Venetoclax is a BCL-2 inhibitor that effectively improves clinical outcomes in newly diagnosed, relapsed and refractory acute myeloid leukemia (AML) patients, with complete response rates (with and without complete blood count recovery) ranging between 34–90% and 21–33%, respectively. Here, we aim to give an overview of the efficacy of venetoclax-based therapy for AML patients, as compared to standard chemotherapy, and on factors and mechanisms involved in venetoclax sensitivity and resistance in AML (stem) cells, with the aim to obtain a perspective of response biomarkers and combination therapies that could enhance the sensitivity of AML cells to venetoclax. The presence of molecular aberrancies can predict responses to venetoclax, with a higher response in NPM1-, IDH1/2-, TET2- and relapsed or refractory RUNX1-mutated AML. Decreased sensitivity to venetoclax was observed in patients harboring FLT3-ITD, TP53, K/NRAS or PTPN11 mutations. Moreover, resistance to venetoclax was observed in AML with a monocytic phenotype and patients pre-treated with hypomethylating agents. Resistance to venetoclax can arise due to mutations in BCL-2 or pro-apoptotic proteins, an increased dependency on MCL-1, and usage of additional/alternative sources for energy metabolism, such as glycolysis and fatty acid metabolism. Clinical studies are testing combination therapies that may circumvent resistance, including venetoclax combined with FLT3- and MCL-1 inhibitors, to enhance venetoclax-induced cell death. Other treatments that can potentially synergize with venetoclax, including MEK1/2 and mitochondrial complex inhibitors, need to be evaluated in a clinical setting.

Background: With the global rise in chronic health conditions, health care is transforming, and patient empowerment is being emphasized to improve treatment outcomes and reduce health care costs. Patient-centered innovations are needed. We focused on patients with chronic myeloid leukemia (CML), a chronic disease with a generally good long-term prognosis because of the advent of tyrosine kinase inhibitors. However, both medication adherence by patients and guideline adherence by physicians are suboptimal, unnecessarily jeopardizing treatment outcomes. Objective: The aim of this study was to develop a patient-centered innovation for patients with CML using a design thinking methodology. Methods: The 5 phases of design thinking (ie, empathize, define, ideate, prototype, and test) were completed, and each phase started with the patient. Stakeholders and end users were identified and interviewed, and observations in the care system were made. Using tools in human-centered design, problems were defined and various prototypes of solutions were generated. These were evaluated by patients and stakeholders and then further refined. Results: The patients desired (1) insights into their own disease; (2) insights into the symptoms experienced, both in terms of knowledge and comprehension; and (3) improvements in the organization of care delivery. A web-based platform, CMyLife, was developed and pilot-tested. It has multiple features, all targeting parts of the bigger solution, including a website with reliable information and a forum, a guideline app, personal medical records with logs of symptoms and laboratory results (including a molecular marker and linked to the guideline app), tailored feedback based on the patients’ symptoms and/or results, screen-to-screen consulting, delivery of medication, and the collection of blood samples at home. Conclusions: The multifeatured innovation, CMyLife, was developed in a multidisciplinary way and with active patient participation. The aim of developing CMyLife was to give patients the tools to monitor their results, interpret these results, and act on them. With this tool, they are provided with the know-how to consider their results in relation to their personal care process. Whether CMyLife achieves its goal and the evaluation of the added value will be the focus of future studies. CML could become the first malignancy for which patients are able to monitor and manage their disease by themselves.

Purpose of Review: Treatment of elderly patients with acute myeloid leukemia is a known challenge for hematologists due to patient diversity, heterogeneous disease biology, and a rapidly evolving treatment landscape. Here, we highlight the importance of determining fitness, review the latest therapeutic developments, and discuss clinical scenarios to provide guidance on individualized treatment for older AML patients. Recent Findings: Several factors, like age, performance status, and comorbidities, play a role in fitness and are associated with outcome. Comorbidity scoring systems and geriatric assessments are tools to help physicians select the most appropriate treatment for each patient. The addition of venetoclax, targeted therapy with IDH1/2 and FLT3 inhibitors, and enhanced formulas of existing drugs like CPX-351 and oral azacitidine have improved responses and outcomes. Summary: New drugs and combination therapies have increased the therapeutic options for elderly AML patients but determination of fitness and disease biology is essential to select patient-tailored treatments.