syndrome, as anticipated, changed into every other time identical old in the axi-cel arm (events of any grade: 92%; grade ≥3: 6%) as were neurologic events (grade ≥3: 92% vs 1% with identical old care).

Hypogammaglobulinemia changed into once reported in 11.2% of the patients in the axi-cel community, and prolonged hypogammaglobulinemia (≥6 months after the axi-cel infusion) changed into once reported in 5.9%. Grade ≥3 prolonged cytopenia (≥6 months after the initiation of definitive therapy) changed into once reported in 4.7% of patients in the axi-cel community.

Infections of any grade were reported in 44.7% in the axi-cel community and 31.5% in the extraordinary-care community, whereas grade ≥3 infections were reported in 16.5% and 11.9%, respectively.

ZUMA-7 changed into once performed at 77 websites worldwide. Eligible patients had histologically confirmed trim B-cell lymphoma that changed into once refractory to first-line therapy or that had relapsed from total remission no more than twelve months after the completion of first-line chemoimmunotherapy, including an anti-CD20 monoclonal antibody and an anthracycline-containing routine.

Sufferers had a median age of 59, with 30% 65 and older. Seventy-four percent of patients had main refractory disease, 45% had a high 2nd-line age-adjusted World Prognostic Index (2 or 3 risk factors), 54% had an elevated lactate dehydrogenase degree, 79% had stage III or IV disease, and 19% had high-grade B-cell lymphoma.