[HTML][HTML] Pomalidomide for symptomatic Kaposi's sarcoma in people with and without HIV infection: a phase I/II study
MN Polizzotto, TS Uldrick, KM Wyvill… - Journal of Clinical …, 2016 - ncbi.nlm.nih.gov
Journal of Clinical Oncology, 2016•ncbi.nlm.nih.gov
Purpose Kaposi's sarcoma (KS) is a multicentric tumor caused by Kaposi's sarcoma–
associated herpesvirus. Unmet needs include therapies that are oral, anthracycline sparing,
and deliverable in resource-limited settings. We evaluated pomalidomide, an oral immune
modulatory agent, in patients with symptomatic KS. Methods The primary objectives were to
assess tolerability, pharmacokinetics, and activity. Initial dosage level was 5 mg once per
day for 21 days per 28-day cycle, with a de-escalated level of 3 mg if not tolerable, and …
associated herpesvirus. Unmet needs include therapies that are oral, anthracycline sparing,
and deliverable in resource-limited settings. We evaluated pomalidomide, an oral immune
modulatory agent, in patients with symptomatic KS. Methods The primary objectives were to
assess tolerability, pharmacokinetics, and activity. Initial dosage level was 5 mg once per
day for 21 days per 28-day cycle, with a de-escalated level of 3 mg if not tolerable, and …
Abstract
Purpose
Kaposi's sarcoma (KS) is a multicentric tumor caused by Kaposi's sarcoma–associated herpesvirus. Unmet needs include therapies that are oral, anthracycline sparing, and deliverable in resource-limited settings. We evaluated pomalidomide, an oral immune modulatory agent, in patients with symptomatic KS.
Methods
The primary objectives were to assess tolerability, pharmacokinetics, and activity. Initial dosage level was 5 mg once per day for 21 days per 28-day cycle, with a de-escalated level of 3 mg if not tolerable, and aspirin 81 mg once per day thromboprophylaxis. HIV-infected patients required controlled viremia with either persistent KS despite 3 months of antiretroviral therapy (ART) or progressive KS despite 2 months of ART. Evaluations included tumor response and health-related quality of life (HRQL).
Results
Twenty-two patients were treated; 15 (68%) were HIV infected, 17 (77%) had advanced (T1) disease, and 19 (86%) previous KS therapy excluding ART. All were treated with 5 mg because no dose-limiting toxicities occurred. Over 156 cycles, the grade 3/4 adverse events possibly attributable to therapy were neutropenia (23 cycles, 10 patients), infection (1 cycle), and edema (1 cycle). Sixteen patients responded (73%; 95% CI, 50% to 89%): nine of 15 HIV-infected patients (60%; 95% CI, 32% to 84%) and all seven HIV-uninfected patients (100%; 95% CI, 59% to 100%). Median time to response was 4 weeks (range, 4 to 36 weeks). HRQL showed no impairment during therapy and improved satisfaction with appearance at end therapy (P=. 03). Significant increases in CD4+ and CD8+ cells were seen in patients with and without HIV, together with a transient increase in Kaposi's sarcoma–associated herpesvirus viral load at week 4 (P=. 05).
Conclusion
Pomalidomide is well tolerated and active in KS regardless of HIV status. Responses were rapid, with improved self-reported outcomes, and occurred in advanced and heavily pretreated disease. Correlative studies support, at least in part, an immunologic mechanism of activity.
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