Molecular response in newly diagnosed chronic-phase chronic myeloid leukemia: prediction modeling and pathway analysis.

Tyrosine kinase inhibitor therapy revolutionized chronic myeloid leukemia treatment and showed how targeted therapy and molecular monitoring could be used to substantially improve survival outcomes. We used chronic myeloid leukemia as a model to understand a critical question: why do some patients have an excellent response to therapy, while others have a poor response? We studied gene expression in whole blood samples from 112 patients from a large phase III randomized trial (clinicaltrials gov. Identifier: NCT00471497), dichotomizing cases into good responders (BCR::ABL1 ≤10% on the International Scale by 3 and 6 months and ≤0.1% by 12 months) and poor responders (failure to meet these criteria). Predictive models based on gene expression demonstrated the best performance (area under the curve =0.76, standard deviation =0.07). All of the top 20 pathways overexpressed in good responders involved immune regulation, a finding validated in an independent data set. This study emphasizes the importance of pretreatment adaptive immune response in treatment efficacy and suggests biological pathways that can be targeted to improve response.

Patient and Caregiver Insights into the Disease Burden of Myelodysplastic Syndrome.

A diagnosis of myelodysplastic syndrome (MDS) is typically unexpected and can be difficult for patients to grasp. Not only is MDS a complicated disease to understand, which can contribute to stress and anxiety, but it also has an uncertain prognosis, which can be emotionally paralyzing. Not surprisingly, emotional distress and the symptom burden of MDS, including extreme fatigue due to cytopenias, negatively impact a patient's quality of life (QOL). Studies have shown that patient-centered care-including greater physician understanding of the disease burden their patients experience, discussing and establishing agreed-on treatment goals, and including patients in the decision-making process about their care-may help improve patient QOL. To better understand patient and caregiver experiences with MDS and how the disease impacts QOL, a small survey was conducted of patients with MDS or leukemia and their caregivers on an online health network. Among the 30 respondents who completed the survey, four had MDS and one was a caregiver for a patient with MDS. Here we focus on the five MDS respondents and contextualize the findings with personal experiences from a patient and physician perspective. The patient perspective was provided by John Soper, PhD, DABCC, who was diagnosed with MDS in 2019. Dr Soper is a retired board-certified clinical chemist and a member of the MDS Foundation. The physician perspective was provided by Dr Ruben Mesa, Executive Director of the Mays Cancer Center at UT Health San Antonio MD Anderson. The survey responses and the accompanying patient and physician perspectives highlight the importance of open communication between patients and their healthcare provider to better serve those with MDS and improve their QOL.

Efficacy and safety of a novel dosing strategy for ruxolitinib in the treatment of patients with myelofibrosis and anemia: the REALISE phase 2 study.

Anemia is a frequent manifestation of myelofibrosis (MF) and there is an unmet need for effective treatments in anemic MF patients. The REALISE phase 2 study (NCT02966353) evaluated the efficacy and safety of a novel ruxolitinib dosing strategy with a reduced starting dose with delayed up-titration in anemic MF patients. Fifty-one patients with primary MF (66.7%), post-essential thrombocythemia MF (21.6%), or post-polycythemia vera MF (11.8%) with palpable splenomegaly and hemoglobin <10 g/dl were included. Median age was 67 (45-88) years, 41.2% were female, and 18% were transfusion-dependent. Patients received 10 mg ruxolitinib b.i.d. for the first 12 weeks, then up-titrations of up to 25 mg b.i.d. were permitted, based on efficacy and platelet counts. Overall, 70% of patients achieved a ≥50% reduction in palpable spleen length at any time during the study. The most frequent adverse events leading to dose interruption/adjustment were thrombocytopenia (17.6%) and anemia (11.8%). Patients who had a dose increase had greater spleen size and higher white blood cell counts at baseline. Median hemoglobin levels remained stable and transfusion requirements did not increase compared with baseline. These results reinforce the notion that it is unnecessary to delay or withhold ruxolitinib because of co-existent or treatment-emergent anemia.

Tyrosine kinase inhibitor therapy discontinuation in patients with chronic myeloid leukemia in chronic phase in the United States after clinical practice guideline updates.

A physician survey (July 2019-August 2019) and a retrospective patient medical chart review (November 2019-December 2019) were conducted to assess TKI therapy discontinuation practice in patients with Ph + CML-CP in the US after the publication of practice guidelines updated with recommendations for TKI discontinuation. After guideline updates, 90% of physicians from the survey reported attempting TKI discontinuation and 24% of their patients discontinued TKI after achieving an adequate response. Although TKI therapy discontinuation practice is increasing, particularly in community-based practice, a little more than half of physicians were aware of these updated guidelines resulting in TKI discontinuation attempted under suboptimal conditions, mainly limited to first-line TKI therapy, with more than half of physicians without access to at least MR4.5 sensitivity level of detection monitoring. Stricter response criteria per guideline recommendations were observed to relate to lower relapse rates following TKI discontinuation, emphasizing the importance of communicating these recommendations and access to adequate monitoring tools.

