Abstract Body

Background: Kaposi sarcoma (KS) is a multicentric tumor caused by human herpesvirus 8 and remarkable for its responsiveness to patient immune status. Unmet clinical needs include agents that are oral, anthracycline-sparing, and deliverable in resource limited settings. We evaluated pomalidomide, an oral immunomodulatory agent, in symptomatic KS.

Methods: We performed a prospective phase I/II study to assess the tolerability and pharmacokinetics (PK) of pomalidomide and its anti-tumor activity at the tolerable dose. Primary dose level was 5mg 21 days per 28 day cycle, with a de-escalated level of 3mg if this was not tolerable, and aspirin 81 mg daily as thromboprophylaxis. HIV-infected patients (pts) were eligible if they had controlled viremia and either persistent KS despite 3 months antiretroviral therapy (ART) or progressive KS despite 2 months ART. Evaluations included PK day 1 and 15 cycle 1; KS response by ACTG criteria each cycle; and health related quality of life (HRQL) by FAHI end cycle 3 and end therapy. Study registration NCT1495598.

Results: Primary enrollment completed with 22 pts. All were men; 15 (68%) HIV-infected; med age 50 years (range 32-74); advanced disease (T1) in 16 (72%); prior systemic therapy other than ART in 18 (82%). In HIV-infected, med CD4 429 (135-874); time on ART 48 months (7-227); all HIV VL <50 copies/mL.
No dose limiting toxicities occurred at 5mg and this dose was taken to phase II; all pts were treated at 5mg. Of 148 cycles, grade 3/4 adverse events at least possibly attributable to therapy were: neutropenia (23 cycles [c], 10 pts); CD4 lymphopenia (2 c, 1 pt); and peripheral edema (1 c, 1 pt). Other cytopenias, constipation, rash, and fatigue were common but mild.
15 pts had objective responses (preliminary overall rate 68%, 95% CI 45.1-86.1%): 4 complete (18%) 11 partial (PR, 50%); 4 stable disease (SD, 18%) and 3 progression (13%). 1 pt with SD and 2 with PR continue to improve on therapy. Median time to response 4 weeks (4-36). HRQL showed improved satisfaction with appearance at end therapy (p=0.01), and no impairment during therapy.
PK showed T½ 7.1±2.5 hrs, CMAX 61.2±29.3 ng/mL, AUCLAST 624.4±448.4, consistent with prior estimates, no accumulation and no difference by HIV status or ART type.

Conclusions: Pomalidomide is well tolerated and active in KS regardless of HIV status. Responses were rapid, linked to improved self reported outcomes, and occurred even in advanced and heavily pre-treated KS. Further development could address important unmet needs.

Waterfall plots show maximal change in the number of nodular lesions (left) and total lesions (right) during therapy for each patient.