Global Trial Representation and Availability of Tyrosine Kinase Inhibitors for Treatment of Chronic Myeloid Leukemia.

: Evaluating clinical trial representation for countries with different socio-demographic index (SDI) and tyrosine kinase inhibitor (TKI) availability for chronic myeloid leukemia (CML). : CML incidence rates (IRs) and disability-adjusted life years (DALYs) (1999-2019) from the Institute of Health Metrics and Evaluation were analyzed. Trials investigating TKI use in CML were obtained from ClinicalTrials.

Treatment patterns and outcomes of high-grade immune checkpoint inhibitor-related pneumonitis in an oncology hospitalist service.

Purpose: Immune checkpoint inhibitors (ICI) have become standard of care for some types of lung cancer. Along with expanding usage comes the emergence of immune-related adverse events (irAEs), including ICI-related pneumonitis (ICI-P). Treatment guidelines for managing irAEs have been developed; however, how clinicians manage irAEs in the real-world setting is less well known.

Representation of the population in need for pivotal clinical trials in lymphomas.

Despite the advances in cancer outcomes, significant health disparities persist. Several new agents have been recently approved for treatment of lymphomas, leading to improved outcomes. Extending the benefits of these new agents starts by adequate enrollment of all affected patient populations.

A Phase I Study of the Non-Receptor Kinase Inhibitor Bosutinib in Combination with Pemetrexed in Patients with Selected Metastatic Solid Tumors.

Src is overexpressed in various cancers, including 27% of non-small cell lung cancer NSCLC, and is correlated with poor clinical outcomes. We hypothesize that Src kinase inhibitors, including Bosutinib, may exhibit clinical synergy in combination with the antifolate drug pemetrexed. In this Phase I, dose-escalation, safety, and maximum tolerated dose (MTD)-determining study, 14 patients with advanced metastatic solid tumors that had progressed on "standard of care" chemotherapy were enrolled in a 3 + 3 dose escalation study.

Are Pivotal Clinical Trials for Drugs Approved for Leukemias and Multiple Myeloma Representative of the Population at Risk?

Purpose: There are significant disparities in care and outcomes for patients with leukemias and multiple myeloma (MM). To evaluate the extent to which clinical trials (CTs) match the demographic and geographic diversity of populations affected by leukemias and MM.

Methods: CTs leading to drug approval were identified from the US Food and Drug Administration databases.

Activity of decitabine as maintenance therapy in core binding factor acute myeloid leukemia.

Background: Posttherapy measurable residual disease (MRD) positivity in core binding factor acute myeloid leukemia (CBF-AML) is associated with shorter relapse-free survival (RFS). Elimination of MRD measured via quantitative reverse transcription polymerase chain reaction (qRTPCR) for disease specific transcripts can potentially lead to better outcomes in CBF-AML.

Methods: We prospectively monitored the MRD using qRTPCR and flow cytometry on bone marrow samples in patients with newly diagnosed CBF-AML who received decitabine (DAC) maintenance therapy after fludarabine/cytarabine/G-CSF (FLAG)-based induction/consolidation regimen.

Sudden Blast Crisis After Excellent Initial Response in Chronic Myeloid Leukemia.

Sudden blast crisis is an uncommon phenomenon in chronic myeloid leukemia (CML) patients who are being treated with tyrosine kinase inhibitors (TKIs). Despite well-defined guidelines to treat and monitor the disease, it is difficult to predict the occurrence of a sudden blast crisis. Research directed towards improving guidelines in choosing the appropriate TKIs and better monitoring protocols could help prevent such unfortunate outcomes.

Outcomes in patients with newly diagnosed TP53-mutated acute myeloid leukemia with or without venetoclax-based therapy.

Background: Venetoclax (VEN) in combination with a hypomethylating agent (HMA) has become the standard of care for patients aged >75 years and for those not eligible for intensive chemotherapy who have newly diagnosed acute myeloid leukemia (AML). The benefit of VEN-based therapy in patients who have newly diagnosed AML with mutations in the TP53 gene (TP53 ) over standard therapy is undefined.

Methods: In this single-institutional, retrospective analysis, the authors assessed the clinical outcomes of 238 patients with newly diagnosed TP53 AML and compared the clinical characteristics, response to different therapies, and outcomes of those who received VEN-based (n = 58) and non-VEN-based (n = 180) regimens.