Treatment patterns and outcomes in patients with myelodysplastic syndromes treated with hypomethylating agents: a SEER-Medicare analysis.

To describe real-world treatment patterns and outcomes among adult patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMA), patients were identified in the SEER-Medicare database (01/2006-12/2016); 3,046 patients with MDS treated with HMA were included. An algorithm was developed to categorize patients into MDS risk groups: the majority of patients were classified as Higher-risk (70.9%), 8.0% as Intermediate-risk, and 21.1% as Unknown-risk. Overall, 77.4% of patients initiated azacitidine and 22.6% decitabine; they received an average of 5.1 index-HMA cycles, of which 90.9% were complete with a median cycle duration of 28 days. Median survival was 11.6, 18.4, and 19.1 months for the Higher-risk, Intermediate-risk, and Unknown-risk groups, respectively. Median time-to-AML transformation was 19.3 months for the Higher-risk group and 50.4 months for the Intermediate-risk group (not reached for Unknown-risk). Data highlight the unmet medical needs of patients with MDS treated with HMA, particularly for the Higher-risk MDS group.

Healthcare resource utilization and costs in patients with myelodysplastic syndromes treated with hypomethylating agents: a SEER-Medicare analysis.

AIMS: To describe healthcare resource utilization (HRU) and costs in patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMA) based on HMA-treatment response. MATERIALS AND METHODS: SEER-Medicare data (January 2006-December 2016) were used to identify adults diagnosed with MDS (SEER: January 2009-December 2015) initiated on HMA (index date). HMA-treatment success (indicators: ≥7 HMA cycles, stem cell transplantation, and transfusion independence) or failure (indicators: acute myeloid leukemia [AML], AML-like treatment, and death) was determined using a claim-based algorithm. HRU and costs were assessed from the index date to 1-year post-index, overall and stratified by HMA-treatment success or failure. Among patients with HMA-treatment failure, HRU and costs were also assessed from failure to 1-year post-failure. RESULTS: The study included 3,046 patients (mean age: 77.4 years; females: 36.8%). Rates of HMA-treatment success and failure were 44.4% and 76.2%, respectively (20.6% had HMA-treatment success then failure). Overall, patients had 15.2 inpatient admissions per-100-patients-per-month (median follow-up: 5.9 months). Patients with HMA-treatment success had 7.5 inpatient admissions per-100-patients-per-month (median follow-up: 12.0 months), while those with HMA-treatment failure had 20.4 and 35.3 admissions per-100-patients-per-month pre- and post-HMA-treatment failure, respectively (median follow-up: 4.3 and 1.8 months, pre- and post-HMA-treatment failure, respectively). Mean total healthcare costs were $12,494 per-patient-per-month overall, $8,069 per-patient-per-month among patients with HMA-treatment success, and $13,809 and $19,242 per-patient-per-month pre- and post-HMA-treatment failure, respectively. Outpatient costs (68.3%) were the main contributor of total healthcare costs overall, while inpatient costs (80.3%) were the main cost driver post-HMA-treatment failure. LIMITATIONS: Without available laboratory test results, clinical indicators observed in claims were used to assess HMA-treatment response. CONCLUSIONS: Over 75% of patients with MDS failed HMA-treatment within 6 months of initiation and were observed with more inpatient admissions than those with HMA-treatment success, translating into substantially higher healthcare costs. HMA-treatment failure results in an important economic burden in MDS patients.

MERGE: A Multinational, Multicenter Observational Registry for Myeloproliferative Neoplasms in Asia, including Middle East, Turkey, and Algeria.

Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal disorders of the bone marrow, and are associated with a high disease burden, reduced quality of life (QOL), and shortened survival. This multinational, multicenter, non-interventional registry "MERGE" was initiated with an objective to collect data on the epidemiological indices of classical Ph-MPNs, existing treatment patterns, and impact of MPNs on health-related QOL in various countries/regions in Asia, including the Middle East, Turkey, and Algeria. Of the 884 eligible patients with MPNs, 169 had myelofibrosis (MF), 301 had polycythemia vera (PV), 373 had essential thrombocythemia (ET), and 41 had unclassified MPNs. The median age was 58 years (range, 47-66 years), and 50% of patients were males. The prevalence and incidence of MPNs were estimated to be 57-81 and 12-15 per 100 000 hospital patients per year over the last 4 years, respectively, in these countries. Total symptom score (mean [standard deviation; SD]) at baseline was highest in patients with MF (23.5 [17.47]) compared with patients with ET (14.6 [14.26]) and PV (16.6 [14.84]). Patients with ET had a lower mean (SD) number of inpatient visits (0.9 [0.77] days), and patients with MF had more outpatient visits (5.2 [3.17] days) on an average, compared with the entire MPN group. The study showed that patients with MPNs have a severe disease burden and reduced QOL. A discordance between physician and patient perception of symptom assessment was observed in this study (International clinical trials registry ID: CTRI/2014/05/004598).