CAR-T safe, effective for adults with multiple myeloma and renal insufficiency
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Adults with advanced multiple myeloma and renal insufficiency treated with idecabtagene vicleucel achieved similar outcomes as those with normal renal function, according to retrospective study results.
A single dose of the chimeric antigen receptor T-cell therapy presents no additional risk for treatment-related toxicities among patients with renal insufficiency, findings presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR showed.
“Patients with multiple myeloma and renal impairment ... should not be denied this therapy,” Surbhi Sidana, MD, assistant professor of medicine and leader of the myeloma cellular immunotherapy program at Stanford University School of Medicine, told Healio. “All future trials of CAR T-cell therapy in multiple myeloma should include cohorts of patients with renal impairment because this is such an important patient population.”
Background
Renal insufficiency affects a significant proportion of patients with multiple myeloma, Sidana said. However, patients with multiple myeloma who have renal insufficiency typically been excluded from pivotal trials that led to FDA approval of commercially available CAR-T therapies.
Consequently, little is known about efficacy and safety of these therapies in this population, Sidana said.
“A majority of patients will have real impairment because of multiple myeloma at some point in their journey,” Sidana told Healio. “Because these patients have limited treatment options, many physicians have offered CAR T-cell therapy to patients with impaired renal function, so we wanted to look at the collective experience and establish the safety and efficacy of [idecabtagene vicleucel] in this population.”
Methodology
Idecabtagene vicleucel (Abecma; Bristol Myers Squibb, 2seventy bio) — often called ide-cel — is a B-cell maturation antigen-directed CAR T-cell therapy.
Sidana and colleagues conducted a multicenter retrospective study to evaluate the therapy for patients with multiple myeloma who had renal insufficiency.
Investigators defined renal insufficiency as creatinine clearance less than 50 mL/min at the time of CAR-T infusion. They defined severe renal insufficiency as creatinine clearance less than 30 mL/min or requiring hemodialysis.
The cohort included 211 patients treated at 11 of the 14 centers that participate in the U.S. Multiple Myeloma Cellular Therapy Consortium.
The analysis included 183 patients (median age, 63 years; 35% women;16 % Black) with normal renal function and 28 patients (median age, 69 years; 68% women; 21% Black) with renal insufficiency. Eleven patients had severe renal insufficiency, including one patient on hemodialysis.
All patients received lymphodepleting preconditioning therapy per their institution’s dosing guidelines. Eighty-two percent of patients with renal insufficiency received a reduced dose of fludarabine as part of their preconditioning therapy.
Median follow-up was 6 months.
Key findings
Investigators reported no significant differences in incidence of cytokine release syndrome (84% vs. 89%) or neurotoxicity (19% vs. 21%) between those with or without adequate renal function.
Patients with renal insufficiency had longer median hospital stays after CAR-T infusion (13 days vs. 9 days; P = .05).
Grade 3 or greater cytopenia occurred more frequently among those with renal insufficiency at day 30 after CAR-T infusion (86% vs. 55%, P = .001) and at day 90 after infusion (36% vs. 27%).
Researchers observed no significant changes in renal function after CAR-T for most patients. Two patients required new hemodialysis after CAR-T, including one patient who had normal renal function before infusion.
Three patients with severe renal insufficiency had their function improve to a creatinine clearance of 30-49 mL/min 30 days after CAR T-cell therapy.
Efficacy analysis showed no significant differences in response rates based on renal function.
Researchers reported a higher overall response rate (96% vs. 83%) and complete response rate (58% vs. 42%) among those with renal insufficiency.
Results showed comparable PFS between those with adequate renal function and those with renal insufficiency (median, 8.1 months vs. 6.5 months; (HR = 1.4; 95% CI, 0.7-2.7).
Clinical implications
The results demonstrate the feasibility of providing ide-cel to patients with multiple myeloma and renal insufficiency, Sidana said.
“When we look at causes of death across the two groups of patients, there was no increased signal for death among patients with renal impairment,” she told Healio. “There was no signal for worsening of renal function [among] patients with renal impairment, so I believe [ide-cel] is something we can safely offer to those with renal insufficiency.”
A prospective study is planned that will allow researchers to evaluate the safety and efficacy of a uniform dose reduction of fludarabine as part of preconditioning for patients with renal insufficiency, Sidana said.
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Sidana S, et al. Abstract 42. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, Feb. 15-19, 2023; Orlando.
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