Responses to CAR T-cell therapy deepen over time for lymphoma
CHICAGO — Complete response rates to axicabtagene ciloleucel among patients with refractory large B-cell lymphoma increased through long-term follow-up of the ZUMA-1 trial, according to study data presented at the ASCO Annual Meeting.
Some patients with initial partial responses developed complete responses as late as 1 year following treatment, suggesting response to therapy deepens over time.
“Over half of the patients who progress will have progressed before 3 months after treatment,” Frederick Lundry Locke, MD, program co-leader of immunology at Moffitt Cancer Center, told HemOnc Today. “We did an analysis of the ZUMA-1 trial to figure out what to do with patients at 3 months. If we have a patient in remission at 3 months — whether it be a partial or a complete response — can we wait it out? Or, do we need to deliver chemotherapy or transplantation? We found that over 80% of patients, whether they are in partial or complete response at 3 months, remained in remission 1 year after the therapy, which is pretty remarkable.”
Earlier results from ZUMA-1 showed axicabtagene ciloleucel (Yescarta; Kite Pharma, Gilead) — an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy — induced significant clinical benefit with a manageable safety profile for patients with refractory large B-cell lymphoma. As HemOnc Today previously reported, these data led to the therapy’s FDA approval as the second-ever approved CAR T-cell product.
Locke and colleagues conducted extended follow-up of the ZUMA-1 trial after a median of 15.4 months.
The analysis included 108 patients with refractory B-cell lymphoma who received low-dose conditioning followed by 2 x 106 CAR T cells/kg.
The best objective response rate remained consistent at 82% from the primary analysis — which occurred after a median of 8.7 months — and at long-term follow-up. Fifty-eight percent of patients achieved complete response.
Forty-two percent of patients had ongoing responses, including 40% with complete response.
Median OS was not reached, and 60% of patients achieved 12-month OS.
“These clinical results compare very favorably to robust historical controls, which suggest that this same set of patients would at best expect a 25% chance of having a response to another therapy besides CAR T cells,” Locke said during his presentation.
Twelve percent of patients experienced grade 3 or worse cytokine release syndrome, and 31% of patients experienced grade 3 or worse neurologic events.
Overall median duration of response was 11.1 months (95% CI, 3.9-not reached).
Locke and colleagues then evaluated the time to response for patients with an objective response and a complete response, and they assessed partial and complete response at month 3 as a prognostic factor for PFS.
“One-third of patients in complete response initially attained a partial response, and that response deepened over time,” Locke said. “Over half of patients who progressed did so by the 3-month time point, leading to the need to define treatment practices at this time. We believe month 3 is clinically relevant to understand patient outcomes.”
Overall, time to response among the 84 responders was “quite rapid,” Locke said, occurring at a median of 1 month.
Forty-one percent of patients with a partial response converted to a complete response, and this conversion occurred as late as 12 months after a single infusion of CAR T-cell therapy.
Landmark PFS analyses showed that most of the 60 patients who achieved stable disease or better at 3 months had prolonged disease control, with a corresponding 12-month PFS rate of 73%.
Twelve-month PFS rates reached 79% among 42 patients with complete response at 3 months and 78% among nine patients with partial response at 3 months.
“If I have a patient I am going to treat with CAR T cells, I will tell them that the 3-month time point is really important,” Locke told HemOnc Today. “We will wait to see how they are doing at 3 months and, if they are in remission, that is good news, because it means they have a very high likelihood of sustaining that response for at least 1 year without an additional therapy, just a single infusion of CAR T cells.
“We do not need to give additional chemotherapy or stem cell transplant.” Locke added. “This answers a big question about whether we should be consolidating with transplant. I would not want to give additional therapy to this patient. It would be better to ride it out and see how things go.” – by Alexandra Todak
Locke FL, et al. Abstract 3003. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Kite Pharma supported this trial. Locke reports honoraria from Kite Pharma; a consultant/advisory role with Cellular Biomedicine Group; research funding from FORMA Therapeutics and Kite Pharma; and a patent for the survivin vaccine. Please see the abstract for all other authors’ relevant financial disclosures.