Clinical Pearls & Morning Reports
Published February 16, 2022
Locke et al. conducted ZUMA-7, an international, randomized, phase 3 trial that compared axicabtagene ciloleucel (axi-cel) with standard care as second-line treatment in patients with early relapsed or refractory large B-cell lymphoma. Read the NEJM Original Article here.
Q: Why are novel second-line treatments needed for relapsed or refractory large B-cell lymphoma?
A: Standard-care second-line treatment in the curative setting for patients with relapsed or refractory large B-cell lymphoma is high-dose chemotherapy with autologous stem-cell transplantation if the disease is responsive to salvage chemoimmunotherapy. Patients whose disease does not respond to salvage chemotherapy and those who are not considered to be candidates for high-dose chemotherapy with autologous stem-cell transplantation have poor outcomes. These patients may benefit from second-line therapies that have different mechanisms of action.
Q: Is axi-cel approved for use in patients with relapsed or refractory large B-cell lymphoma?
A: The autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy axi-cel is approved for the treatment of patients with relapsed or refractory large B-cell lymphoma who have received at least two previous systemic therapies. In the ZUMA-1 trial, which involved patients with refractory large B-cell lymphoma treated with axi-cel, 83% of the patients had a response and 58% had a complete response; the median overall survival was 25.8 months, and the 5-year overall survival was 43%.
A: Locke et al. observed a clear improvement with axi-cel, as compared with standard care, in event-free survival and the percentage of patients with a response. Axi-cel therapy was superior to standard care with a median event-free survival that was longer by a factor of more than 4, a 2-year event-free survival that was higher by a factor of 2.5, a significantly higher percentage of patients with a response, and double the percentage of patients with a complete response. Treatment with axi-cel also led to longer event-free survival than standard care across key subgroups, including patients with high-risk features, such as high-grade B-cell lymphoma (including double- or triple-hit lymphomas) and an age of 65 years or more, although further improvements in these subgroups are needed. The difference in overall survival between the two groups did not reach statistical significance.
A: Cytokine release syndrome occurred in 157 patients (92%) who received axi-cel, with an event of grade 3 or higher occurring in 11 patients (6%). No deaths related to cytokine release syndrome occurred. In the safety population, tocilizumab was administered to 65% of the patients, glucocorticoids to 24%, and vasopressors to 6%. The median cumulative use of tocilizumab, regardless of indication, was 1396 mg (range, 430 to 7200). The median time to the onset of cytokine release syndrome was 3 days (range, 1 to 10) after the infusion, and the median duration was 7 days (range, 2 to 43). All the events resolved.