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Background: Although immunotherapy has emerged as a therapeutic strategy for many cancers, there are limited studies establishing the safety and efficacy in people living with HIV (PLWH) and cancer. Methods: PLWH and solid tumors or Kaposi sarcoma (KS) receiving antiretroviral therapy and a suppressed HIV viral load received nivolumab at 3 mg/kg every 2 weeks, in two dose deescalation cohorts stratified by CD4 count (stratum 1: CD4 count > 200/µL and stratum 2: CD4 count 100–199/µL). An expansion cohort of 24 participants with a CD4 count > 200/µL was then enrolled. Results: A total of 36 PLWH received nivolumab, including 15 with KS and 21 with a variety of other solid tumors. None of the first 12 participants had dose‐limiting toxicity in both CD4 strata, and five patients (14%) overall had grade 3 or higher immune related adverse events. Objective partial response occurred in nine PLWH and cancer (25%), including in six of 15 with KS (40%; 95% CI, 16.3–64.7). The median duration of response was 9.0 months overall and 12.5 months in KS. Responses were observed regardless of PDL1 expression. There were no significant changes in CD4 count or HIV viral load. Conclusions: Nivolumab has a safety profile in PLWH similar to HIV‐negative subjects with cancer, and also efficacy in KS. Plasma HIV remained suppressed and CD4 counts remained stable during treatment and antiretroviral therapy, indicating no adverse impact on immune function. Trial Registration: ClinicalTrials.gov Identifier: NCT02408861. The anti‐PD1 inhibitor nivolumab may be used safely for treatment of cancer, and has activity in Kaposi sarcoma, in people living with HIV receiving antiretroviral therapy, a suppressed HIV viral load, and CD4 lymphocyte count of at least 100/µL. [ABSTRACT FROM AUTHOR]

BACKGROUND Myc-positive B-cell non-Hodgkin lymphoma (NHL) with or without a B-cell chronic lymphocytic leukemia/lymphoma 2 ( BCL2) rearrangement is associated with inferior progression-free survival (PFS) and overall survival (OS). In this study, the authors reviewed the outcomes of patients with myc-positive and double-hit NHL at The Ohio State University. METHODS All patients who had non-Burkitt, aggressive B-cell NHL from 2008 to 2011 were assessed for the t(14;18) translocation and for v-myc avian myelocytomatosis viral oncogene homolog ( CMYC) rearrangements at diagnosis, and all myc-positive patients were included in the current analysis. Associations with clinical characteristics were described, and univariable and multivariable models were used to assess correlations between clinical variables and outcomes. RESULTS Of 49 myc-positive patients, 29 patients also had BCL2 rearrangements (double-hit NHL). No patients underwent autologous stem cell transplantation in first remission. For all myc-positive patients, the median PFS was 16.6 months, and the median OS was 37.7 months. For patients who had double-hit NHL, the median PFS was 8 months, and the median OS was 12.5 months; whereas the median PFS and OS were not reached for myc-positive patients. A complete response (CR) after front-line therapy, the presence of t(14;18), International Prognostic Index (IPI) group, and age were associated with PFS; whereas only the achievement of a CR and age >60 years were associated with OS in the multivariable setting. The median PFS was 3.3 months, and the median and OS was 7.0 months for patients who did not attain a CR; and the medians were not reached for patients who achieved a CR ( P < .00001). CONCLUSIONS The achievement of a CR with front-line therapy is associated with a prolonged PFS and OS in patients with myc-positive NHL, even after adjusting for type of initial therapy, histology, age, IPI, or the presence of a concurrent BCL2 translocation. Cancer 2014;120:1677-1685. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: In vitro studies in mantle cell lymphoma (MCL) cell lines and patient-derived cells have demonstrated synergistic apoptosis with combined rituximab and bortezomib (R-bortezomib) compared with single-agent bortezomib. Therefore, the authors of this report evaluated R-bortezomib in a preclinical model and in a phase 2 clinical trial. METHODS: A Hu-MCL-severe combined immunodeficiency (SCID) model engrafted with the Jeko cell line was treated with R-bortezomib, bortezomib, or rituximab. Twenty-five patients with relapsed follicular lymphoma (n = 11) and MCL (n = 14) received 375 mg/m² rituximab on Days 1 and 8 and 1.3 to 1.5 mg/m² bortezomib on Days 1, 4, 8, and 11 every 21 days for a median of 3 cycles (range, 1-5 cycles). RESULTS: R-bortezomib resulted in a statistically significant improvement in overall survival in Hu-MCL-SCID mice. In the clinical trial, the overall response rate was 40% in all 25 patients, 55% in patients with follicular lymphoma, and 29% in patients with MCL. The estimated 2-year progressionfree survival (PFS) rate was 24% (95% confidence interval [CI], 10%-53%) in all patients and 60% (95% CI, 20%-85%) in responding patients. Thirteen patients (52%) developed grade 3 neurotoxicity, which consisted of constipation/ ileus, sensory or motor neuropathy, or orthostatic hypotension. Patients who were heterozygous for the CD32a (Fcc receptor IIa) 131 histidine (H) to arginine (R) polymorphism had a significantly decreased PFS (P = .009) after R-bortezomib compared with HH and RR homozygotes. CONCLUSIONS: R-bortezomib had significant activity in patients with relapsed or refractory follicular lymphoma and MCL, although an unexpectedly high incidence of grade 3 neurologic toxicity was a potential limiting factor with this combination. [ABSTRACT FROM AUTHOR]