® ASH NEWS AND REPORTS JULY/AUGUST 2017 VOLUME 14 ISSUE 4 DIFFUSION FEATURE More Than an Aspirin a Day to Keep Disparities of Adolescent and Young Adult Patients in Recurrent Venous Thromboembolism Away the Treatment of Malignant Hematologic Diseases Weitz JI, Lensing AWA, Prins MH, et al. Rivaroxaban or aspirin for LEIDY L. ISENALUMHE, MD, MS extended treatment of venous thromboembolism. N Engl J Med. 2017;376:1211-1222. Adult Clinical Hematology-Oncology Fellow, H. Lee Moffitt Cancer Center and Research Institute; Pediatric Hematologist/ Oncologist; Chair, ASH Trainee Council; Tampa, FL hether to extend anticoagulant therapy for a deep The Adolescent and Young Adult (AYA) Progress Review Group (PRG) defines the vein thrombosis or pulmonary embolism beyond the AYA cancer population as patients ranging from 15 to 39 years of age. An estimated acute treatment period can be a problematic decision. 69,000 AYA individuals are diagnosed with cancer each year — six times more than Anticoagulant therapy reduces the risk of recurrent venous children younger than 14 years.1 The AYA age demarcation was established as a Wthromboembolic events (VTE), but at the cost of an increased risk of high-risk population after data from the Surveillance, Epidemiology, and End Results 1-3 bleeding. Reducing the intensity of anticoagulant therapy or switching (SEER) study showed a lack in improvement in survival for patients with many forms 3 to aspirin have both been proposed as options in patients who wish of cancer.2,3 The most common malignancies are leukemia, lymphoma, germ cell tumors, and central to continue protection, but the efficacy and safety of these strategies is nervous system tumors among 15 to 24 year olds, with the incidence of breast cancer, colorectal still uncertain. cancer, and melanoma increasing among older AYA patients1 (Figure). Dr. Jeffrey I. Weitz and colleagues reported the results of a double- blind, randomized controlled trial, “EINSTEIN CHOICE,” which Figure Common Types of Cancer Affecting AYAs compared rivaroxaban 10 mg daily (low intensity) with rivaroxaban 20 mg daily (standard intensity) and aspirin 100 mg daily for prevention of recurrent VTE. All 3,365 randomly assigned patients received six to 12 months of anticoagulant therapy prior to enrollment. Patients with provoked or unprovoked VTE were eligible as long as their clinician believed there was uncertainty about the value of long-term treatment. Study duration was up to 12 months. The primary efficacy outcome measure was symptomatic fatal or nonfatal recurrent VTE, and the primary safety outcome was major bleeding. The results showed that the rivaroxaban 20-mg and 10-mg doses were both superior to aspirin for the prevention of recurrent VTE (rivaroxaban 20 mg, 1.5%; rivaroxaban 10 mg, 1.2%; aspirin, 4.4%; HR [rivaroxaban 20 mg vs. aspirin], 0.34; 95% CI, 0.20-0.59; p<0.001; HR [rivaroxaban 10 mg vs. aspirin], 0.26; 95% CI, 0.14-0.47; p<0.001). Between the two doses of rivaroxaban, there was no difference in the risk of recurrence (HR, 1.34; 95% CI, 0.65-2.75; p=0.42) or the risk of major bleeding (0.5% and 0.4%, respectively). Furthermore, the risk of major bleeding in both rivaroxaban arms was similar to aspirin (0.3%). The risk of clinically relevant nonmajor bleeding was not significantly different across the three groups (rivaroxaban 10 mg, 2.0%; rivaroxaban 20 mg, 2.7%; aspirin, 1.8%). There are important limitations to this study that should be considered. First, the total number of events (80) was small. This is likely due to the substantial proportion of patients with provoked VTE enrolled in *includes testicular cancer. **includes breats, cervical, colon and other less prevalent cancers. ***includes malignant bone tumors and other less prevalent cancers. the study (60%). This group is known to have a low risk of recurrence Adapted from1 A Snapshot of Adolescent and Young Adult Cancers: National Cancer Institute. [cited 2015 Nov 28]; NCI Surveillance, Epidemiology, and End without anticoagulant therapy; therefore their inclusion in the study is Results (SEER) Program. Data is from SEER 18, 2007-2011, ages 15-39. Available from: www.cancer.gov/research/progress/snapshots/adolescent-young-adult. controversial.5 Additionally, the duration of treatment was limited to one year. Patients facing this choice are deciding if they should continue In 2007, the AYA PRG released a comprehensive guide explaining the disparities experienced by AYA anticoagulation indefinitely, which can mean decades of treatment. cancer patients that have led to their poor outcomes and lack of progress throughout the years.2 Lastly, the study was not powered to determine if 10 mg of rivaroxaban These disparities include lack of health insurance, differences in is noninferior to 20 mg with respect to efficacy. Table 1: List of the disease biology, delay of diagnosis and treatment, increased toxicities, Disparities Experienced lower socioeconomic status,4 and overall lack of awareness in the Overall, the results of the