Review of New-Generation Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia.

Purpose Of Review: In this review, we analyzed the available data from clinical trials with new tyrosine kinase inhibitors (TKIs) under development and how to consider chronic myeloid leukemia (CML) patients who had either resistance or intolerance to current TKIs for treatment with such agents.

Recent Findings: Nearly 50% of CML patients treated with TKIs frontline have required a change of therapy by 10 years. Second-line therapy is effective (by achievement of complete cytogenetic response) in only approximately 50% of patients, and available third-generation TKI has been marred by concerns of arterio-occlusive events.

Inflammatory Myositis in Cancer Patients Receiving Immune Checkpoint Inhibitors.

Objective: To estimate the incidence of immune checkpoint inhibitor-related myositis (ICI-myositis) in cancer patients receiving ICIs, and to report associated clinical manifestations, patterns of care, and outcomes.

Methods: We identified a retrospective cohort of patients receiving ICIs between 2016 and 2019 seen at the University of Texas MD Anderson Cancer Center. Cases of ICI-myositis were identified using International Classification of Disease codes and confirmed by reviewing medical records and pathology, as available.

Clinical characteristics and outcomes in patients with acute myeloid leukemia with concurrent FLT3-ITD and IDH mutations.

Background: Isocitrate dehydrogenase (IDH1 and IDH2) mutations commonly co-occur with FMS-like tyrosine kinase 3 (FLT3) mutations in patients with acute myeloid leukemia (AML).

Methods: The authors reviewed cases of patients with FLT3-internal tandem duplication (FLT3-ITD)-mutated AML with concurrent IDH mutations diagnosed between January 2011 and December 2018.

Results: A total of 91 patients with FLT3-ITD and IDH1 or IDH2 "double-mutated" AML were identified; 36 patients had concurrent FLT3-ITD/IDH1 mutations (18 in the frontline and 18 in the recurrent and/or refractory [R/R] setting) and 55 patients had concurrent FLT3-ITD/IDH2 mutations (37 in the frontline and 18 in the R/R setting).

The effect of eltrombopag in managing thrombocytopenia associated with tyrosine kinase therapy in patients with chronic myeloid leukemia and myelofibrosis.

Approximately 20-50% patients with chronic phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs) or with myelofibrosis (MF) treated with ruxolitinib develop grade ≥3 thrombocytopenia needing treatment interruptions and dose reductions. We conducted a non-randomized, phase II, single-arm study to determine the efficacy of eltrombopag for patients with CML or MF with persistent thrombocytopenia while on TKI or ruxolitinib. Eltrombopag was initiated at 50 mg/day, with dose escalation up to 300 mg daily allowed every 2 weeks.

The clinical impact of time to response in de novo accelerated-phase chronic myeloid leukemia.

We aimed to describe the impact of time to response on the outcomes of 75 patients with accelerated-phase chronic myeloid leukemia (CML-AP) at diagnosis. Patients had at least 1 feature of AP: blasts ≥15% (n = 2), basophils ≥20% (n = 19), platelets <100 × 10 /L (n = 7), cytogenetic clonal evolution (n = 34), or more than one factor (n = 13). Thirty-three patients received imatinib; 42 received a second-generation tyrosine kinase inhibitor (2GTKI) (19 dasatinib and 23 nilotinib).

Major Stressful Life Events and Risk of Developing Lung Cancer: A Case-Control Study.

Background: Lung cancer is the leading cause of cancer-related mortality and is strongly linked with smoking. We sought to determine whether major stressful life events (e.g.

Azacitidine in fludarabine-refractory chronic lymphocytic leukemia: a phase II study.

Background: Treatment of fludarabine-refractory disease in patients with chronic lymphocytic leukemia (CLL) remains a challenge. Because a recent genome-wide methylation analysis of CLL cells suggested that demethylation therapy might be beneficial in CLL, we conducted a phase II trial with the hypomethylating agent azacitidine in patients with recurrent fludarabine-refractory CLL.

Patients And Methods: Nine patients with recurrent fludarabine-refractory Rai stage IV CLL (median age, 74 years; range, 49-81 years) were enrolled.