Response to Prior Therapy Predicts Outcomes With Axi-Cel in Refractory Large B-Cell Lymphoma

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February 9, 2021 - Patients with refractory large B-cell lymphoma have less to gain from axicabtagene ciloleucel if they have never achieved a complete response to any line of prior therapy.

Patients with refractory large B-cell lymphoma (LBCL) have less to gain from axicabtagene ciloleucel (axi-cel; Yescarta) if they have never achieved a complete response (CR) to any line of prior therapy, according to a single-center retrospective analysis led by Sairah Ahmed, MD, and Paolo Strati, MD, at The University of Texas MD Anderson Cancer Center.¹

The analysis comprised 171 patients with LBCL treated with axi-cel at the academic center between January 2018 and April 2020. At a median follow-up of 9 months, the median progression-free survival (PFS) was 6 months (95% CI, 4-8) in patients who never attained a CR to prior therapy. There was a trend toward shorter PFS in the group that never attained a CR compared with patients who achieved a CR with any prior line of therapy (5 vs 26 months, respectively; P = .10).

The data were presented virtually during the 2021 Transplantation & Cellular Therapy Meetings.

“In our large cohort, we identified lack of prior complete response to any line of therapy to predict for inferior outcomes with axi-cel CAR T-cell therapy,” the investigators noted in their poster. “Despite CAR T-cell therapy having a non-overlapping mechanisms with standard cytotoxic chemotherapy, it appears that disease refractoriness may be therapy agnostic.”

Additional data showed that the median overall survival (OS) showed a similar trend to median PFS. Median OS was not reached in the cohort without a prior CR. However, the 1-year OS rate was shorter at 60% in this group versus those who attain a CR to a prior treatment, at 75%, although the difference missed statistical significance (P = .07).

Axi-cel is currently approved for the treatment of patients with diffuse large B-cell lymphoma, transformed follicular lymphoma, and high-grade B-cell lymphoma after at least 2 lines of systemic therapy. In the phase 2 portion of the ZUMA-1 trial,² which was the basis for the approval in this setting, there was no significant difference in outcomes in patients with refractory LBCL based on prior lines of treatment, noted the researchers.

“Beyond tumor volume, there is a lack of data in predicting response outcomes,” they wrote.

Of the 171 patients who received axi-cel as standard of care as part of the analysis, 134 did not attain a CR to any prior line of therapy and 37 did achieve a CR.

There was no statistically significant difference in age, gender, histology, ECOG performance status, stage, or International Prognostic Index (IPI) between the 2 groups at baseline. The median age of the overall cohort was 59 years (range, 18-85), 70% were male, 82% had Ann Arbor stage III or IV LBCL, 64% had more than 1 extra-nodal site, 56% had an IPI score of 3 to 5. The median level of lactate dehydrogenase at baseline was 323 U/L. The median number of prior therapies was 4 (range, 2-15). About one-fourth (n = 45; 26%) had received previous autologous stem cell transplant (SCT) and 3 (2%) received prior allogeneic SCT. Fifty percent had bridging therapy, including 30% with chemotherapy as a bridge, 12% with radiation therapy, and 8% with biologic therapy.

The need for bridging therapy, which was 54% in those never attaining a CR versus 35% in those who attained a CR to prior therapy (P = .04), and lack of prior autologous SCT (22% vs 43%, respectively; P = .01) were identified as significant factors associated with lack of a CR to prior therapy.

The findings from this analysis should be explored in larger registry studies and targeted in future clinical trials, the authors concluded.

In September 2020, a supplemental biologics license application was filed with the FDA for axi-cel for the treatment of patients with relapsed/refractory follicular lymphoma and marginal zone lymphoma following 2 or more previous lines of systemic treatment.

References

Ahmed S, Strati P, Fayad LE, et al. Efficacy of chimeric antigen receptor (CAR) T-cell therapy, axicabtagene ciloleucel (axi-cel), in patients with refractory large B-cell lymphoma (LBCL). Presented at: 2021 Transplantation & Cellular Therapy Meetings; February 8-12, 2021; Virtual. Abstract 493.
Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-Cell lymphoma. N Engl J Med. 2017;377(26):2531-2544. doi: 10.1056/NEJMoa1707447