Michael Crump, MD

Michael Crump, MD, of the Division of Medical Oncology and Hematology at Princess Margaret Cancer Centre, Toronto, expressed some concerns about the study presented by Shadman et al in patients with large B-cell lymphoma (LBCL).

“These data should be interpreted with caution. The patient populations in the two groups being compared in this abstract are not the same. They likely have inherent differences in disease biology that have not been accounted for that could explain the apparent reported treatment effect,” he told The ASCO Post.

This concern is illustrated by the higher proportion of patients in the group receiving chimeric antigen receptor (CAR) T-cell therapy who had recognized adverse prognostic factors, such as elevated lactate dehydrogenase levels (37% vs 31%), primary refractory diffuse LBCL (29% vs 20%), early treatment failure (72% vs 58%), and, importantly, more lines of prior therapy (3 vs 2), he noted. “Previous studies have demonstrated inferior outcomes in patients with chemotherapy-sensitive diffuse LBCL who received three prior lines of chemotherapy vs two lines before autologous stem cell transplantation (ASCT), emphasizing the importance of unmeasured confounders affecting the outcomes of patients in retrospective analyses,” Dr. Crump commented.

Data From Other Trials

“The data reported for patients with early failure after first-line therapy are comparable to those reported in the SCHOLAR-1 analysis,¹ where patients with complete response by computed tomography scan after salvage therapy who underwent ASCT had favorable outcomes despite having primary refractory disease or early disease progression. However, the randomized ZUMA-7 trial² reported an improvement in overall survival for second-line CD19 CAR T-cell therapy compared with a standard salvage therapy approach followed by ASCT,” he said.

“These results bring into question the appropriateness of suggesting deferral of CAR T-cell therapy to the third line, hypothesized by the authors to potentially provide equivalent patient benefit to second-line use for those with a complete response by [fluorine-18 fluorodeoxyglucose positron-emission tomography] after standard salvage therapy,” he continued.

“The data reported by Shadman et al highlight the ongoing need for additional prospective randomized trials of CAR T-cell therapy in patient populations where the benefit of this treatment remains uncertain. In light of the significant barriers to access to CAR T-cell therapy faced by patients and practitioners in many parts of the world, such studies to generate high-quality data to inform clinical decision-making remain a priority,” Dr. Crump stressed. 

DISCLOSURE: Dr. Crump reported no conflicts of interest.

REFERENCES

1. Crump M, Neelapu SS, Farooq U, et al: Outcomes in refractory diffuse large B-cell lymphoma: Results from the international SCHOLAR-1 study. Blood 130:1800-1808, 2017.

2. Westin JR, Oluwole OO, Kersten MJ, et al: Survival with axicabtagene ciloleucel in large B-cell lymphoma. N Engl J Med 389:148-157, 2023.