ASH Clinical News ACN_5.2_digital | Page 35

CLINICAL NEWS [p value not provided].” “Because of its positive impact on anemia, clinical events, and quality of life, hydroxyurea can now be considered for routine care of children with SCA in Africa,” Dr. Tshilolo concluded. The study’s implications are limited by the single-arm design, and Dr. Tshilolo noted that the costs of hydroxyurea treatment and associated laboratory monitoring will be a major factor limiting more widespread use of the drug to treat SCA in Africa. “The current cost of treatment is beyond the daily wage of most families living in sub-Saharan Africa,” he said. However, REACH participants received the hydroxy- urea capsules, all lab tests, and transportation to clinic visits at no charge, which may have contrib- uted to the high rates of retention and adherence to treatment on the study. “We hope that treatment will be made available to more patients through outside financial support, as is the case with treat- ment for HIV infection in several African countries.” The authors report financial relationships with Addmedica, the manufacturers of hydroxyurea, and Bristol-Myers Squibb, which provided funding for the trial. REFERENCE Tshilolo L, Tomlinson G, Williams TN, et al. Realizing effectiveness across continents with hydroxyurea (REACH): a prospective multi-national trial of hydroxyurea for sickle cell anemia in sub-Saharan Africa. Abstract #3. Presented at the 2018 ASH Annual Meeting, December 2, 2018; San Diego, CA. REVLIMID [lenalidomide] capsules, for oral use Table 7: Grade 3/4 Adverse Reactions Reported in ≥2% Patients and With a ≥1% Difference in Proportion of Patients Between the REVLIMID/dexamethasone and Placebo/dexamethasone groups Body System Adverse Reaction REVLIMID/Dex & (N=353) n (%) Placebo/Dex & (N=350) n (%) 12 ( 3.4) Febrile Neutropenia % 43 ( 12.2) 22 ( 6.3) Vascular disorders 35 ( 9.9) 20 ( 5.7) 118 ( 33.4) Thrombocytopenia @ Anemia @ Leukopenia 14 ( 4.0) 1 ( 0.3) Lymphopenia 10 ( 2.8) 4 ( 1.1) 8 ( 2.3) 0 ( 0.0) Febrile Neutropenia % General disorders and administration site conditions Fatigue 23 ( 6.5) 17 ( 4.9) Vascular disorders Deep vein thrombosis % REVLIMID/Dex & (N=353) n (%) Body System Adverse Reaction Deep vein thrombosis % Pneumonia @ 12 ( 3.4) Pulmonary embolism @ Atrial fibrillation @ Gastrointestinal disorders 19 ( 5.4) 1 ( 0.3) Metabolism and nutrition disorders Hypokalemia 17 ( 4.8) 5 ( 1.4) Hypocalcemia 13 ( 3.7) 6 ( 1.7) 9 ( 2.5) 0 ( 0.0) Hypophosphatemia Respiratory, thoracic and mediastinal disorders Pulmonary embolism @ Respiratory Distress @ 14 ( 4.0) 3 ( 0.9) 4 ( 1.1) 0 ( 0.0) Musculoskeletal and connective tissue disorders Muscle weakness 20 ( 5.7) 10 ( 2.9) Gastrointestinal disorders Diarrhea @ 11 ( 3.1) 4 ( 1.1) Constipation 7 ( 2.0) 1 ( 0.3) Nausea @ 6 ( 1.7) 2 ( 0.6) 13 ( 3.7) 4 ( 1.1) Cardiac disorders Atrial fibrillation @ Tachycardia 6 ( 1.7) 1 ( 0.3) Cardiac Failure Congestive @ 5 ( 1.4) 1 ( 0.3) Syncope 10 ( 2.8) 3 ( 0.9) Dizziness 7 ( 2.0) 3 ( 0.9) Cataract 6 ( 1.7) 1 ( 0.3) Cataract Unilateral 5 ( 1.4) 0 ( 0.0) 10 ( 2.8) 6 ( 1.7) Nervous System disorders Eye Disorders Psychiatric Disorder Depression Cosmos Communications 11 ( 3.1) 33 ( 9.3) 21 ( 6.0) 13 ( 3.7) 3 ( 0.9) 11 ( 3.1) 2 ( 0.6) 5 ( 1.4) 0 ( 0.0) 7 ( 2.0) 3 ( 0.9) 6 ( 1.7) 2 ( 0.6) 4 ( 1.1) 0 ( 0.0) Nervous system disorders Cerebrovascular accident @ 5 ( 1.4) 26 ( 7.4) Cardiac disorders Pneumonia @ 30 ( 8.5) 0 ( 0.0) Respiratory, thoracic, and mediastinal disorders Cardiac Failure Congestive @ 29 ( 8.2) 6 ( 1.7) Infections and infestations Infections and infestations Urinary Tract Infection Placebo/Dex & (N=350) n (%) Blood and lymphatic system disorders Blood and lymphatic system disorders Neutropenia % Table 8: Serious Adverse Reactions Reported in ≥1% Patients and With a ≥1% Difference in Proportion of Patients Between the REVLIMID/dexamethasone and Placebo/dexamethasone Groups Diarrhea @ Musculoskeletal and connective tissue disorders Bone Pain For Tables 6, 7 and 8 above: @ - adverse reactions in which at least one resulted in a fatal outcome % - adverse reactions in which at least one was considered to be life threatening (if the outcome of the reaction was death, it is included with death cases) Median duration of exposure among patients treated with REVLIMID/ dexamethasone was 44 weeks while median duration of exposure among patients treated with placebo/dexamethasone was 23 weeks. This should be taken into consideration when comparing frequency of adverse reactions between two treatment groups REVLIMID/dexamethasone vs. placebo/dexamethasone. Venous and Arterial Thromboembolism [see Boxed Warning, Warnings and Precautions (5.4)] VTE and ATE are increased in patients treated with REVLIMID. Deep vein thrombosis (DVT) was reported as a serious (7.4%) or severe (8.2%) adverse drug reaction at a higher rate in the REVLIMID/ dexamethasone group compared to 3.1 % and 3.4% in the placebo/ dexamethasone group, respectively in the 2 studies in patients with at least 1 prior therapy with discontinuations due to DVT adverse reactions reported at comparable rates between groups. In the NDMM study, DVT was reported as an adverse reaction (all grades: 10.3%, 7.2%, 4.1%), as a serious adverse reaction (3.6%, 2.0%, 1.7%), and as a Grade 3/4 adverse reaction (5.6%, 3.7%, 2.8%) in the Rd Continuous, Rd18, and MPT Arms, respectively. Discontinuations and dose reductions due to DVT adverse reactions were reported at comparable rates between the Rd Continuous and Rd18 Arms (both <1%). Interruption of REVLIMID treatment due to DVT adverse reactions was reported at comparable rates between the Rd Continuous (2.3%) and Rd18 (1.5%) arms. Pulmonary embolism (PE) was reported as a serious adverse drug reaction (3.7%) or Grade 3/4 (4.0%) at a higher rate in the REVLIMID/ dexamethasone group compared to 0.9% (serious or grade 3/4) in the placebo/dexamethasone group in the 2 studies in patients with, at least 1 prior therapy, with discontinuations due to PE adverse reactions reported at comparable rates between groups. In the NDMM study, the frequency of adverse reactions of PE was similar between the Rd Continuous, Rd18, and MPT Arms for adverse reactions (all grades: 3.9%, 3.3%, and 4.3%, respectively), serious adverse reactions (3.8%, 2.8%, and 3.7%, respectively), and grade 3/4 adverse reactions (3.8%, 3.0%, and 3.7%, respectively). 1 Q1 Q2