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This report examined the benefits and risks of palbociclib plus endocrine therapy (ET) in men with hormone receptor‒positive (HR+)/human epidermal growth factor receptor 2−negative (HER2−) metastatic breast cancer (MBC). Palbociclib was evaluated using three independent data sources: real‐world data from pharmacy and medical claims, a de‐identified real‐world data source derived from electronic health records (EHRs), and a global safety database. From medical and pharmacy records, 1,139 men with MBC were identified; in the first‐line setting, median duration of treatment was longer with palbociclib plus ET (n = 37, 8.5 months, 95% confidence interval (CI), 4.4‒13.0) than ET alone (n = 214, 4.3 months, 95% CI, 3.0‒5.7) and specifically, was longer with palbociclib plus letrozole (n = 26, 9.4 months, 95% CI, 4.4‒14.0) than letrozole alone (n = 63, 3.0 months, 95% CI, 1.8‒4.8). In the EHR‐derived database, 59 men received treatment for MBC; real‐world response across all lines of therapy in the metastatic setting was reported in 4 of 12 patients (33.3%) in the palbociclib plus ET group vs. 1 of 8 (12.5%) patients in the ET group. Review of the global safety database did not identify any new safety signals in palbociclib‐treated men. Real‐world data indicated that men with MBC benefit from palbociclib plus ET, with a safety profile consistent with previous observations in women with MBC. Collective data on palbociclib in women and men in this report, including clinical trial data, real‐world data, and a well‐established risk/benefit profile, led to US approval of an expansion of the palbociclib indication to include men with MBC. [ABSTRACT FROM AUTHOR]

Helper-dependent adenovirus (HD-Ad) vectors with all adenoviral genes deleted mediate very long-term expression of therapeutic transgenes in a variety of animal models of disease. These vectors are associated with reduced toxicity and improved safety relative to traditional early region 1 deletion first-generation Ad (FG-Ad) vectors. Many studies have clearly demonstrated that FG-Ad vectors induce innate and adaptive immune responses in vivo; however, a comprehensive analysis of host immune responses to HD-Ad vectors has not yet been performed. In DBA/2 mice, intravenous injection of HD-Ad vectors encoding LacZ (HD-AdLacZ) or a murine secreted alkaline phosphatase (HD-AdSEAP) induced an early expression of inflammatory cytokine and chemokine genes in the liver, including interferun-inducible protein 10, macrophage inflammatory protein 2, and tumor necrosis factor alpha, and were expressed in a pattern similar to that induced by FG-Ad vectors encoding AdSEAP. Like AdSEAP, and runsistent with the pattern of cellular gene expression, HD-AdLacZ and HD-AdSEAP induced the recruitment of CD11b-positive leukocytes to the transduced liver within hours of administration. AdSEAP also induced a second phase of liver inflammation, consisting of inflammatory gene expression and CD3-positive lymphocytic infiltrates 7 days posttransduction. In contrast, beyond 24 h no infiltrates or expression of inflammatory genes was detected in the livers of mice receiving HD-AdSEAP. Despite the lack of liver inflammation at 7 days, Ad-specific cytotoxic T lymphocytes could be detected in mice receiving HD-AdSEAP. This lack of liver inflammation was not due to reduced transduction since levels of transgene expression and the amounts of vector DNA in the liver were equivalent in mice receiving HD-AdSEAP and AdSEAP. These results demonstrate that HD-Ad vectors induce intact innate but attenuated adaptive immune responses in vivo. [ABSTRACT FROM AUTHOR]

The key to successful cancer immunotherapy is to induce an effective anticancer immunity that will overcome the acquired cancer-specific immune tolerance. In this study, we found that dendritic cells (DCs) from multiple myeloma (MM) patients suppressed rather than induced a cancer cell-specific immune response. We demonstrated that CD4+CD25high T cells from MM patients suppressed the proliferation of activated peripheral blood lymphocytes. Further analysis illustrated that MM cell lysates or MM-specific idiotype immunoglobulins (MM Id-Ig) specifically induced the expansion of peripheral CD4+CD25highFoxP3high T regulatory (Treg) cells in vitro. Supraphysiological expression of calnexin (CNX) using lentiviral (LV) vectors in DCs of MM patients overcame the immune suppression and enhanced MM-specific CD4 and CD8 T-cell responses. However, overexpression of CNX did not affect the peripheral expansion of Treg cells stimulated by MM antigens. Thus, the immune suppression effect of Treg cells in cancer patients may be overcome by improving antigen processing in DCs, which in turn may lower the activation threshold of the immune effector cells. This concept of modulating anticancer immunity by genetically engineering cancer patients' DCs may improve immunotherapeutic regimens in cancer treatment.Molecular Therapy (2007); 16 2, 269–279. doi:10.1038/sj.mt.6300369 [ABSTRACT FROM AUTHOR]

Aim: The objective of this study was to establish the maximum tolerated dose (MTD), safety, pharmacokinetics, and anti-leukemic activity of talazoparib., Patients & Methods: This Phase I, two-cohort, dose-escalation trial evaluated talazoparib monotherapy in advanced hematologic malignancies (cohort 1: acute myeloid leukemia/myelodysplastic syndrome; cohort 2: chronic lymphocytic leukemia/mantle cell lymphoma)., Results: Thirty-three (cohort 1: n = 25; cohort 2: n = 8) patients received talazoparib (0.1-2.0 mg once daily). The MTD was exceeded at 2.0 mg/day in cohort 1 and at 0.9 mg/day in cohort 2. Grade ≥3 adverse events were primarily hematologic. Eighteen (54.5%) patients reported stable disease., Conclusion: Talazoparib is relatively well tolerated in hematologic malignancies, with a similar MTD as in solid tumors, and shows preliminary anti leukemic activity.Clinical trial registration: NCT01399840 (ClinicalTrials.gov)., Competing Interests: Financial & competing interests disclosure This study was sponsored by Biomarin/Medivation, which was acquired by Pfizer Inc. in September 2016 (grant number not applicable). AK Gopal reports research support from Merck, Janssen, Seattle Genetics, I-Mab, IgM, Pfizer, BMS, AstraZeneca, Takeda, Spectrum, and Gilead; honoraria/consulting for Janssen, Seattle Genetics, Kite, Gilead, Amgen, Merck, Pfizer, and I-Mab. R Popat reports honoraria for Janssen, Takeda, GSK, and AbbVie; consulting for Janssen, AbbVie, and GSK; travel support from Janssen and Takeda. R Popat is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Center. T Menne reports honoraria for advisory board meetings for Kite/Gilead, Amgen, Novartis, Pfizer, Celgene, Daiichi-Sankyo, and Atara; honoraria for lectures for Kite/Gilead, Takeda, Janssen, and Roche; research funding from Janssen, AstraZeneca, and Novartis. A Khwaja reports speaker fees and consulting for AbbVie, Astellas, Jazz, Novartis, and Pfizer. Y Chen is a contractor of Pfizer. MJ Cotter is an employee of Pfizer and holds Pfizer shares. GJ Mufti reports research support from BMS/Celgene and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Medical writing assistance was provided by Hannah Logan, PhD, of CMC AFFINITY, McCann Health Medical Communications, and was funded by Pfizer., (© 2021 Ajay Gopal and coauthors.)