T-cell therapy shows antitumor activity for advanced myxoid/round cell liposarcoma
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CHICAGO — A single infusion of letetresgene autoleucel demonstrated antitumor activity among patients with advanced or metastatic myxoid/round cell liposarcoma, results from a pilot study suggested.
Data from the trial’s primary analysis — presented at ASCO Annual Meeting — showed superior efficacy outcomes among patients who received standard lymphodepletion before treatment with the investigational T-cell receptor (TCR) therapy.
Background
Treatment of myxoid/round cell liposarcoma typically starts with surgical resection followed by adjuvant chemotherapy or radiation.
Many patients will develop recurrent or metastatic disease and be offered one of multiple standard chemotherapy regimens — typically anthracycline-based therapy — according to Sandra P. D'Angelo, MD, medical oncologist at Memorial Sloan Kettering Cancer Center.
“These therapies produce reasonable response rates and good disease control but —unfortunately — none of these chemotherapy agents are likely to cure patients with recurrent and metastatic disease, highlighting the rationale to explore new and novel therapeutics,” D’Angelo told Healio.
Letetresgene autoleucel (Adaptimmune/GlaxoSmithKline), often called lete-cel, is an autologous T-cell therapy that is genetically altered to express a TCR that recognizes the cancer testis antigen NY-ESO-1 bound to HLA-A*02 on the surface of cancer cells.
The idea to evaluate lete-cel in patients with myxoid/round cell liposarcoma came from a previous clinical trial that used the investigational therapy for synovial sarcoma — another malignancy that expresses high levels of the NY-ESO-1 antigen, D’Angelo said.
“Our experience in synovial sarcoma demonstrated that using a T-cell therapy that targets this antigen leads to a promising response rate of 50%, with a median progression-free survival of 15 months and overall survival of 24 months,” she said. “All of that encouraging clinical data in patients with synovial sarcoma prompted exploration of lete-cel in myxoid/round cell liposarcoma.”
Methodology
D’Angelo and colleagues enrolled 23 patients (median age, 47 years; range, 33-72) with histologically confirmed, HLA-matched advanced metastatic or inoperable high-grade myxoid/round cell liposarcoma, 20 of whom subsequently received a single infusion of lete-cel. Sixty percent of patients received at least two previous lines of therapy.
Researchers divided study participants into two cohorts. One group received reduced-dose lymphodepletion (n = 10) and the other received standard-dose lymphodepletion (n = 10) prior to lete-cel infusion.
Objective response rate served as the study’s primary endpoint. Other endpoints included safety, duration of response and PFS.
Median follow-up was 5.6 months for the reduced-lymphodepletion group and 12.9 months in the standard lymphodepletion group.
Key findings
The efficacy analysis showed an ORR of 20% in the reduced lymphodepletion group compared with 40% in the standard lymphodepletion group.
The investigators noted a median duration of response of 5.3 months (95% CI, 1.9-8.7) in the reduced lymphodepletion group compared with 7.5 months (95% CI, 6-not estimable) among those who received standard lymphodepletion.
Patients who received reduced lymphodepletion had a median PFS of 5.4 months (95% CI, 2-11.5) compared with 8.7 months (95% CI, 0.9-not estimable) in the standard lymphodepletion group.
Most patients (80%) experienced cytokine release syndrome, with a quarter of patients having grade 3 or higher. Researchers reported no cases of graft-versus-host disease, neurotoxicity or Guillain-Barré syndrome.
Grade 3 or higher treatment-related neutropenia occurred in 90% of patients.
Clinical implications
Use of lete-cel led to clinically meaningful responses for patients regardless of whether they received standard or reduced-dose lymphodepletion, D’Angelo said. However, she added, the results of this study indicate that standard lymphodepletion prior to T-cell infusion leads to higher response rates.
“With only 10 patients in each cohort, we have to be mindful of the small sample size and the clear need to further study,” she told Healio. “Nevertheless, the responses appear promising and form the basis for additional study in larger cohorts.”
D’Angelo said further evaluation of lete-cel is underway as part of the IGNYTE-ESO trial, which is enrolling a cohort of patients with myxoid/round cell liposarcoma who will receive the TCR therapy after standard-dose lymphodepletion.
“Current standard chemotherapy is an effective way to initially treat patients who have recurrent myxoid/round cell liposarcoma, but its overall lack of durability makes it an unlikely cure for most patients,” D’Angelo said. “Having the opportunity to offer an infusion of lete-cel — with the prospect of a durable response and disease control without any further intervention — holds promise for these patients.”
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D'Angelo SP, et al. Abstract 11500. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
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