Patients with FLT3-mutant AML Needed to Enroll on FLT3-Targeted Therapeutic Clinical Trials

We sought to identify the total number of therapeutic trials targeting FLT3-mutant acute myeloid leukemia (AML) to estimate the number of patients needed to satisfy recruitment when compared with the incidence of this mutation in the US AML population. A systematic review of all therapeutic clinical trials focusing on adult FLT3-mutated AML was conducted from 2000 to 2017. An updated search was performed using ClinicalTrials.gov for trials added between October 2017 and December 2018. Analysis was performed for ClinicalTrials.gov search results from 2000 to 2017 to provide descriptive estimates of discrepancies between anticipated clinical trial enrollment using consistently cited rates of adult participation of 1%, 3%, and 5%, as well as 10% participation identified by the American Society of Clinical Oncology in 2008. Twenty-five pharmaceutical or biological agents aimed at treating FLT3-mutant AML were identified. Pharmaceutical vs cooperative group/nonprofit support was 2.3:1, with 30 different pharmaceutical collaborators and 13 cooperative group/nonprofit collaborators. The number of patients needed to satisfy study enrollment begins to surpass the upper bound of estimated participation in 2010, noticeably surpassing projected participation rates between 2015 and 2016. The number of patients needed to satisfy study enrollment surpasses 3% and 5% rates of historical participation for US-only trials in 2017. We estimate that 15% of all US patients with FLT3-mutant AML would have to enroll in US and internationally accruing trials to satisfy requirements in 2017, or approximately 3 times the upper level of historical participation rates in the United States. The current clinical trial agenda in this space requires high percentage enrollment for sustainability

CNS Involvement in a Patient with Chronic Myeloid Leukemia

Inspite of medication compliance, some chronic myeloid leukemia (CML) patients will relapse/progress into an accelerated phase or blast crisis. Central nervous system (CNS) involvement is a rare manifestation of such a relapse. Here, we report a case of 23-year-old female who was diagnosed with CML in the accelerated phase and subsequently treated with imatinib. She developed early relapse in her CNS, and her treatment was switched to dasatinib and intrathecal chemotherapy with cytarabine and methotrexate. Her CNS disease went into remission, and she underwent matched unrelated donor (MUD) hematopoietic stem cell transplant (HSCT). We discuss various mechanisms of treatment failure, importance of vigilance for symptoms and signs of treatment failure/relapse, indications for use of different tyrosine kinase inhibitors (TKIs), and management of blast crises in CML

Representation of therapy-related myelodysplastic syndrome in clinical trials over the past 20 years

Therapy-related myelodysplastic syndrome (t-MDS), defined as MDS occurring after previous exposure to chemotherapy or radiotherapy, constitutes 10% to 20% of all MDS diagnoses. t-MDS patients tend to have higher-risk disease and worse outcomes than de novo MDS patients and are often excluded from therapeutic clinical trials. To explore this further, we extracted clinical trials across all status types registered on ClinicalTrials.gov from 1999 to 2018 studying untreated MDS patients. Using these specific search criteria, we analyzed 317 therapeutic MDS trials based on study status, therapeutic indication, eligibility criteria, and sponsor type to examine if these factors influenced t-MDS patient inclusion. Only 18 studies (5.7%) accrued 231 t-MDS patients in total, representing 3.2% of the total accrued MDS trial patient population. Fewer t-MDS patients were accrued in therapeutic trials sponsored by pharmaceutical sponsors vs nonpharmaceutical sponsors (2.8% vs 4.0%; P = .0073) . This pattern of exclusion continues in actively enrolling trials; only 5 (10%) of 49 studies specifically mention the inclusion of t-MDS patients in their eligibility criteria. Our results indicate that therapeutic MDS trials seem to exclude t-MDS patients, rendering study results less applicable to this subset of MDS patients, who often have poor outcomes. Our study emphasizes the importance of the recent focus by National Cancer Institute cooperative groups and societies to broaden eligibility criteria for all patients

Real‐world genomic testing and treatment patterns of newly diagnosed adult acute myeloid leukemia patients within a comprehensive health system

Abstract Background We evaluated the frequency of genomic testing and treatment patterns by age category in patients with newly diagnosed (ND) acute myeloid leukemia (AML) treated in both academic‐ and community‐based health systems within a single Midwestern State. Methods Retrospective analysis of data from the Indiana University Health System Enterprise Data Warehouse and two local cancer registries, of 629 patients aged ≥18 years with ND AML during 2011–2018. Primary outcome variables were, proportion of patients with genomic analysis and frequency of mutations. Chemotherapy was categorized as “standard induction” or “other chemotherapy”/targeted therapy, and hypomethylating agents. Results Overall, 13% of ND AML patients between 2011 and 2018 had evidence of a genomic sequencing report with a demonstrated increase to 37% since 2016. Genomic testing was more likely performed in patients: aged ≤60 years than >60 years (45% vs. 30%; p = 0.03), treated in academic versus community hospitals (44% vs. 26%; p = 0.01), and in chemotherapy recipients than non‐therapy recipients (46% vs. 19%; p < 0.001). Most common mutations were ASXL1, NPM1, and FLT3. Patients ≥75 years had highest proportion (46%) of multiple (≥3) mutations. Overall, 31.2% of patients with AML did not receive any therapy for their disease. This subgroup was older than chemotherapy recipients (mean age: 71.4 vs. 55.7 years, p < 0.001), and was highest (66.2%) in patients ≥75 years. Conclusions Our results highlight the unmet medical need to increase access to genomic testing to afford treatment options, particularly to older AML patients in the real‐world setting, in this new era of targeted therapies