Axicabtagene Ciloleucel Improves Outcomes in Relapsed/Refractory Follicular Lymphoma

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Data from a comparative analysis of the ZUMA-5 (NCT03105336) and SCHOLAR-5 trials suggest that treatment with axicabtagene ciloleucel (Yescarta) induced substantial improvements in objective response rate (ORR), progression-free survival (PFS), time to next treatment (TTNT) and overall survival (OS) in patients with relapsed/refractory follicular lymphoma (R/R FL) compared with currently available therapies. These findings were presented at the 2021 European Hematology Association (EHA) Virtual Conference.¹

“Follicular lymphoma is one of the most common non-Hodgkin lymphomas, and patients can experience frequent relapses, which quickly leaves us short of treatment options,” said study author John Gribben, MD, DSc, FRCP, professor, medical oncology, Cancer Research UK Barts Centre, London, UK, in a statement.² “We are very encouraged by these data that suggest a significant and sustained survival benefit with Yescarta even after multiple rounds of prior treatment.”

Researchers sought to compare outcomes from an updated 18-month analysis of the ZUMA-5 trial to a matched sample of patients from the SCHOLAR-5 external control cohort. They analyzed 85 patients from the SCHOLAR-5 cohort, and 86 patients from ZUMA-5.

Patients included in this study had to have grade 1-2 R/R FL and have failed 2 or more previous lines of treatment as well as have an ECOG score of 0 or 1. After propensity score weighting, baseline characteristics in ZUMA-5 included a median age of 62 years (range, 34-79 years), 48 males (55.8%), 49 patients whose disease progressed within 24 months of first-line chemoimmunotherapy [POD24] (57%), 3.6 prior lines of treatment, 63 patients refractory to prior line (73.3%), 21 patients with a prior SCT (24.4%), 8.44 months since time of last treatment, 76.05 months since diagnosis, 51 patients with ECOG score of 0 (59.3%) and 35 patients with an ECOG score of 1 (40.7%).

READ MORE: Cilta-Cel Demonstrates Durable Responses at 18 Months in Relapsed/Refractory Multiple Myeloma

In SCHOLAR-5, the baseline characteristics included a median age of 61 years(range, 36-89 years), 53 males (61.9%), 47 POD24 patients (55.9%), 3.53 prior lines of treatment, 65 patients refractory to prior line of treatment (76.6%), 24 patients with a prior SCT (28%), 7.74 months since time of last treatment, 82.24 months since diagnosis, 21 patients with an ECOG score of 0 (29%) and 51 patients with an ECOG score of 1 (71%).

ORR among the patient population was substantially higher in the ZUMA-5 trial (94.2%) than in the SCHOLAR-5 trial (49.9%; OR = 16.24; 95% CI, 5.63-46.85; P < .0001). Moreover, complete responses were significantly improved in the ZUMA-5 cohort (79.1%) than in the SCHOLAR-5 cohort (29.9%; OR = 8.86; 95% CI, 4.3-18.25; P < .0001).

“ORR, [complete response], PFS and TTNT comparisons showed statistically significant improvements highlighting deep and durable treatment effect of axi-cel in this patient population,” Gribben said during his presentation.

A median PFS was not reached in the cohort from ZUMA-5, whereas it was 12.68 months in the SCHOLAR-5 cohort (P < .001). Additionally, a median OS was not reached in the ZUMA-5 cohort; however, median OS in the SCHOLAR-5 cohort was 59.8 months (P = .0125).

“The substantial overall survival benefit seen in this study suggest that axi-cel addresses an important unmet medical need for relapsed/refractory follicular lymphoma patients,” said Gribben.

Median TTNT also significantly favored the ZUMA-5 cohort (not reached) over the SCHOLAR-5 cohort (14.43 months) (P < .001).

Of note, neither a median OS, PFS or TTNT were met in a primary and subgroup analysis of ZUMA-5.

“This data certainly supports that axi-cel represents a significant improvement in treatment options for patients with relapsed/refractory follicular lymphoma,” Gribben concluded.

Based on findings from the phase 2 ZUMA-5 trial, the FDA approved axi-cel for the treatment of this patient population in March 2021.

REFERENCES

1. Ghione P, Patel A, Bobillo, S, et al. A comparison of clinical outcomes from ZUMA-5 (axicabtagene ciloleucel) and the international SCHOLAR-5 external control cohort in relapsed/refractory follicular lymphoma (R/R FL). Presented at: 2021 European Hematology Association Congress; June 9-17; Virtual. Abstract LB1904.
2. Longer-term data for Kite’s Yescarta® in relapsed or refractory follicular lymphoma demonstrate substantial survival improvement over current therapies in comparative analysis. News release. Kite. June 12, 2021. https://www.kitepharma.com/news/press-releases/2021/6/longer-term-data-for-kites-yescarta-in-relapsed-or-refractory-follicular-lymphoma-demonstrate-substantial-survival-improvement-over-current-therapie