Study of CAR-T for patients with non-Hodgkin lymphoma, HIV yields 'reassuring' results
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NEW ORLEANS — Chimeric antigen receptor T cells demonstrated acceptable efficacy with no additional safety concerns when administered to patients with non-Hodgkin lymphoma and HIV, retrospective study results showed.
Data from an interim analysis of the AIDS Malignancy Consortium Study (AMC-113) — presented at ASH Annual Meeting and Exposition — suggested treatment is safe for patients with HIV despite concerns about how CAR T cells may negatively impact immune system function among immunocompromised patients, investigators noted.
“The outcomes — based on this preliminary data — appear to be equivalent to that reported in patients without HIV,” Stefan K. Barta, MD, associate professor of clinical medicine at Perelman School of Medicine at University of Pennsylvania and director of the T-cell lymphoma program at Abramson Cancer Center, told Healio. "These results are reassuring.”
Background
Despite declining rates of non-Hodgkin lymphoma among individuals with HIV, it remains the most common cancer-related death in this population, Barta said.
People with HIV have been excluded from participating in clinical trials for CAR T-cell therapies and do not qualify for commercial use of tisagenlecleucel (Kymriah, Novartis) — one of three FDA-approved CD19-directed CAR-Ts for non-Hodgkin lymphoma.
“Based on this, it is highly likely that [clinicians] are reluctant to offer this life-saving therapy to patients living with HIV,” Barta said. “Some insurance providers may decline authorization based on a lack of available data.”
AMC-113 is a collaboration between the AIDS Malignancy Consortium and Center for International Blood and Marrow Transplant Research (CIBMT) to provide more data about the safety and efficacy of CAR T cells in patients with HIV.
Methodology
At ASH, Barta and colleagues presented interim results of AMC-113.
The prospective analysis included outcomes data for 27 patients (median age, 55 years; range, 29-70; 81% men; 52% white; 30% Black; 11% Latino) with HIV who received CD19-directed CAR T-cell therapy for a B-cell lymphoid malignancy.
Investigators used registry data from the CIBMT on patients who met study criteria and received CD19-directed CAR-T after Aug. 30, 2017.
Approximately half (54%) of study participants received some type of bridging therapy.
All patients underwent preconditioning chemotherapy followed by a single infusion of a CD19-directed CAR-T. Most (96%) received axicabtagene ciloleucel (Yescarta; Kite Pharma/Gilead Sciences).
Treatment efficacy and safety served as the primary outcomes. Secondary outcomes included treatment durability and impact of CAR-T on HIV.
Median follow-up was 6 months (range, 1-13).
Key findings
The analysis included 19 evaluable patients.
Fourteen (74%) developed cytokine release syndrome, but researchers reported no cases of grade 3 or grade 4 CRS.
One patient experienced a grade 5 CRS event in conjunction with grade 5 bacterial sepsis.
Five patients (26%) developed immune effector cell-associated neurotoxicity syndrome. One had grade 2 symptoms, three had grade 3 symptoms, and one had grade 4 symptoms.
Ten patients (53%) achieved objective response to CD19-directed CAR-T, including eight (42%) who achieved complete response.
Investigators reported a 6-month PFS rate of 58% (95% CI, 34-80) and a 6-month OS rate of 63% (95% CI, 38-85%).
Two patients died of bacterial infection and seven died of disease progression.
Clinical implications
The overall response rate observed in this interim analysis is comparable to what has been seen in the real-world setting for patients without HIV who received CD19-directed CAR-T for non-Hodgkin lymphoma, Barta said.
The investigators intend to enroll up to 30 patients with more than 1 year of median follow-up before issuing a final analysis. They also hope to confirm the results through a prospective study (AMC-112).
Inclusion of a more representative proportion of Black and Latino patients as part of the study population — closer to the proportion of patients who have HIV in the U.S. — strengthened the current findings, Barta said.
"People with HIV and underrepresented minorities are often excluded or not included in clinical trials of innovative therapies,” Barta told Healio. “This is an issue that needs greater attention from regulatory authorities and those who conduct these clinical trials.”
The key take-home message from the results is the importance of including people with HIV and underrepresented minorities in CAR-T trials, Barta said.
"Although HIV-associated non-Hodgkin lymphoma has become rarer in the United States, it is still very common in middle income countries, and we will need to think of ways to make these therapies more available in [those locations],” he said.
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Barta SK, et al. Abstract 763. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
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