Disparity in Utilization of Multiagent Therapy for Acute Promyelocytic Leukemia in the United States

BackgroundDespite high rate of cure in acute promyelocytic leukemia (APL) in clinical trials, outcomes in real-world practice are dismal. We utilized National Cancer Database (NCDB) to explore utilization of multiagent therapy in APL and identify any disparities in treatment in real-world practices.Patients and MethodsNCDB categorizes use of systemic chemotherapy into single agent versus multiagent therapy. Some patients received hormonal therapy, immunotherapy, and unknown therapy; details of these treatments could not be ascertained. We therefore used multiple logistic regression analysis to evaluate effects of covariates on the probability of multiagent therapy use in 6678 patients.ResultsCompared to patients >60 years, patients aged 0 to 18 years (hazard ratio[HR] 3.2, 95% confidence interval [CI] 1.8-5.5, P< .0001), 19 to 40 years (HR 1.6, 95% CI 1.03-2.54, P= .03), and 41 to 60 years (HR 1.6, 95% CI 1.3-1.9, P< .0001) were more likely to receive multiagent therapy. Patients with Charlson comorbidity index (CCI) of 0 (HR 1.6, 95% CI 1.2-2.3, P= .001) and CCI of 1 (HR 1.4, 95% CI 1.0-1.9, P= .04) had a higher likelihood of receiving multiagent therapy than patients with CCI ≥ 3. Patients treated at academic cancer centers, compared to those treated at community cancer center (HR 0.5, 95% CI 0.3-0.7, P= .001), comprehensive community cancer center (HR 0.7, 95% CI 0.6-0.8, P< .0001), and integrated network cancer center (HR 0.8, 95% CI 0.6-0.9, P= .02) were more likely to be treated with multiagent therapy. Compared to the patients with private insurance, those with Medicaid had increased likelihood (HR 1.2, 95% CI 1.0-1.4, P= .04) whereas uninsured patients had a lower likelihood of receiving multiagent therapy (HR 0.6, 95% CI 0.5-0.8, P= .0005).ConclusionTo our knowledge, this study is the first and the largest scale analysis of treatment practices in APL in real-world practices. Our findings highlight significant disparities in treatment of APL based on age, insurance, and health-system factors.     

Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

Building new standards to prevent harm from medication errors in children with cancer

• Children with cancer receive many medications outside the hospital administered by their caregivers.
• The study by Walsh et al. shows the number and types of medication errors in these patients. The study includes data from three different centers.
• Importantly, the study shows the types of errors that cause harm. The authors describe how the harmful errors can be prevented.
• We suggest ways these results can be used to identify which patients and families will benefit from additional attention. Providing more help at clinic and in the home may help prevent harmful medication errors in children with cancer.

     

Inhibition of BTK and PI3Kδ impairs the development of human JMML stem and progenitor cells

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Dual-target inhibitors of bromodomain-containing protein 4 (BRD4) in cancer therapy: Current situation and future directions

Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.     

Association between C1236T Genetic Variant of ABCB1 Gene and Molecular Response to Imatinib in Indonesian Chronic Myeloid Patients

Objective: Imatinib is the first-line drug used for the treatment of chronic myeloid leukemia (CML) patients due to high molecular response and overall survival rate. However, some patients develop resistance to imatinib even after attaining a response. Mutation in ABCB1 efflux transporters is one of the known mechanisms of resistance to imatinib in chronic myeloid leukemia patients. This study was aimed to investigate the association of ABCB1 C1236T polymorphism in Indonesian chronic myeloid patients with molecular response to imatinib treatment. Methods: We analyzed 120 samples from chronic myeloid leukemia patients in the chronic phase, who had been on imatinib treatment for at least 12 months. We analyzed the C1236T variant of the ABCB1 gene using PCR, followed by direct sequencing, and associate them with the achievement of major molecular response (MMR). Results: The major molecular response was achieved in 28% of patients. The frequencies of the SNPs were CC (40%), CT (46%), and TT (14%). Our result showed that there was a lack of association between polymorphism of ABCB1 C1236T and imatinib response in Indonesian patients, with OR = 0.646 (95% CI: 0.283, 1.471; p>0.05). Conclusion: There was no association between ABCB1 C1236T variants with the major molecular response in Indonesian chronic myeloid leukemia patients receiving imatinib treatment.