Saliba, Antoine N

SummaryAmong 301 newly diagnosed patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent, 23 (7.6%) experienced major cardiac complications: 15 cardiomyopathy, 5 non‐ST elevation myocardial infarction and/or 7 pericarditis/effusions. Four patients had more than one cardiac complication. Baseline characteristics included median age ± interquartile range; 73 ± 5 years; 87% males; 96% with cardiovascular risk factors; and 90% with preserved baseline ejection fraction. In multivariate analysis, males were more likely (p = 0.02) and DNMT3A‐mutated cases less likely (p < 0.01) to be affected. Treatment‐emergent cardiac events were associated with a trend towards lower composite remission rates (43% vs. 62%; p = 0.09) and shorter survival (median 7.7 vs. 13.2 months; p < 0.01). These observations were retrospectively retrieved and warrant further prospective examination.

Abstract Venetoclax + hypomethylating agent (Ven‐HMA) is currently the standard frontline therapy for older/unfit patients with newly diagnosed acute myeloid leukemia (ND‐AML). Our objective in the current retrospective study of 301 adult patients (median age 73 years; 62% de novo) with ND‐AML was to identify molecular predictors of treatment response to Ven‐HMA and survival; European LeukemiaNet (ELN) genetic risk assignment was favorable 15%, intermediate 16%, and adverse 69%. Complete remission, with (CR) or without (CRi), count recovery, was documented in 182 (60%) patients. In multivariable analysis, inclusive of mutations only, “favorable” predictors of CR/CRi were NPM1 (86% vs. 56%), IDH2 (80% vs. 58%), and DDX41 (100% vs. 58%) and “unfavorable” TP53 (40% vs. 67%), FLT3‐ ITD (36% vs. 63%), and RUNX1 (44% vs. 64%) mutations; significance was sustained for each mutation after adjustment for age, karyotype, and therapy‐related qualification. CR/CRi rates ranged from 36%, in the presence of unfavorable and absence of favorable mutation, to 91%, in the presence of favorable and absence of unfavorable mutation. At median follow‐up of 8.5 months, 174 deaths and 41 allogeneic stem cell transplants (ASCT) were recorded. In multivariable analysis, risk factors for inferior survival included failure to achieve CR/CRi (HR 3.4, 95% CI 2.5–4.8), adverse karyotype (1.6, 1.1–2.6), TP53 mutation (1.6, 1.0–2.4), and absence of IDH2 mutation (2.2, 1.0–4.7); these risk factors were subsequently applied to construct an HR‐weighted risk model that performed better than the ELN genetic risk model (AIC 1661 vs. 1750): low ( n = 130; median survival 28.9 months), intermediate ( n = 105; median 9.6 months), and high ( n = 66; median 3.1 months; p < .001); survival in each risk category was significantly upgraded by ASCT. The current study identifies genotype signatures for predicting response and proposes a 3‐tiered, CR/CRi‐based, and genetics‐enhanced survival model for AML patients receiving upfront therapy with Ven‐HMA.

AbstractThe intricate interplay of anemia and iron overload under the pathophysiological umbrella of ineffective erythropoiesis in non-transfusion-dependent β-thalassemia (NTDT) results in a complex variety of clinical phenotypes that are challenging to diagnose and manage. In this article, we use a clinical framework rooted in pathophysiology to present 4 common scenarios of patients with NTDT. Starting from practical considerations in the diagnosis of NTDT, we delineate our strategy for the longitudinal care of patients who exhibit different constellations of symptoms and complications. We highlight the use of transfusion therapy and novel agents, such as luspatercept, in the patient with anemia-related complications. We also describe our approach to chelation therapy in the patient with iron overload. Although tackling every specific complication of NTDT is beyond the scope of this article, we touch on the management of the various morbidities and multisystem manifestations of the disease.

AbstractBackgroundAlthough the clinical outcomes of patients with TP53‐mutated acute myeloid leukemia (AML) are dismal, subsets of patients eligible for curative‐intent therapies may fare better. Because racial disparities are known to affect outcome in hematologic malignancies, the authors sought to explore disparities among patients with TP53‐mutated AML.MethodsA multicenter, retrospective study was conducted in a cohort of 340 patients who had TP53‐mutated AML (275 non‐Hispanic White [NHW] and 65 non‐Hispanic Black [NHB]) to analyze differences in treatment and outcome among NHW and NHB patients.ResultsThe median patient age was comparable between NHW and NHB patients (p = .76). A higher proportion of NHB patients had therapy‐related AML (31% vs. 20%; p = .08) and had co‐mutations (74% vs. 61%; p = .06). A higher proportion of NHW patients received intensive chemotherapy compared with NHB patients (47% vs. 31%; p = .02). Conversely, a higher proportion of NHB patients received low‐intensity chemotherapy (9% vs. 5.5%; p = .02) or best supportive care (22% vs. 7%; p < .001). The complete response rate (including complete responses with or without complete count recovery) was 31% versus 24.5% (p = .39) in NHW and NHB patients, respectively. Only 5% of NHB patients received allogeneic stem cell transplantation compared with 15.5% of NHW patients (p = .02). The proportion of patients who were event‐free (18.5% vs. 8.5%; p = .49) or who remained alive (24.9% vs. 8.3%; p = .13) at 18 months was numerically higher in NHW versus NHB patients, respectively, but was not statistically significant.ConclusionsThe current study highlights disparities between NHW and NHB patients with TP53‐mutated AML. Efforts are warranted to eliminate treatment disparities in minority populations.

Key points Psycho‐oncology, a multidisciplinary field that addresses the patients' and their caregivers' physical, psychological, social, and behavioral well‐being, is extensively integrated in cancer care in high‐income countries Psycho‐oncology services remain underdeveloped, fragmented, and poorly implemented in low‐ and middle‐income countries, particularly those in the Arab Middle East and North Africa region To upgrade these services, accommodation to both (i) the unique needs of Arab low‐ and middle‐income countries and (ii) the best practices of psycho‐oncology is crucial There is scarcity of research on the barriers and challenges faced during building or expanding psycho‐oncology services in the Arab low‐ and middle‐income countries We summarize a priori challenges that may be encountered in psychosocial capacity building in similar Arab low‐ and middle‐income countries using Lebanon as a pilot program