Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.

PURPOSE Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. An international phase Ib/II study evaluated the safety and preliminary efficacy of venetoclax, a selective B-cell leukemia/lymphoma-2 inhibitor, together with low-dose cytarabine (LDAC) in older adults with AML. PATIENTS AND METHODS Adults 60 years or older with previously untreated AML ineligible for intensive chemotherapy were enrolled. Prior treatment of myelodysplastic syndrome, including hypomethylating agents (HMA), was permitted. Eighty-two patients were treated at the recommended phase II dose: venetoclax 600 mg per day orally in 28-day cycles, with LDAC (20 mg/m2 per day) administered subcutaneously on days 1 to 10. Key end points were tolerability, safety, response rates, duration of response (DOR), and overall survival (OS). RESULTS Median age was 74 years (range, 63 to 90 years), 49% had secondary AML, 29% had prior HMA treatment, and 32% had poor-risk cytogenetic features. Common grade 3 or greater adverse events were febrile neutropenia (42%), thrombocytopenia (38%), and WBC count decreased (34%). Early (30-day) mortality was 6%. Fifty-four percent achieved complete remission (CR)/CR with incomplete blood count recovery (median time to first response, 1.4 months). The median OS was 10.1 months (95% CI, 5.7 to 14.2), and median DOR was 8.1 months (95% CI, 5.3 to 14.9 months). Among patients without prior HMA exposure, CR/CR with incomplete blood count recovery was achieved in 62%, median DOR was 14.8 months (95% CI, 5.5 months to not reached), and median OS was 13.5 months (95% CI, 7.0 to 18.4 months). CONCLUSION Venetoclax plus LDAC has a manageable safety profile, producing rapid and durable remissions in older adults with AML ineligible for intensive chemotherapy. High remission rate and low early mortality combined with rapid and durable remission make venetoclax and LDAC an attractive and novel treatment for older adults not suitable for intensive chemotherapy.

SUMMARY Background MYC gene rearrangement (MYC-R) is present in approximately 10% of aggressive B-cell lymphomas with approximately half harboring a BCL2 gene rearrangement (BCL2-R). Multiple retrospective studies of R-CHOP show an inferior outcome in patients with MYC-R, both alone and with BCL2-R and/or BCL6-R, and suggest better outcomes with more aggressive treatment. In the current study, we aimed to determine the outcome of DA-EPOCH-R, an aggressive infusional treatment regimen, in untreated MYC-R aggressive B-cell lymphomas. Methods Final analysis of a prospective multi-center study of DA-EPOCH-R (dose-adjusted treatment: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituxiomab) in 53 patients with untreated MYC-R aggressive B-cell lymphomas. DAEPOCH-R was scheduled to be administered with central nervous system prophylaxis for 6 cycles. Primary endpoints included event-free and overall survival. The study was registered at ClinicalTrials.gov (NCT01092182). Findings Patient characteristics included median age 61 (range 29–80) years, stage III/IV disease in 43 (81%), and high-intermediate/high international prognostic score (IPI) in 26 (49%) patients. Characteristics were similar among patients with confirmed MYC-R single-hit (n=19) versus those with a BCL2-R and/or BCL6-R, termed double-hit, (n=24) lymphomas. With a median follow up of 55.6 (Interquartile range: 50.5–61.1) months, the 48-month EFS and OS for all patients was 71% and 77%, respectively, with no differences among patients with single versus double-hit tumors or age < versus ≥ 60 years. The EFS at 48-months for low/low-intermediate (0–2) versus high-intermediate/high (3–5) IPI was 89% versus 50%, respectively, for all patients, and 92% versus 55% for double-hit patients. Toxicity included grade 4 neutropenia and thrombocytopenia on 53% and 13% of cycles, respectively, and fever with neutropenia occurred on 19% of cycles. There were 3 treatment related deaths. Interpretation In this study, DA-EPOCH-R produced durable remissions in MYC-R aggressive B-cell lymphomas and should be considered for the treatment of these diseases. Funding Cancer Trials Support Unit and Center for Cancer Research, National Cancer Institute, USA, and Genentech Inc.

Learning Objectives After completing this course, the reader will be able to: Outline the five steps that comprise shared decision making. Identify specific tactics that can be used to engage a patient in a shared decision making process. This article is available for continuing medical education credit at http://CME.TheOncologist.com Background. There is growing interest by patients, policy makers, and clinicians in shared decision making (SDM) as a means to involve patients in health decisions and translate evidence into clinical practice. However, few clinicians feel optimally trained to implement SDM in practice, and many patients report that they are less involved than they desire to be in their cancer care decisions. SDM might help address the wide practice variation reported for many preference‐sensitive decisions by incorporating patient preferences into decision discussions. Methods. This paper provides a perspective on how to incorporate SDM into routine oncology practice to facilitate patient‐centered communication and promote effective treatment decisions. Oncology practice is uniquely positioned to lead the adoption of SDM because of the vast number of preference‐sensitive decisions in which SDM can enhance the clinical encounter. Results. Clinicians can facilitate cancer decision making by: (a) determining the situations in which SDM is critical; (b) acknowledging the decision to a patient; (c) describing the available options, including the risks, benefits, and uncertainty associated with options; (d) eliciting patients' preferences; and (e) agreeing on a plan for the next steps in the decision‐making process. Conclusion. Given recent policy movements toward incorporating SDM and translating evidence into routine clinical practice, oncologists are likely to continue expanding their use of SDM and will have to confront the challenges of incorporating SDM into their clinical workflow. More research is needed to explore ways to overcome these challenges such that both quality evidence and patient preferences are appropriately translated and incorporated into oncology care decisions.