AMC-070: Lenalidomide Is Safe and Effective in HIV-Associated Kaposi Sarcoma

Autor: Erin G, Reid, Kelly, Shimabukuro, Page, Moore, Richard F, Ambinder, Jack D, Bui, Semi, Han, Otoniel, Martínez-Maza, Dirk P, Dittmer, David, Aboulafia, Elizabeth Yu, Chiao, Toby, Maurer, Robert, Baiocchi, Ronald, Mitsuyasu, William, Wachsman
Rok vydání: 2022
Předmět:
Zdroj: Clinical Cancer Research. 28:2646-2656
ISSN: 1557-3265
1078-0432
Popis: Purpose:Kaposi sarcoma (KS), an endothelial cell tumor associated with KS herpesvirus (KSHV), remains among the most common malignancies occurring with HIV infection (HIV-KS). As an oral anti-inflammatory, antiangiogenic, and immunomodulatory agent, lenalidomide is potentially an attractive alternative to standard chemotherapy for KS.Experimental Design:The primary objectives of this phase I/II trial were to determine the maximum tolerated dose (MTD) and response rates for lenalidomide in HIV-KS. Secondary objectives included correlating response with natural killer (NK) and T-cell subsets, plasma cytokines, viral copy number, and KSHV gene expression in biopsies. Four dose levels of oral lenalidomide taken 21 consecutive days of 28-day cycles were evaluated in adults with HIV-KS on antiretroviral therapy with controlled viremia.Results:Fifteen and 23 participants enrolled in phases I and II, respectively, 76% of whom had received prior KS therapy. The MTD was not reached, declaring 25 mg as the recommended phase II dose (RP2D). The most frequent adverse events were neutropenia, fatigue, leukopenia, and diarrhea. Of the 25 evaluable participants receiving RP2D, 60% responded. Correlative studies performed in a subset of participants demonstrated a significant increase in proportions of blood T cells with T-regulatory phenotype, and plasma cytokines trended toward a less inflammatory pattern. Clinical response was associated with loss of KSHV transcription.Conclusions:Lenalidomide is active in HIV-KS. The most common adverse events were manageable. With 60% of participants receiving RP2D obtaining a partial response and See related commentary by Henry and Maki, p. 2485
Databáze: OpenAIRE
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