The U.S. Food and Drug Administration (FDA) has approved axicabtagene ciloleucel (Yescarta), a CAR T-cell therapy, for the treatment of adult patients with relapsed or refractory large B-cell lymphoma.

Large B-cell lymphoma is a rare cancer and the most common non-Hodgkin lymphoma. Approximately 30-40% of patients with this rare blood cancer will need second-line treatment, as their cancer will either relapse or become refractory to first-line treatment.

The FDA approval of axicabtagene ciloleucel is largely based on results from the ZUMA-7 study (NCT03391466), a randomized, open-label, phase 3 study evaluating the safety and efficacy of axicabtagene ciloleucel compared to current standard of care for second-line therapy (platinum-based salvage combination chemoimmunotherapy regimen followed by high-dose therapy [HDT] and ASCT in those who respond to salvage chemotherapy) in adult patients with relapsed or refractory large B-cell lymphoma within 12 months of first-line therapy.

The primary endpoint was event-free survival (EFS), defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause.

Persons given axicabtagene ciloleucel demonstrated a four-fold improvement in median EFS (8.3 months vs. 2.0 months) compared to those given SOC (P <.0001). The treatment group also showed a 2.5-fold increase in the number of patients who were alive after two years and did not experience cancer progression or require the need for additional cancer treatment (40.5% vs. 16.3%).

Additionally, more patients responded to axicabtagene ciloleucel (ORR: 83% vs. 50%, p<0.0001) and achieved a complete response (CR) with axicabtagene ciloleucel (CR rate: 65% vs. 32%) compared to standard of care.

Finally, in the ZUMA-7 trial, axicabtagene ciloleucel had a safety profile consistent with previous studies. Among the 168 axicabtagene ciloleucel-treated patients evaluable for safety, Grade ≥3 cytokine release syndrome and neurologic events were observed in 7% and 25% of patients, respectively. In the SOC arm, 83% of patients had high grade events, mostly cytopenias.

In a news release, Frederick Lick, MD of the Moffitt Cancer Center, and Principal Investigator of the ZUMA-7 study noted, “Today’s approval marks an exciting new standard of care. The ZUMA-7 trial enabled us to look at the broader picture of what happens to patients after a decision is made to follow a particular treatment path. What we found was that axi-cel resulted in three times as many patients receiving treatment with curative intent (CAR T-cell therapy), and an overall better outcome for patients than the previous standard of care. Additionally, we have now amassed significant experience with CAR T-cell therapy to better manage or prevent side-effects, making this treatment more accessible for older patients and those with medical conditions for whom the standard of care might be difficult.”

The drug does come with a Black Box Warning for possible cytokine release syndrome and neurologic toxicities, and is only available under a Risk Evaluation and Mitigation Strategy (REMS).

To learn more about large B-cell lymphoma and other rare cancers, visit https://checkrare.com/diseases/cancers/