Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: The ZUMA-5 investigators report that over 90% of patients with relapsed or refractory indolent non-Hodgkin’s lymphoma (NHL) in their trial have responded to axicabtagene ciloleucel (axi-cel) treatment
The primary analysis of the phase II trial of the autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy were presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition by Caron Jacobson, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA.
At the time of reporting, the study had enrolled 124 patients with grade 1–3a follicular lymphoma (FL) and 22 patients with nodal or extranodal marginal zone lymphoma (MZL), all of whom had relapsed or refractory disease after receiving at least two lines of treatment (median, three), including anti-CD20 monoclonal antibody therapy plus an alkylating agent.
The majority of patients had stage III–IV disease, high tumour bulk, had progressed within 2 years of their initial chemoimmunotherapy and were refractory to their last treatment, Caron Jacobson said.
The participants underwent leukapheresis and conditioning therapy, consisting of cyclophosphamide and fludarabine, followed by a single axi-cel infusion of 2x106 CAR T cells/kg.
After a median 17.5 months of follow-up, the primary endpoint of objective response rate (ORR) was 92% among the 104 patients who were assessed for treatment efficacy, 76% of whom had a complete response.
The corresponding rates were 94% and 80% for the 84 FL patients who had been followed-up for at least 12 months and 85% and 60% for the 20 MZL patients with at least 1 month of follow-up.
The ORR was consistent among key subgroups, including in patients positive or negative for CD19 status, the presenter said.
At data cutoff, the median duration of response, progression-free survival and overall survival were unreached with 12-month rates of 71.7%, 73.7% and 92.9%, respectively. Among the FL cohort, 64% of patients had an ongoing response at cutoff and this was more likely in patients with a complete versus partial response (78 vs 17%).
Grade 3 and more severe adverse events occurred in 86% of the 141 patients including 85% of the FL and 95% of the MZL patients, most commonly neutropenia, decreased neutrophils and anaemia. In addition, 7% of the patients experienced grade 3 or more severe cytokine release syndrome (CRS) and 19% had neurological events (NE) at this grade.
All but one of the 119 CRS events and 81 of the 87 NE had resolved by time of data cutoff, the researchers say. Three deaths were reported, of which one case of multisystem organ failure following CRS was attributed to axi-cel treatment.
Of note, the median peak CAR T-cell level in the patients was 38 cells/µL, occurring after a median of 9 days. Among the efficacy-assessed patients, the median peak cell level was numerically higher, albeit not significantly, in those who had an ongoing response at 12 months, compared with those who had relapsed. Peak cell level in the FL cohort was significantly associated with an increased risk of grade 3 and more severe CRS and NE and a “similar trend” was found for the MZL patients.
Describing axi-cel as having “high rates of durable responses” and a safety profile that was “manageable and appeared favorable” for the FL patients, when compared with the ZUMA-1 findings for refractory large B-cell lymphoma, Caron Jacobson concluded: “Axi-cel may be a highly promising therapeutic approach for patients with [relapsed/refractory indolent] NHL.”
A second ZUMA-5 analysis was presented as a poster at ASH 2020 by Julio Chavez, from the H Lee Moffitt Cancer Center & Research Institute in Tampa, Florida USA, and co-authors who followed-up nine FL and two MZL patients who progressed after an initial complete (n=10) or partial response (n=1) to axi-cel.
Following a second round of conditioning and axi-cel therapy, 10 patients achieved a complete response and one patient a partial response, with responses ongoing after a median 2.3 months of follow-up.
“Comparable instances of CRS and NEs were observed with retreatment as with first treatment”, the researchers noted, with neither occurring at grade 3 or higher.
“Based on a limited sample, axi-cel retreatment exhibited high response rates in patients with [relapsed/refractory indolent] NHL”, said Julio Chavez et al.
“Similar safety profiles and CAR T cell expansion were observed at retreatment and first treatment, and a lower tumor burden was observed before retreatment than before first treatment”, they noted.
“Confirmatory analyses with more patients and longer follow-up are needed.”
Jacobson C, Chavez JC, Sehgal AR, et al. Primary analysis of ZUMA-5: A phase 2 study of axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). 2nd ASH Annual Meeting and Exposition; 5–8 December 2020 (Abstract 700).
Chavez JC, Jacobson CA, Sehgal AR, et al. Retreatment with axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory indolent non-Hodgkin lymphoma in ZUMA-5. 2nd ASH Annual Meeting and Exposition; 5–8 December 2020 (Abstract 2036).
medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature group