CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

Session O-7 Oral Abstracts

Room 613

10:00 am– 12:15 pm KS and Cervical/Anal Dysplasia: Tale of 2 Tumors and TB and Other OIs 87 Pomalidomide for Kaposi Sarcoma in PeopleWith andWithout HIV: A Phase I/II Study Mark N. Polizzotto 1 ;Thomas S. Uldrick 1 ; Kathleen M.Wyvill 1 ; Karen Aleman 1 ; Margaret Bevans 2 ; Cody Peer 1 ; Douglas Figg 1 ; Seth Steinberg 1 ; Jerome B. Zeldis 5 ; RobertYarchoan 1 1 National Cancer Institute (NCI), Bethesda, MD, US; 2 National Institutes of Health (NIH), Bethesda, MD, US; 3 National Cancer Institute (NCI), Bethesda, MD, US; 4 National Cancer Institute (NCI), Bethesda, MD, US; 5 Celgene Corporation, Summit, NJ, US 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 T ½ 7.1 ± 2.5 hrs, C MAX 61.2 ± 29.3 ng/mL, AUC LAST 624.4 ± 448.4, consistent with prior estimates, no accumulation and no difference by HIV status or ART type.

Oral Abstracts

Waterfall plots showmaximal change in the number of nodular lesions (left) and total lesions (right) during therapy for each patient. 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. 88 Prognostic Model for Patients With Kaposi Sarcoma TreatedWith ART Alone in Africa Miriam O. Laker-Oketta 1 ; DavidV. Glidden 2 ;VictoriaWalusansa 1 ; Jackson Orem 1 ; A. Rain Mocello 2 ;Toby Maurer 2 ; PeterW. Hunt 2 ; Andrew D. Kambugu 1 ; Edward Mbidde 1 ; Jeffrey Martin 2 1 Makerere University College of Health Sciences, Kampala, Uganda; 2 University of California San Francisco, San Francisco, CA, US; 3 Makerere University College of Health Sciences, Kampala, Uganda; 4 University of California San Francisco (UCSF), San Francisco, CA, US; 5 University of California San Francisco (UCSF), San Francisco, CA, US Background: While patients with functionally disabling Kaposi’s sarcoma (KS) require chemotherapy for rapid reduction in tumor burden, the management of KS which lacks functionally disabling complications is less certain. This is particularly true in sub-Saharan Africa, where the relative high cost of chemotherapy makes decisions about its use difficult and the use of antiretroviral therapy (ART) alone common as initial KS treatment. However, because a substantial fraction of patients with KS in Africa who are treated with ART alone fare poorly, it would be useful to be able to predict which patients with KS will do well on ART alone versus those who might benefit from additional interventions. Methods: We studied HIV-infected adults in Uganda with KS with no functionally disabling complications who were initially treated with ART alone as part of the AntiRetrovirals for KS (ARKS) trial. We evaluated the predictive value of 57 variables regarding clinical history, physical exam, laboratory characterization, and radiographic findings, each measured prior to ART. The outcome was death or KS progression necessitating chemotherapy. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to identify variables with the highest predictive accuracy upon cross-validation. Results: Among 224 subjects, 44%were women, and median values prior to ART initiation were: 34 years old, 119 CD4+ T cells/mm 3 , and 5.3 log 10 copies/ml of plasma HIV RNA. The final prediction model had 3 variables: number of anatomic sites with KS, hemoglobin, and Karnofsky performance score. The model showed adequate discrimination: area under the ROC curve = 0.84 (95% CI: 0.78-0.90), and at an optimal cutpoint, the sensitivity for predicting poor outcome was 88% and specificity 74%. Calibration was also good

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CROI 2015