Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study

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 17 (77%) 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.

Cerebellar Tumor Extension as a Late Event of Long-standing, Supratentorial Low-grade Gliomas: Case Report

OBJECTIVE AND IMPORTANCE: Nonpilocytic low-grade glial tumors in adults occur mostly in the supratentorial compartment. However, a few cases of infratentorial low-grade gliomas (LGG) have been described. The occurrence of LGG in the cerebellum in the setting of a previously existing supratentorial glioma is rare. CLINICAL PRESENTATION: We present three young patients with a histologically confirmed diagnosis of long-standing supratentorial LGG. All three patients presented years after their initial diagnosis with a second, nonenhancing lesion in the cerebellum, compatible with the radiological appearance of LGG. Two patients subsequently became symptomatic from these lesions and underwent surgical resection of the cerebellar lesions that were found to have similar pathological features to the original supratentorial tumors. This was confirmed by histology (both patients) and genetic markers (one patient). INTERVENTION: Magnetic resonance imaging did not demonstrate tumor continuity between the supratentorial and infratentorial lesions in any of the patients. The third patient has shown no cerebellar symptoms to date and is only followed with periodic magnetic resonance imaging. CONCLUSION: The anatomic/pathological basis of these rare cases may include a primary, multicentric tumor formation, or a secondary tumor infiltration of the cerebrocerebellar pathways, leading to the formation of the cerebellar tumor.