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PANTHER was a global, randomized phase 3 trial of pevonedistat plus azacitidine (n = 227) vs azacitidine monotherapy (n = 227) in patients with newly diagnosed higher-risk myelodysplastic syndromes (MDS) (n = 324), higher-risk chronic myelomonocytic leukemia (n = 27), or acute myeloid leukemia (AML) with 20-30% blasts (n = 103). The primary endpoint was event-free survival (EFS). In the intent-to-treat (ITT) population median EFS was 17.7 months with pevonedistat plus azacitidine vs 15.7 months with azacitidine (hazard ratio [HR], 0.968 [95% confidence interval (CI), 0.757-1.238], P = 0.557) and in the higher-risk MDS cohort median EFS was 19.2 vs 15.6 months (HR, 0.887 [95% CI, 0.659-1.193, P = 0.431). Median overall survival (OS) in the higher-risk MDS cohort was 21.6 vs 17.5 months (HR, 0.785, P = 0.092]), and in patients with AML with 20-30% blasts was 14.5 vs 14.7 months (HR, 1.107, P = 0.664). In a post-hoc analysis, median OS in the higher-risk MDS cohort for patients receiving >3 cycles was 23.8 vs 20.6 months (P = 0.021) and for >6 cycles was 27.1 vs 22.5 months (P = 0.008). No new safety signals were identified, and azacitidine dose intensity was maintained. Common hematologic grade ≥3 treatment emergent adverse events were anemia (33% vs 34%), neutropenia (31% vs 33%), and thrombocytopenia (30% vs 30%). These results underscore the importance of large, randomized controlled trials in these heterogeneous myeloid diseases and the value of remaining on therapy >3 cycles. (ClinicalTrials.gov, NCT03268954).

SummaryThe Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose‐optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re‐escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2–75·1%) achieved major molecular response (BCR‐ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re‐escalation). The safety profile of nilotinib was consistent with prior studies. The most common non‐haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188).

Oral mucositis is a chief complication in patients undergoing hematopoietic stem cell transplantation (HSCT). It is considered a toxic inflammatory reaction that interferes with the patient's recuperation and quality of life. Oral candidiasis is a common fungal infection observed in dental practice, particularly in immunocompromised patients. The aim of this study was to evaluate the presence of oral mucositis and oral candidiasis in patients who underwent HSCT and their correlation with the chemotherapeutic nadir (lowest possible outcome). We evaluated patients with different diagnoses who underwent HSCT at the Hospital Erasto Gaertner. No chemotherapeutic nadir curves could be associated with mucositis, and patients had different presentations of mucositis. No patient developed oral candidiasis during hospitalization. Together with cell counts, we collected demographic data including age, oral hygiene, habits harmful to health, and the use of oral prostheses. It was observed that patients who smoked cigarettes before hospitalization showed less mucositis, resulting in no feeding problems or other comorbid conditions due to the effect of mucositis. However, the nadir of the chemotherapy curve, in isolation, is not a predictive tool for the appearance (or no appearance) of oral mucositis.