A phase 1 study of interleukin-15 in combination with mogamulizumab in relapsed and refractory T-cell malignancies
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Gordon, Max J., Sigrid Dubois, Milos D. Miljkovic, et al. “A Phase 1 Study of Interleukin-15 in Combination with Mogamulizumab in Relapsed and Refractory T-Cell Malignancies.” Blood Neoplasia 2, no. 1 (2024): 100054. https://doi.org/10.1016/j.bneo.2024.100054.
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This work was written as part of one of the author's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.
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Abstract
Recombinant human interleukin-15 (rhIL-15) is an immunotherapeutic agent that enhances natural killer (NK) cells to augment the antibody-dependent cellular cytotoxicity (ADCC) of monoclonal antibodies. Mogamulizumab is a CC chemokine receptor 4–directed monoclonal antibody that exerts cytotoxicity through ADCC and depletes regulatory T cells within the tumor microenvironment. We conducted a phase 1 clinical trial of rhIL-15 in combination with mogamulizumab. Patients with relapsed or refractory adult T-cell leukemia/lymphoma (ATLL), mycosis fungoides (MF), and Sezary syndrome (SS) received a fixed dose mogamulizumab, combined with escalating doses of rhIL-15 to identify the maximum tolerated dose (MTD). Six patients were enrolled, 4 with ATLL and 2 with MF/SS. The most common adverse events were rash, infection, and fever (67% of all). Two patients (33%) had grade 4 acute kidney injury, and in 25% of cycles, grade 3 or higher anemia was present. The MTD was dose level 1. One patient with ATLL had a partial response despite receiving only 4 cycles because of grade 4 myositis. Circulating NK cells were increased in all patients during the first cycle and a rapid reduction in tumor cells within the peripheral circulation was noted. Ex vivo assessment demonstrated increased NK cell activation and increased cell lysis in the presence of monoclonal antibodies after only 5 days. Our small study suggests that rhIL-15, in combination with mogamulizumab, leads to effector NK cell activation and regulatory T-cell depletion but has an unfavorable safety profile. Future development of combinations of immunotherapy that target the microenvironment in relapsed or refractory T-cell lymphomas remains rational. This trial was registered at www.ClinicalTrials.gov as #NCT04185220.