FDA Approves Axi-cel in Second Line for LBCL, Expands CAR T Pool by 11,000 in US Alone

The expanded use of axi-cel, sold as Yescarta, while not unexpected, nonetheless represents uncharted territory in cancer care.

The FDA today authorized the use of Kite Pharma’s axicabtagene ciloleucel (axi-cel) for patients who have relapsed just once from large B-cell lymphoma (LBCL), a change that could expand the pool of patients eligible for chimeric antigen receptor (CAR) T-cell therapy by 11,000 just in the United States. This change will expand use of a high-cost cancer treatment from the sickest patients to those who are comparatively fit, raising new questions for payers and policy makers.

“Kite started with a very bold goal: creating the hope of survival through cell therapy,” Christi Shaw, CEO of Kite Pharma, said in a statement. “Today’s FDA approval brings that hope to more patients by enabling the power of CAR T-cell therapy to be used earlier in the treatment journey. This milestone has been years in the making. On behalf of the entire Kite community, we would like to thank the patients and physicians who have been on this journey with us.”

The expanded use of axi-cel, sold as Yescarta, while not unexpected, nonetheless represents uncharted territory in cancer care at a time when clinicians are highlighting problems with utilization management. However, Lori Ann Leslie, MD, director of indolent lymphoma and chronic lymphocytic leukemia research programs at John Theurer Cancer Center, said the approval may allow some of her patients to start the CAR T-cell therapy process as early as next week.

“I’ve talked to a few of my patients about the pending approval, and how treatment landscapes are evolving,” Leslie said in an interview. “Once we see the label, we’ll see—it may be very relevant for them.”

The approval is based data from ZUMA-7, which showed that patients treated with axi-cel were 2.5 times more likely to be alive after 2 years without the need for additional treatment than those who received standard of care (40.5% vs 16.3%). In addition, data published in October 2021 show that patients in ZUMA-1, which led to the original approval, had a 2-year survival rate of 54% compared with 20% for patients enrolled in SCHOLAR-1, which was a retrospective study of similar patients treated with salvage chemotherapy.

During his presentation at the 2021 meeting of the American Society of Hematology (ASH), Moffitt Cancer Center’s Frederick Locke, MD, highlighted a key point: Of the patients randomized to axi-cel, 94% successfully received CAR T-cell treatment; in comparison, only 36% of those randomized to standard of care received high-dose therapy and autologous stem-cell therapy (ASCT).

The question will be whether the payer infrastructure can manage a wave of new patients seeking treatment with axi-cel, including some who conceivably could be treated with the existing standard of care, which is high-dose therapy followed by ASCT. Payer delays in approving axi-cel could make this expensive treatment less effective once it reaches patients, and it could force clinicians to order rounds of chemotherapy to stabilize patients during the manufacturing process, adding to costs.

This is an important consideration for the health system: Many patients with LBCL who prepare for stem-cell transplant never get to that point, while most patients in the ZUMA-7 trial who were screened for CAR T-cell therapy were able to receive treatment.

Leslie said this aspect of ASCT is “devastating” for patients who cannot make it to transplant. When patients cannot achieve a complete response to their salvage chemotherapy, having an option such as CAR T-cell therapy, “Where the cells are living, active drugs—there’s really no benefit of going to transplant.”

“I was very reassured by seeing those numbers in ZUMA-7, because that’s what we see in practice,” Leslie said. Patients who don’t do well with high-dose chemotherapy and transplant represent an area of unmet need, and the approval will change the treatment paradigm “pretty immediately.”

For their part, Kite Pharma officials said previously they have done their homework—they will use the same network of 112 authorized centers to administer the treatments that they’ve been using since axi-cel was first approved in 2017. That approval was for patients who whose LBCL had returned or failed to respond to at least 2 systemic treatments, a much smaller group of patients. Kite officials say the process to secure payer approval for CAR T-cell therapy has greatly improved since that time.

Cost is a major consideration for payers. Axi-cel treatments have been listed at $373,000 and that does not include the cost of hospitalization or treatment of adverse events, which can include cytokine release syndrome (CRS). Over time, management of CRS has vastly improved.

In a January interview, Kite officials told Evidence-Based Oncology™, a publication of The American Journal of Managed Care®, that last year’s quick addition of a new CAR T-cell therapy for mantle cell lymphoma to most health plans was a strong sign that the axi-cel indication will be embraced. Based on the recent experience at her institution, Leslie anticipates a smooth launch, especially since this will be a new indication, not a brand new therapy.

Kite has invested $85 million in a new manufacturing facility in suburban Maryland that will offer a speedy turnaround for the customized treatments, which start with a patient’s own T cells and make personalized therapies that are infused back into each patient. Based on results presented at ASH, that tight turnaround matters. The lead investigator for a competitor whose key trial failed to match axi-cel’s results attributed the difference, in part, to the fact that the average time from removal of T cells to infusion was 27 days for axi-cel compared with 52 for the other treatment, tisagenlecleucel (tisa-cel, Kymriah; Novartis).