Retreatment with CAR-T therapy shows clinical efficacy in lymphoma
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In a small sample, retreatment of patients with large B-cell lymphoma showed good response, notably in patients who had complete response on initial treatment, according to a poster presented at ASCO 2020 Virtual Scientific Program.
“While [axicabtagene ciloleucel] has demonstrated durable responses in a subset of patients, approximately half of all responders relapse and little is known about the efficacy of retreatment with CAR T-cell therapy,” Frederick L. Locke, MD, co-leader of the Immunology Program at Moffitt Cancer Center in Tampla, Florida, said in his recorded presentation.
Locke presented a continuation of ZUMA-1, multicenter phase 1/2 study looking at axicabtagene ciloleucel (axi-cel, Yescarta, Kite) in which four cohorts (n = 14) received retreatment with axi-cel after lympho-depleting chemotherapy. In their first treatment, 93% of patients responded to the regimen, with a median treatment response of 3.3 months.
“Response to retreatment was more common among patients who achieved complete response with first treatment compared with partial response or stable disease,” Locke said. “While six out of seven patients who achieved complete response with first treatment responded after retreatment, only two out of the other seven patients achieved a response with retreatment.”
The objective response rate with retreatment was 57%, he said, and median duration of response was 9.4 months, though he noted this time included ongoing response after consolidating transplant for four of the patients.
Locke reported the severity and incidence of neurologic events were lower with retreatment than initial treatment (79% vs. 57% incidence). Rates of cytokine release syndrome (CRS) were similar at 93% in initial treatment vs. 86% in retreatment. Locke showed that CAR T-cell expansion was lower after retreatment compared with complete response in initial treatment and that was paralleled by lower tumor burden levels at retreatment. They observed lower levels of key cytokines as well. Interferon gamma, IL-15 and IL-6 were all lower with retreatment.
“Based on this limited sample size, retreatment with axi-cel may have clinical efficacy in some patients with large B-cell lymphoma, especially patients who achieve complete response with their first treatment,” Locke said. “CAR T-cell expansion, serum cytokine levels and severe CRS and neurologic events appear to be attenuated at retreatment and durability of response remains to be determined as several patients receive consolidating allogeneic transplant.”
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Locke F, et al. Abstract 8012. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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