Remembering the forgotten child: the role of immune checkpoint inhibition in patients with human immunod eficiency virus and cancer.

Patients with human immunodeficiency virus (HIV) infection have a high risk of developing virally-mediated cancers. These tumors have several features that could make them vulnerable to immune checkpoint inhibitors (ICIs) including, but not limited to, increased expression of the CTLA-4 and PD-1 checkpoints on their CD4+ T cells. Even so, HIV-positive patients are generally excluded from immunotherapy cancer clinical trials due to safety concerns. Hence, only case series have been published regarding HIV-positive patients with cancer who received ICIs, but these reports of individuals with a variety of malignancies demonstrate that ICIs have significant activity, exceeding a 65% objective response rate in Kaposi sarcoma. Furthermore, high-grade immune toxicities occurred in fewer than 10% of treated patients. The existing data suggest that the underlying biologic mechanisms that mediate development of cancer in HIV-infected patients should render them susceptible to ICI treatment. Preliminary, albeit limited, clinical experience indicates that checkpoint blockade is both safe and efficacious in this setting. Additional clinical trials that include HIV-positive patients with cancer are urgently needed

Remembering the forgotten child: the role of immune checkpoint inhibition in patients with human immunod eficiency virus and cancer.

Patients with human immunodeficiency virus (HIV) infection have a high risk of developing virally-mediated cancers. These tumors have several features that could make them vulnerable to immune checkpoint inhibitors (ICIs) including, but not limited to, increased expression of the CTLA-4 and PD-1 checkpoints on their CD4+ T cells. Even so, HIV-positive patients are generally excluded from immunotherapy cancer clinical trials due to safety concerns. Hence, only case series have been published regarding HIV-positive patients with cancer who received ICIs, but these reports of individuals with a variety of malignancies demonstrate that ICIs have significant activity, exceeding a 65% objective response rate in Kaposi sarcoma. Furthermore, high-grade immune toxicities occurred in fewer than 10% of treated patients. The existing data suggest that the underlying biologic mechanisms that mediate development of cancer in HIV-infected patients should render them susceptible to ICI treatment. Preliminary, albeit limited, clinical experience indicates that checkpoint blockade is both safe and efficacious in this setting. Additional clinical trials that include HIV-positive patients with cancer are urgently needed

Bone Metastasis as the Only Metastatic Site in a Patient with Pancreatic Cancer following Distal Pancreatectomy

Pancreatic cancer remains a challenge both diagnostically and therapeutically. The typical sites of metastases in pancreatic cancer include the liver and peritoneum. Other less common sites are the lung, brain, kidney, and bone. Skeletal metastases are less prevalent in occurrence but contribute to significant morbidity associated with pancreatic cancer. The prevalence of osseous metastases remains unknown but has been estimated to be between 5% and 20%. The most common osseous lesions are osteolytic in nature, but the osteoblastic ones are extremely rare. Here, we report an interesting case of pancreatic adenocarcinoma with exclusive bone metastases and discuss briefly the possible pathogenesis

Comprehensive Genomic Profiling Reveals Diverse but Actionable Molecular Portfolios across Hematologic Malignancies: Implications for Next Generation Clinical Trials

Background: The translation of genomic discoveries to the clinic is the cornerstone of precision medicine. However, incorporating next generation sequencing (NGS) of hematologic malignancies into clinical management remains limited. Methods: We describe 235 patients who underwent integrated NGS profiling (406 genes) and analyze the alterations and their potential actionability. Results: Overall, 227 patients (96.5%) had adequate tissue. Most common diagnoses included myelodysplastic syndrome (22.9%), chronic lymphocytic leukemia (17.2%), non-Hodgkin lymphoma (13.2%), acute myeloid leukemia (11%), myeloproliferative neoplasm (9.2%), acute lymphoblastic leukemia (8.8%), and multiple myeloma (7.5%). Most patients (N = 197/227 (87%)) harbored ≥1 genomic alteration(s); 170/227 (75%), ≥1 potentially actionable alteration(s) targetable by an FDA-approved (mostly off-label) or an investigational agent. Altogether, 546 distinct alterations were seen, most commonly involving TP53 (10.8%), TET2 (4.6%), and DNMT3A (4.2%). The median tumor mutational burden (TMB) was low (1.7 alterations/megabase); 12% of patients had intermediate or high TMB (higher TMB correlates with favorable response to anti-PD1/PDL1 inhibition in solid tumors). In conclusion, 96.5% of patients with hematologic malignancies have adequate tissue for comprehensive genomic profiling. Most patients had unique molecular signatures, and 75% had alterations that may be pharmacologically tractable with gene- or immune-targeted agents

Comprehensive Genomic Profiling Reveals Diverse but Actionable Molecular Portfolios across Hematologic Malignancies: Implications for Next Generation Clinical Trials.

Background: The translation of genomic discoveries to the clinic is the cornerstone of precision medicine. However, incorporating next generation sequencing (NGS) of hematologic malignancies into clinical management remains limited. Methods: We describe 235 patients who underwent integrated NGS profiling (406 genes) and analyze the alterations and their potential actionability. Results: Overall, 227 patients (96.5%) had adequate tissue. Most common diagnoses included myelodysplastic syndrome (22.9%), chronic lymphocytic leukemia (17.2%), non-Hodgkin lymphoma (13.2%), acute myeloid leukemia (11%), myeloproliferative neoplasm (9.2%), acute lymphoblastic leukemia (8.8%), and multiple myeloma (7.5%). Most patients (N = 197/227 (87%)) harbored ≥1 genomic alteration(s); 170/227 (75%), ≥1 potentially actionable alteration(s) targetable by an FDA-approved (mostly off-label) or an investigational agent. Altogether, 546 distinct alterations were seen, most commonly involving TP53 (10.8%), TET2 (4.6%), and DNMT3A (4.2%). The median tumor mutational burden (TMB) was low (1.7 alterations/megabase); 12% of patients had intermediate or high TMB (higher TMB correlates with favorable response to anti-PD1/PDL1 inhibition in solid tumors). In conclusion, 96.5% of patients with hematologic malignancies have adequate tissue for comprehensive genomic profiling. Most patients had unique molecular signatures, and 75% had alterations that may be pharmacologically tractable with gene- or immune-targeted agents