Evaluating the Impact of a Switch to Nilotinib on Imatinib-Related Chronic Low-Grade Adverse Events in Patients With CML-CP: The ENRICH Study

AbstractBackgroundMany patients with chronic myeloid leukemia in chronic phase experience chronic treatment-related adverse events (AEs) during imatinib therapy. These AEs can impair quality of life and lead to reduced treatment adherence, which is associated with poor clinical outcomes.Patients and MethodsIn the phase II ENRICH (Exploring Nilotinib to Reduce Imatinib Related Chronic Adverse Events) study (N = 52), the effect of switching patients with imatinib-related chronic low-grade nonhematologic AEs from imatinib to nilotinib was evaluated.ResultsThree months after switching to nilotinib, 84.6% of the patients had overall improvement in imatinib-related AEs (primary endpoint). Of 210 imatinib-related AEs identified at baseline, 62.9% had resolved within 3 months of switching to nilotinib. Of evaluable patients, most had improvements in overall quality of life after switching to nilotinib. At screening, 65.4% of evaluable patients had a major molecular response (BCR-ABL1 ≤ 0.1% on the International Scale). After switching to nilotinib, the rate of the major molecular response was 76.1% at 3 months and 87.8% at 12 months. Treatment-emergent AEs reported with nilotinib were typically grade 1 or 2; however, some patients developed more serious AEs, and 8 patients discontinued nilotinib because of new or worsening AEs.ConclusionOverall, results from the ENRICH study demonstrated that switching to nilotinib can mitigate imatinib-related chronic low-grade nonhematologic AEs in patients with chronic myeloid leukemia in chronic phase, in conjunction with acceptable safety and achievement of molecular responses. This trial was registered at www.clinicaltrials.gov as NCT00980018

Phase 2 study of everolimus for relapsed or refractory classical Hodgkin lymphoma

Abstract Background The current standard of care for classical Hodgkin lymphoma (HL) is multiagent chemotherapy with or without radiation. In patients who relapse or fail to respond, additional high-dose chemotherapy with autologous hematopoietic stem cell transplantation (AHSCT) can improve progression-free survival (PFS). Novel therapies are required for patients refractory to chemotherapy and AHSCT. The mammalian target of rapamycin inhibitor everolimus has shown preliminary activity in preclinical models of HL and promising efficacy in patients with relapsed or refractory HL. Methods This was an open-label, two-stage, phase 2 study that enrolled 57 patients aged ≥ 18 years with classic HL that had progressed after standard therapy. Patients received everolimus 10 mg daily until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision. The primary endpoint was overall response rate; secondary endpoints included PFS, overall survival, time to response, duration of response, and safety. Results Overall response rate was 45.6% (95% confidence interval [CI] 32.4–59.3%); five patients (8.8%) experienced a complete response and 21 patients had a partial response (36.8%). Median PFS was 8.0 months (95% CI 5.1–11.0 months). Seven patients (12%) were long-term responders (≥ 12 months). The most common study drug-related adverse events were thrombocytopenia (45.6%), fatigue (31.6%), anemia (26.3%), rash (24.6%), and stomatitis (22.8%). Conclusions Everolimus 10 mg/day demonstrated favorable results in patients with heavily pretreated, relapsed, or refractory classical HL. These findings support the further evaluation of everolimus in this indication. Trial registration ClinicalTrials.gov NCT01022996. Registered November 25, 200

Fabrication of nickel foam supported Cu-doped Co3O4 nanostructures for electrochemical energy storage applications

In this study, we have synthesized hierarchical nano-discs of Cu doped Co3O4 (Cu·Co3O4) and decorated them directly on the 3D nickel foam (NF) via single-step urea assisted hydrothermal method. The crystal structure and elemental composition of the fabricated sample were examined using PXRD, Raman, and EDX analyses. The morphology, particle size, and structure of the fabricated sample were evaluated by FESEM analysis. I–V experiments showed that the Cu·Co3O4 samples exhibited higher conductivity (8.73 × 10−3 Sm−1) than the un-doped sample (6.42 × 10−5 Sm−1). The electrochemical investigation revealed that Cu·Co3O4@NF electrode displayed a higher specific capacitance of 728 F/g @1 A/g and exceptional cyclic activity, as after 6000 electrochemical cyclic tests it retains 98.3% of its initial specific capacitance. In comparison, the undoped Co3O4@NF electrode showed inferior electrochemical aptitude as it exhibited 566 F/g specific capacitance @1 A/g and holds just 60.2% of its initial capacitance after 6000 electrochemical tests. Additionally, on increasing the applied current density from 1 A/g to 7 A/g the Cu·Co3O4@NF electrode showed a lower capacity fade of 16%, indicating its excellent rate capability. The integrated electrochemical features (good rate capability, specific capacitance, and superior cyclic activity) of the Cu·Co3O4@NF sample were attributed to its superb electrical conductivity (8.73 × 10−3 Sm−1), binder-free design, 2D morphology, porous nature, and hierarchical structure. The synergistic effects among the acquired novel features of the doped sample not only enhanced its exposed surface area, but also buffered the Cu·Co3O4 samples from pulverization, volume expansion, and agglomeration during the electrochemical investigations

Bifunctional electrocatalytic water splitting augmented by cobalt-nickel-ferrite NPs-supported fluoride-free MXene as a novel electrocatalyst

Electrocatalytic water splitting is a promising approach for the massive production of hydrogen as an environmentally compatible and renewable energy alternative to fossil fuels. The development of an active, stable, low-cost, and bifunctional electrocatalyst, in this regard, is a big challenge to achieve the desired electrocatalytic hydrogen/oxygen production via water splitting. MXene (Ti3C2Tx) has recently been explored as an excellent candidate for electrocatalytic water splitting. However, its poor stability, hazardous synthesis routes, and the restacking of its flakes are the major bottlenecks in its effective application as an electrocatalyst. Herein, we adopted an acid-free wet chemical approach to synthesize MXene and its composites with CoNiFe2O4 for efficient water splitting. We proposed a novel layer-by-layer (LBL) assembly approach to obtain a CoNiFe2O4/MXene-based 2D/NPs/2D network and prevented restacking in MXene flakes for efficient electrocatalysis. The inserted NPs via the LBL approach engaged the delaminated MXene flakes, which results in a high surface area and active sites for water splitting. The fabricated catalyst showed excellent overpotentials of 149 and 17 mV at 10 mA/cm2 for water splitting via OER and HER. In addition, the Tafel slope of 36 and 45 mV/dec was achieved for HER and OER along with high electrochemical stability upto 100 h, which surpassed many similar catalysts that were recently reported in the literature. This study provides insights into the design of multicomponent low-dimensional electrocatalysts for water splitting. Copyright © 2023 Elsevier B.V.11Nsciescopu