Role of Checkpoint Inhibitors in the Management of Gastroesophageal Cancers.

PURPOSE: This article reviews the essential clinical trials that have led to these immunotherapy approvals and explores the use of predictive biomarkers, such as PD-L1 expression and MSI status, to identify patients who are most likely to benefit from immunotherapies. METHODS: This case review series describe findings from different clinical trials and contribute to the evolving understanding of the role of CPIs in managing advanced gastroesophageal cancers and may lead to improved treatment options and patient outcomes. Ongoing clinical trials also hold promise for expanding treatment options and improving patient outcomes in the future. METHODS: The systematic review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol has not been registered. A systematic literature review was conducted to identify relevant clinical trials and studies that describe the role of immune checkpoint inhibitors in managing advanced gastroesophageal cancers. Electronic database (PubMed, Clinicaltrials.gov, Society of Immunotherapy of Cancer, Aliment Pharmacology & Therapeutics, BMC cancer, Molecular Cancer Research, Nature Reviews Molecular Cell Biology, American Association for Cancer Research, Science, Nature, Cancer Discovery, Journal of the National Cancer Institute, Advanced Immunology, Oncotarget, Nature Medicine, Nature Genetics, Gut, Pathology and Oncology Research, Journal of Clinical Oncology, The New England Journal of Medicine, Gastrointestinal oncology, JAMA Oncology, Journal of Gastrointestinal Oncology, Current Oncology, Annals of Oncology, The Lancet, JCO Oncology Practice, Future Oncology, Gastric Cancer, CA: A Cancer Journal for Clinicians, American Journal of Gastroenterology, Gastroenterology, Journal of the National Cancer Institute, International Journal of Epidemiology, Helicobacter, Gastroenterology Review) were searched using a combination of relevant keywords and MESH terms. The search encompassed articles published up to 5/2023. Additionally, manual searches of reference lists of selected articles and pertinent review papers were conducted to ensure comprehensive coverage of relevant studies. Studies were included if they provided insights into clinical trials evaluating the efficacy and safety of CPIs in treating advanced gastroesophageal cancers. Relevant case reviews and trials exploring combination therapies involving CPIs were also considered. Articles discussed in the utilization of predictive biomarkers were included to assess their impact on treatment outcomes. Data from selected studies were extracted to inform the narrative review. Key findings were summarized, including clinical trial designs, patient populations, treatment regimens, response rates, progression-free survival (PFS), overall survival (OS), and adverse events. The role of predictive biomarkers, particularly PD-L1 expression and MSI status, in identifying patients likely to benefit from CPIs was critically evaluated based on study results. Ongoing clinical trials investigating novel combination strategies and exploring the broader scope of CPIs in gastroesophageal cancers were also highlighted. The collected data were synthesized to provide a comprehensive overview of the crucial clinical trials that have contributed to the approval of CPIs for advanced gastroesophageal cancers. The role of CPIs in different lines of therapy, including first-line regimens, was discussed. Furthermore, the evolving landscape of predictive biomarkers was examined, emphasizing their potential significance in optimizing patient selection for CPI therapy. Ongoing clinical trials were reviewed to underscore the continuous efforts in expanding treatment options and improving patient outcomes in the future.

Cancer patients and COVID-19: Mortality, serious complications, biomarkers, and ways forward.

The SARS-CoV-2 (COVID-19) pandemic has particularly serious consequences for cancer patients, as they are at high risk for severe complications and mortality due to the virus since cancer patients are immunocompromised. Preliminary evidence suggests that patients with hematological, and metastatic malignancies are particularly susceptible to developing severe COVID-19 illness, which leads to poor prognosis. Biomarkers including C-reactive protein and interleukin-6 may be predictors of outcome and, therefore, crucial in assessing COVID-19 illness severity in cancer patients. A patient-specific risk and benefit inventory should be completed, and expert guidelines consulted when deciding to continue or postpone therapeutic interventions. This review presents preliminary evidence of COVID-19 infection and its impact on cancer, as well as discussion of general guidelines for the treatment and management of cancer patients with COVID-19.

A phase II study of pomalidomide, daily oral cyclophosphamide, and dexamethasone in relapsed/refractory multiple myeloma.

Relapsed/refractory multiple myeloma patients treated with pomalidomide and dexamethasone have an overall response rate (ORR) of ∼30% and median progression-free survival (PFS) of 4-5 months. Previous studies explored addition of weekly cyclophosphamide, but we hypothesized that daily dosing allows for better synergy. We report the open-label, single-center phase II study of pomalidomide, daily cyclophosphamide and weekly dexamethasone (PCD). Thirty-three patients were evaluable for efficacy and underwent 28-day cycles of pomalidomide (4 mg/day, D1-21), cyclophosphamide (50 mg b.i.d., D1-21) and weekly dexamethasone. All were lenalidomide-refractory and 55% were refractory to lenalidomide and proteasome inhibitor. ORR was 73%; median PFS and overall survival were 13.3 months and 57.2 months respectively. Grade 3/4 toxicities were primarily hematologic but manageable with dose reductions. Early disease progression correlated with MYC expression and flow cytometry demonstrates an activated microenvironment post-PCD. Addition of metronomic cyclophosphamide to pomalidomide and dexamethasone is a cost-effective, oral regimen with encouraging PFS.

Barriers to Allogeneic Hematopoietic Stem Cell Transplantation for Human T Cell Lymphotropic Virus 1-Associated Adult T Cell Lymphoma-Leukemia in the United States: Experience from a Large Cohort in a Major Tertiary Center.

In the United States adult T cell lymphoma-leukemia (ATLL) carries a dismal prognosis and mainly affects immigrants from human T cell lymphotropic virus 1 endemic areas. Allogeneic hematopoietic stem cell transplant (alloHSCT) can be effective and is recommended as an upfront treatment in the National Comprehensive Cancer Network guidelines. We studied the barriers to alloHSCT in one of the largest ATLL populations in the United States. Comprehensive chart and donor registry reviews were conducted for 88 ATLL patients treated at Montefiore Medical Center from 2003 to 2018. Among 49 patients with acute and 32 with lymphomatous subtypes, 48 (59.5%) were ineligible for alloHSCT because of early mortality (52%), loss to follow-up (21%), uninsured status (15%), patient declination (10%), and frailty (2%). Among 28 HLA-typed eligible patients (34.6%), matched related donors were identified for 7 (25%). A matched unrelated donor (MUD) search yielded HLA-matched in 2 patients (9.5%), HLA mismatched in 6 (28.5%), and no options in 13 (62%). Haploidentical donors were identified for 6 patients (46%) with no unrelated options. There were no suitable donors for 7 (25%) alloHSCT-eligible patients. The main limitation for alloHSCT after donor identification was death from progressive disease (82%). AlloHSCT was performed in 10 patients (12.3%) and was associated with better relapse-free survival (26 versus 11 months, P = .04) and overall survival (47 versus 10 months, P = .03). Early mortality and progressive disease are the main barriers to alloHSCT, but poor follow-up, uninsured status, and lack of suitable donor, including haploidentical, are also substantial limitations that might disproportionally affect this vulnerable population. AlloHSCT can achieve long-term remissions, and strategies aiming to overcome these barriers are urgently needed to improve outcomes in ATLL.