An open-label, randomized, multi-center study comparing the sequence of high dose aldesleukin (interleukin-2) and ipilimumab (yervoy) in patients with metastatic melanoma

Authors

Merve Hasanov, Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas Md Anderson Cancer Center, Houston, USA.
Denái R. Milton, Department of Biostatistics, The University of Texas Md Anderson Cancer Center, Houston, USA.
William H. Sharfman, Department of Medical Oncology and Dermatology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Lutherville, USA.
Bret Taback, Department of Surgery, Division of Breast Surgery, New York-Presbyterian/Columbia University Medical Center, New York, USA.
Lee D. Cranmer, University of Arizona Cancer Center, Tucson, Az, Usa. Present Affiliation and Contact: Division of Medical Oncology, Department of Medicine, University of Washington Medical Center, and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, USA.
Gregory A. Daniels, Division of Hematology-Oncology, University of California San Diego, La Jolla, USA.Follow
Lawrence Flaherty, Department of Hematology-Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, USA.
Sigrun Hallmeyer, Advocate Aurora HealthFollow
Mohammed Milhem, Section of Oncology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, USA.

Recommended Citation

Hasanov M, Milton DR, Sharfman WH, et al. An Open-Label, Randomized, Multi-Center Study Comparing the Sequence of High Dose Aldesleukin (Interleukin-2) and Ipilimumab (Yervoy) in Patients with Metastatic Melanoma. Oncoimmunology. 2021;10(1):1984059. Published 2021 Oct 9. doi:10.1080/2162402X.2021.1984059

Affiliations

Advocate Medical Group

Abstract

Combination immunotherapy with sequential administration may enhance metastatic melanoma (MM) patients with long-term disease control. High Dose Aldesleukin/Recombinant Interleukin-2 (HD rIL-2) and ipilimumab (IPI) offer complementary mechanisms against MM. This phase IV study assessed the sequenced use of HD rIL-2 and IPI in MM patients. Eligible Stage IV MM patients were randomized to treatment with either two courses of HD rIL-2(600,000 IU/kg) followed by four doses of IPI 3 mg/kg or vice-versa. The primary objective was to compare one-year overall survival (OS) with historical control (46%, Hodi et al., NEJM 2010). Secondary objectives were 1-year progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) profile. Evaluable Population (EP) included patients who received at least 50% of planned treatment with each drug. Thirteen and 16 patients were randomized to receive HD rIL-2 first, and IPI first, respectively. One-year OS rate was 75% for intention to treat population. Eighteen patients were included in EP, 8 in HD rIL-2, 10 in IPI first arm. In EP, 1-year OS, PFS and ORR rates were 87%, 68%, and 50%, respectively. The frequency of AEs was similar in both arms with 13 patients experiencing Grade 3 or higher AEs, 3 resulting in the end of study participation. There was one HD rIL-2-related death, from cerebral hemorrhage due to thrombocytopenia. In this study with small sample size, HD rIL-2 and IPI were safe to administer sequentially in MM patients and showed more than additive effects. 1-year OS was superior to that of IPI alone from historical studies.

Type

Article

PubMed ID

34650833