Leukemia & Lymphoma最新文献

This phase 2 study investigated pevonedistat + azacitidine + venetoclax (n = 83) versus azacitidine + venetoclax (n = 81) in patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy. The study was stopped early following negative results from PANTHER, which evaluated pevonedistat in higher-risk myelodysplastic syndromes/chronic myelomonocytic leukemia or low-blast AML. Outcomes were analyzed up to the datacut. For pevonedistat + azacitidine + venetoclax versus azacitidine + venetoclax, the median follow-up was 8.44 versus 7.95 months; the complete remission (CR) rate was 45% versus 49%; composite CR (CCR; CR+CR with incomplete blood count recovery) was 77% versus 72%. There were no differences in event-free survival (primary endpoint; hazard ratio [HR]: 0.99; 95% confidence interval [CI]: 0.61-1.60; p = 0.477) or overall survival (HR: 1.42; 95% CI: 0.82-2.49; p = 0.896). In exploratory analyses in IDH-mutated AML, CCR rates were higher with pevonedistat + azacitidine + venetoclax versus azacitidine + venetoclax. Safety was similar between treatment arms. Efficacy/safety with azacitidine + venetoclax was consistent with the phase 3 VIALE-A study.

Trial registration: NCT04266795.

Managing acute myeloid leukemia (AML) and its critical complications requires understanding the complex interplay between disease biology, treatment strategies, and patient characteristics. Complications like sepsis, acute respiratory failure (ARF), hyperleukocytosis, coagulopathy, tumor lysis syndrome (TLS) and central nervous system (CNS) involvement present unique challenges needing precise evaluation and tailored interventions. Venetoclax-induced TLS and differentiation syndrome (DS) from IDH1/IDH2 or menin inhibitors highlight the need for ongoing research and innovative approaches. As the microbiological landscape evolves and new therapeutic agents emerge, adapting strategies to mitigate harmful pharmacological interactions is crucial. Advances in understanding the genetic profiles of patients with hyperleukocytosis contribute to better-targeted therapeutic strategies. Effective AML management relies on collaborative efforts from hematologists, specialized services, and intensive care units (ICUs). This review analyzes recent data on critical AML complications, identifies areas for further investigation, and proposes ways to advance clinical research and enhance patient care strategies.

In the randomized phase III IDHENTIFY trial, the IDH2 inhibitor enasidenib (ENA) showed improvement in event-free but not overall survival compared with conventional care regimens (CCR) among patients with relapsed/refractory (R/R), IDH2-mutant AML. We constructed a partitioned survival model to evaluate the cost-effectiveness of enasidenib for the treatment of older patients with R/R, and IDH2-mutant AML. In the base-case scenario, ENA exhibited an incremental effectiveness of 0.234quality-adjusted life-years (QALYs) compared to CCR, and an incremental cost of $126,800, leading to an incremental cost-effectiveness ratio of $540,300/QALY(95% CI: $197,800-$4,777,000/QALY). In probabilistic sensitivity analysis, CCR was favored in 99.8% of simulations. The cost of ENA would need to be decreased by 72% to be cost-effective at a willingness-to-pay threshold of $150,000/QALY. Our findings suggest that ENA is unlikely to be a cost-effective treatment for older patients with IDH2-mutant R/R AML under current pricing.

New generation therapies such as bispecific antibodies (BsAb), chimeric antigen receptor T-cell therapy (CAR T) and antibody-drug conjugates (ADC) have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). However, there is emerging evidence of increased infection risk associated with these treatments in clinical trials and observational settings. This infection risk may be mediated by on-target, off-tumor side effects such as cytokine release syndrome, hypogammaglobulinaemia and cytopenias, disease-related humoral impairment and the consequences of multiple previous lines of treatment. While bacterial and viral pathogens predominate, reactivation of latent infection and opportunistic infections also warrant attention. This review characterizes the epidemiology of infections associated with novel therapies for RRMM to guide prophylaxis and antimicrobial prescribing in this patient population and highlights future areas of focus to inform ongoing infection prevention strategies.

Cancer-related cognitive impairment (CRCI) is a significant issue commonly observed following chemotherapy treatment. The study aimed to investigate the changes in cognitive function and their association with IL-6, IL-1β, and IL-10 levels before and after R-CHOP chemotherapy over six cycles. Seventy chemotherapy naïve, newly diagnosed lymphoma patients were enrolled. Cognitive functions and inflammatory cytokines were assessed at baseline (TP1), after 3rd cycle (TP2), and after 6th cycle (TP3). Patients, with mean age of 44.17 ± 13.67 years, showed significantly increased levels of IL-6 and IL-1β and decreased IL-10 levels over time (p < .001). On the Montreal Cognitive Assessment (MoCA), scores of domains such as executive functioning (p = .002), attention (p < .001), language (p < .001), recall (p = .005), and orientation (p < .001) significantly decreased post six cycles of R-CHOP chemotherapy. Correlation analysis at TP2 indicated a positive association between elevated IL-6 levels with a decrease in MoCA scores indicating a decline in cognitive function (ρ = 0.68, p < .001). At TP3, no association of MoCA scores with IL-6 and IL-1β was observed. Decreased IL-10 levels showed a weak association with decreased MoCA scores at TP2 and TP3 (ρ = 0.2, p = .09; for TP3, ρ = 0.16, p = .17), but this was not significant. In summary, the findings of the present study highlight significant cognitive decline and changes in inflammatory cytokine levels following six cycles of R-CHOP. Objective cognitive assessments may be done to detect CRCI in patients treated with R-CHOP.

Allogeneic hematopoietic stem cell transplantation (AHSCT) is currently the only treatment modality that is capable of curing myelofibrosis (MF). Although outcomes of AHSCT have improved vastly in recent years owing to advancements in HLA typing, conditioning regimens, and supportive care, it remains a procedure with a considerable risk in MF patients due to conditioning regimen related toxicity, higher rates of graft failure, infections, and graft versus host disease (GVHD). Recent progress in the treatment and prevention of GVHD with post-transplant cyclophosphamide has also rendered transplantation from alternative donors feasible and safer, thus improving access to patients without HLA-identical donors. Accordingly, all patients with intermediate or high-risk MF today should be referred for potential transplant evaluation to consider the pros and cons of an early versus a delayed transplant strategy. Individual risk assessment in MF is best facilitated by contemporary prognostic models that incorporate both clinical and genetic risk factors. The current review highlights new information regarding risk stratification in MF, anchored by practical algorithms that facilitate patient selection for specific treatment actions, including AHSCT.