ASH: Gilead's CAR-T Yescarta holds up in more first-line lymphoma patients as part of earlier use push
With the cell therapy field largely pivoting to the next generation of those drugs, established players like Gilead’s Kite and Bristol Myers Squibb are still carving away at new routes into earlier lines of care. This weekend, Kite churned out more data for its CAR-T Yescarta in first-line lymphoma patients as part of a hopeful push for a greater market share.
In updated results from the Phase II ZUMA-12 study, Yescarta posted a 78% complete response rate among 37 patients with high-risk large B cell lymphoma at a median follow-up of just shy of 16 months, the drugmakers said Monday at #ASH21.
These single-arm, open-label data follow results presented at last year’s ASH showing a 73% complete response rate in 27 patients and offer some proof of Yescarta’s lasting durability in high-risk LBCL patients, most of whom eventually relapse after first-line standard of care, Kite said.
All median survival checkpoints hadn’t been reached at a median 15.9 months after infusion, but Kite floated 12-month outcomes estimates of 81% for durable responders, 73% for event-free survival, 75% for progression-free survival and 91% for patients still alive.
ZUMA-12 is part of Gilead’s push into earlier lines of therapy for Yescarta beyond its current approvals in third-line-or-later blood cancer. Also this week, Kite read out more data from the Phase III ZUMA-7 study showing Yescarta significantly beat out standard-of-care in second-line LBCL patients as part of a head-to-head challenge there.
According to Frank Neumann, Kite’s global head of clinical development, Yescarta’s promising efficacy in first-line patients could prove attractive to physicians looking for better options than the chemotherapy regimen R-CHOP, the longtime standard of this care in this setting that some patients either cannot tolerate or does not stop relapse in many patients.
This study enrolled a group of patients Kite defined as high-risk with a rare genetic arrangement known as double- or triple-hit lymphoma with a high prognostic score on a commonly used metric known as IPI, as well as a positive PET following two cycles of treatment with a CD20-targeted antibody and anthracycline regimen. Patients were eligible for bridging chemotherapy before their one-time infusion.
With the rise of genetic biomarker testing, companies are getting a better look earlier at which patients might be at higher risk of relapse and thus in greater need of early intervention from non-conventional therapies. In Kite’s case, that high-risk group is evolving as early testing evolves, but Neumann said the company’s work in late-line patients offers a pretty clear path forward in at least that one specific standard for patients.
“This field is evolving — if you look at the multiple myeloma space (for example), if you ask two physicians on either side of the Atlantic what a high-risk patient is, you’ll get two different responses,” Neumann said. “We have the tremendous advantage of having treated so many patients, and their clinical course and their translational biomarker data is something that we can leverage and that we are learning from, and that defines the approach that the medical field thinks is a high-risk population.”
The big question in taking current-generation cell therapies into earlier lines of care is a well-established safety profile that includes high risk of cytokine release syndrome and neurological toxicity. In this study, Grade 3 or higher CRS occurred in 8% of patients and 23% of patients experienced a Grade 3 or higher neurological event. There were no deaths tied to treatment with Yescarta although one patient died from Covid-19. All but one CRS and neurological events were resolved through treatment by the data cutoff.