Patients with relapsed or refractory (r/r) follicular lymphoma live longer when they are treated with the novel anti-CD19 chimeric antigen receptor T-cell therapy axicabtagene ciloleucel (axi-cel; Yescarta) than when they are treated with other current therapies, suggests a new analysis.
The new results for overall survival with axi-cel come from the ZUMA-5 study. Those results were compared with data from an international cohort of similar patients who received current therapies.
“The substantial overall survival benefit seen in this study suggests that axi-cel addresses an important unmet medical need or r/r follicular lymphoma patients,” commented first author John G. Gribben, DSc. “These data support that axi-cel represents a significant improvement in treatment options for patients with r/r follicular lymphoma.”
Gribben is director of the Experimental Cancer Medicine Center and director of stem cell transplantation at Saint Bartholomew’s Hospital, Queen Mary’s School of Medicine, accutane oregon University of London, United Kingdom.
He is also the current president of the European Hematology Association. He was presenting the new findings in a late-breaker abstracts session at the virtual European Hematology Association (EHA) 2021 Annual Meeting.
Commenting on the study, Kirsten Gronbaek, MD, a professor of hematology at Rigshospitalet, in Copenhagen, Denmark, and co-moderator of the EHA session, said the study’s findings are encouraging.
“I think these are very impressive results that give new hope for patients with relapsed/refractory follicular lymphoma,”she told Medscape Medical News.
Axi-cel was recently approved by the US Food and Drug Administration for the treatment of adult patients with r/r follicular lymphoma after receiving two or more lines of systemic therapy. This approval in March 2021 was based on data from this ZUMA-5 trial.
The product was already on the market, having first been approved in 2017 for the treatment of large B-cell lymphoma in patients who experience disease progression after receiving two previous lines of therapy. That approval was based on the results from the ZUMA-1 pivotal trial.
Updated Results on R/R Follicular Lymphoma
ZUMA-5 was a pivotal trial that showed for the first time that CAR T-cell therapy yielded a high response rate (94%) in r/r indolent non-Hodgkin lymphoma and a 12-month overall survival rate of 92.9%.
At the EHA meeting, Gribben and colleagues reported updated results from ZUMA-5.
They compared these results to results from a matched sample of patients with r/r follicular lymphoma in the international SCHOLAR-5 external control cohort who met the ZUMA-5 eligibility requirements and were treated in the real-world setting with currently available therapies.
In the propensity-matched groups, there were 86 patients with r/r follicular lymphoma in the ZUMA-5 cohort. (median follow-up, 23.3 months) and 85 patients in the SCHOLAR cohort (median follow-up, of 26.2 months).
The groups were matched and balanced at baseline with regard to age, sex, having received at least two prior lines of therapy, having undergone prior stem cell therapy, and other factors.
Treatments received in the SCHOLAR cohort were wide ranging and included stem cell transplant, anti-CD20-chemotherapy combinations, and other chemotherapy. Patients were also included from Gilead’s Delta trial of idelalisib (n = 25).
“What was clear to us is the treatment of relapsed/refractory follicular lymphoma is extremely heterogeneous in clinical practice, and this highlights the lack of uniform treatment options for these patients,” Gribben said.
He added that “experimental treatment options were commonly used in late-line follicular lymphoma treatment.”
Among the patients in both studies who were treated with at least two prior lines of therapy, the overall response rate was substantially higher in the ZUMA-5 trial, at 94.2%, vs 49.9% in the SCHOLAR cohort, for an odds ratio (OR) of 16.2 (P < .0001).
The complete response rates among those patients were 79.1% vs 29.9% (OR, 8.86; P < .0001).
Although the median rate of progression-free survival was not reached in the ZUMA-5 trial, in the SCHOLAR cohort, the rate was 12.7 months (hazard ratio [HR], 0.30; P < .001).
Importantly, the median overall survival was not reached in ZUMA-5 and was 59.8 months with the SCHOLAR cohort (HR, 0.42; P = .0125).
The median time to next treatment was significantly longer in the ZUMA-5 trial (not reached) in comparison with SCHOLAR-5 (14.43; HR, 0.42; P < .001).
Similar responses were observed in all outcomes among patients who had received three or more prior lines of therapy.
“After applying a propensity score method, axi-cel demonstrated a substantial improvement in all clinical endpoints in the ZUMA-5 clinical trial when compared to SCHOLAR-5, and these findings were maintained across the prespecified sensitivity analyses,” Gribben said.
“The overall response rate, complete remission, progression-free survival, and time-to-next-treatment comparisons showed statistically significant improvements, highlighting the deep and durable treatment effect of axi-cel in this patient population,” he added.
Unique Study Design
In further comments, Gronbaek said that the study is notable for its use of the international cohort instead of a traditional randomized trial design.
“This is a very interesting approach, and as we gather more and more data, for instance, in the HARMONY Alliance projects…this may offer even better opportunities to identify matching controls in the future. It will also be interesting when patients can be matched according to molecular features in the future,” Gronbaek said.
The study was supported by Kite, a Gilead company. Gribben reported relationships with Kite, Janssen, Bristol-Myers Squibb, AstraZeneca, AbbVie, Morphosys, Novartis, Takeda. and TG Therapeutics. Gronbaek has disclosed no relevant financial relationships..
European Hematology Association (EHA) 2021 Annual Meeting: Abstract S130. Presented June 11, 2021.
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