EINSTEIN CHOICE study show that even by AYA Hematology- medical field as to the special needs of this population (Table 1). low-dose anticoagulation is superior to aspirin, and without a higher oncology Patients price to pay with respect to bleeding. Consequently, the key message The goal of the AYA PRG was not only to introduce and educate of this trial is that patients who wish to continue protection from Access to health care the medical field about this high-risk population, but also to start recurrent VTE have little to gain by switching to aspirin. However, what Psychosocial stressors this study cannot do is confirm that rivaroxaban 10 mg once daily is a systematic mitigation of the disparities. Since the release of sufficient for patients with a high risk of recurrence. Delay in diagnosis the PRG guide, progress has been made, including an increase in AYA-specific scientific peer review publications, formation of AYA Delay in treatment 1. Kearon C, Ginsberg JS, Kovacs MJ, et al. Comparison of low-intensity warfarin therapy oncology programs, development of AYA-specific national workshops with conventional-intensity warfarin therapy for long-term prevention of recurrent venous Treatment site and committees, development of clinical trials targeting AYAs, and thromboembolism. N Engl J Med. 2003;349:631-639. expansion of inclusion criteria to include AYAs.4,5 Additionally, the 2. Ridker PM, Goldhaber SZ, Glynn RJ. Low-intensity versus conventional-intensity Reduced rates of clinical warfarin for prevention of recurrent venous thromboembolism. N Engl J Med. European Cancer Registry (EUROCARE) and NCI SEER data have 2003;349:2164-2167. trial enrollment and 5,6 reported improvement in survival rates for the AYA population. 3. Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous treatment standardization thromboembolism. N Engl J Med. 2013;368:699-708. Despite some improvement in survival, AYAs still have lower five- 4. Simes J, Becattini C, Agnelli G, et al. Aspirin for the prevention of recurrent venous Increased toxicity year relative survival rates for acute lymphoblastic leukemia (ALL), thromboembolism: the INSPIRE collaboration. Circulation. 2014;130:1062-1071. acute myeloid leukemia (AML), rhabdomyosarcoma, Ewing sarcoma, 5. Iorio A, Kearon C, Filippucci E, et al. Risk of recurrence after a first episode of and breast cancer compared with children and older adults.6 Notably, the incidence of all invasive symptomatic venous thromboembolism provoked by a transient risk factor: a systematic 7 review. Arch Intern Med. 2010;170:1710-1716. cancers continues to increase in AYAs compared with any other age group. Although many common malignancies overlap in younger and older patients, research advances LORI-ANN LINKINS, MD, MSC (CLIN EPI), FRCPC in ALL, breast cancer, colorectal cancer, sarcoma, and melanoma have identified age-dependent Dr. Linkins indicated no relevant conflicts of interest. (Cont. on page 2) PRESIDENT’S COLUMN – ASK THE HEMATOLOGIST – MINI REVIEW – Contributing Editor PROFILES – Dr. Jack Hirsh reflects on a 2 Dr. Ken Anderson outlines six strategic 4 Dr. John Hausdorff gives his take on the 5 Dr. Omar Abdel-Wahab summarizes key 6 life devoted to hematology; mentee Dr. John priorities for the Society. SPIKES protocol for conveying bad news. findings related to histiocytoses. Kelton pays tribute. PRESIDENT’S COLUMN HTHE ematologist ASH NEWS AND REPORTS® ISSN 1551-8779 PUBLISHED BIMONTHLY Editor-in-Chief: Beyond Business As Usual Jason Gotlib, MD, MS n May of this year, ASH held its yearly Executive Committee Spring Retreat, in Quebec City, Canada, where Executive Committee Stanford Cancer Institute members and senior staff have an opportunity to collaborate, bond, and be inspired by our diverse points of view. This year, there Stanford, CA I emerged the beginnings of some major strategic initiatives and goals for ASH to develop further in the coming months and years. These Contributing Editors: initiatives demonstrate ASH’s constant growth and commitment to improvement in the field of hematology. Omar Abdel-Wahab, MD Memorial Sloan-Kettering Cancer Center ASH realizes that there is a need to facilitate the sharing of high-quality clinical data for ASH members and the hematology community, New York, NY and to provide direct data management support for disease-specific research activities. Thus, ASH has committed to developing its own data registry focusing initially on sickle cell disease (SCD) and multiple myeloma. And given our ongoing efforts to conquer SCD, ASH Michael DeBaun, MD continues to take on new ways to equip hematologists with the tools and knowledge they need to best serve SCD patients. For example, Vanderbilt University ASH is exploring the development of a clinical trials network for SCD to help clinical research sites develop and test interventional Nashville, TN therapeutics that may improve SCD patient outcomes. Tracy I. George, MD University of New Mexico Another takeaway is the impressive work of ASH’s standing committees.