A phase I trial of pomalidomide in combination with liposomal doxorubicin in patients with Kaposi sarcoma with or without other KSHV-associated diseases

11552 Background: Kaposi sarcoma herpesvirus (KSHV, also known as human herpesvirus 8 [HHV-8]), is the causative agent of Kaposi sarcoma (KS), a multicentric angioproliferative tumor, a form of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). KS can be difficult to treat when it occurs with KSHV-MCD or KICS; resulting in high mortality rates. Liposomal doxorubicin (LD) is an FDA-approved treatment for KS. Pomalidomide, an oral immunomodulatory drug, is safe and has demonstrated activity in KS, but the activity of the combination (pomalidomide+LD) in KS alone or with KSHV-associated diseases is unknown. Methods: The primary objective was to evaluate safety and tolerability of pomalidomide+LD in two groups of patients with KS requiring systemic therapy: Group I (GI)- KS alone; Group II (GII)- KS with concurrent KSHV-MCD or KICS. Patients received LD at 20 mg/m2 intravenously on day 1 of a 28-day cycle combined with pomalidomide once daily on days 1 to 21 at escalating dose levels (DL) (I - 2mg, II - 3mg, or III- 4mg) in a 3+3 design until plateau of response or other pre-specified criteria. Patients received 81mg of aspirin daily as thromboprophylaxis. KS responses were evaluated using the modified AIDS Clinical Trial Group criteria. Results: Thirty-four cisgender men, all with T1-stage KS [21 patients (62%) in GI and 13 patients (38%) in GII] were treated; 32 (94%) were HIV-infected and 22 (65%) had prior chemotherapy for KS (15/21 GI and 7/13 GII). There were no dose-limiting toxicities (DLTs) at DLIII for GI, and additional patients were treated at DLIII. In GII, grade 3 rash and pharyngeal edema were DLTs observed at 3mg of pomalidomide. Overall a median of 6 cycles were administered; the most common grade 3/4 toxicity was neutropenia. Among evaluable patients receiving >2 cycles,17/21 patients in GI had a response (all partial) (81% [95% confidence interval (CI) 58-95%]) and 5/10 patients in GII had a response (4 partial and 1 complete) (50% [95% CI 19-81%]). Conclusions: Pomalidomide+LD was well-tolerated and active in heavily pretreated patients with KS alone. In patients with KS and other KSHV-associated diseases, activity was noted but less well-tolerated. Clinical trial information: NCT02659930 .