Clinical Lymphoma, Myeloma & Leukemia, Vol.20, Suppl.1 - September 2020

Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2020 S232 PT search results. The AC was blind to dose, dose modification, and investigator causality opinion. Events not associated with a cardiovascular etiology or that failed to meet the ACC/AHA, FDA, and SCTI definitions were determined by the AC not to be AOEs. Results: This review included all 449 heavily pretreated patients with Ph+ leukemia enrolled in PACE (median age, 59 y; 47% female; 93%  2 tyrosine kinase inhibitors). At a median follow-up of 37.3 months, adjudicated AOEs occurred in 17.4% of the overall patient population compared with 24.7% pre-adjudication. The majority of the pre-adjudication serious AOEs were adjudicated as serious AOEs (20% pre-adjudication vs 16% adjudicated). The most common adjudicated AOE (>2%) was peripheral arterial occlusive disease. Exposure-adjusted incidence of newly occurring adjudicated AOEs decreased over time. Analyses by baseline risk factors demonstrated that patients with the following baseline risk factors had higher incidence rates of adjudicated AOEs than those without ischemic cardiac disease, hypertension, hypercholesterolemia, and diabetes. Conclusions: Independent AC review of the PACE trial identified a lower rate of clinically relevant AOEs than previously reported, suggesting an earlier possible overestimation that may not accurately reflect the risk of AOEs with ponatinib. The ongoing ponatinib dose-ranging OPTIC study will further evaluate dose-dependent AOE incidence rates. Keywords: acute lymphoblastic leukemia, adverse event, arterial occlusive event, chronic myeloid leukemia, CML, PACE, ponatinib, safety, tyrosine kinase inhibitor CML-104 E f fi cacy o f Generic Ima t inib Af t er Swi t ching fr o m O riginal in Trea t men t o f Pa t ien t s wi t h Chr o nic Myel o id Leukemia in t he Republic o f N o r t h Maced o nia - A Single - Cen t er E xperience Dushko Dukovski*, Sanja Trajkova, Simona Stojanovska, Nevenka Ridova, Irina Panovska- Stavridis Clinic for hematology, Skopje, Republic of North Macedonia Context: Imatinib, selective tyrosine kinase inhibitor (TKI), revolutionized treatment of chronic myeloid leukemia (CML) and changed the natural history of the disease. In 2013, a generic formulation came into the Republic of North Macedonia’s market and replaced the original formulation, Glivec. Objective: The aim of the study is to determine whether the efficacy of the generic Imatinib is the same as the original Imatinib-Glivec in patients treated for chronic myeloid leukemia in North Macedonia in terms of hematological and molecular responses in CML. Design: This is an observational retrospective study using medical charts of patients diagnosed with CML in the chronic phase who were previously successfully treated with original Imatinib and subsequently switched to generic Imatinib. The patients were treated with generic Imatinib from the year 2013 to 2020. Patients or other participants: 30 patients have been switched from original to generic Imatinib. All of them were receiving Imatinib at a dose of 400 mg/ daily prior and after switching. 17 (56.6%) of all patients were male, 13 (44%) were female. 28 of the patients completed the study, 2 of the patients lost their molecular response and were switched to second-generation TKI-Nilotinib. Results: 30 patients have been switched to generic imatinib. Before the switch, all of the patients were in complete hematologic response (CHR), and all of them were in MMR. Patients have received generic Imatinib for a median of 88 months. Molecular response (MR) was decided with BCR-ABL1 gene transcript ratio that is reported as International Scale (IS). Complete hematologic response was accepted as white blood cells < 10×10 9 /L, basophils <5%, no myelocytes, promyelocytes, myeloblasts in the differential, platelet count < 450×10 9 /L and non-palpable spleen. All of them maintained their hematologic response. Molecular responses after switching were stable in 83.3% (25), improved in 3.3% (1), and worsened in 13.3% (4). After switching, only 3.3% (1) reported anemia as a side effect and had not reported a new adverse event. Conclusions: In our observational series, most of the patients maintained their molecular response. The change from original to generic Imatinib appears to maintain efficacy and maintained CHR and MMR. Keywords: CML, imatinib, selective tyrosine kinase inhibitor (TKI), chronic myeloid leukemia CML-105 A Valida t i o n o f Vascular Adverse E ven t s Risk Assessmen t Me t h o d f o r J apanese CML Pa t ien t s wi t h Tyr o sine K inase Inhibi to rs Wataru Kamata*, Shku Sato, Shun Tsunoda, Satomi Okada, Yotaro Tamai Division of Hematology, Shonan Kamakura General Hospital, Kamakura, Japan Background and Aim: Tyrosine kinase inhibitors (TKIs) have substantially improved the prognosis of chronic myeloid leukemia (CML). However, TKIs can cause serious vascular adverse events (VAEs) such as ischemic heart disease (IHD), peripheral artery occlusive disease (PAOD), cerebral infarction (CI), and pulmonary embolism (PE). The Framingham general cardiovascular risk scores (FRS), Suita score (SS), and SCORE (Systematic Coronary Risk Evaluation) system are commonly used to predict the incidence of cardiovascular events, but their usefulness as evaluation methods for patients with CML is unknown. We aimed to determine the appropriateness of these evaluation methods for a Japanese CML cohort. Methods: We retrospectively surveyed patients with CML who visited our institute between January 2003 and March 2020. All patients were evaluated using the three risk assessment tools (FRS, SS, low-risk SCORE chart). To predict the 5-year event-free survival, we determined the cut-off values of each scoring system from the receiver operating characteristic analysis (ROC) curve. Results: Sixty-nine patients with CML (38 males) were registered. Their median age was 66 years (range, 25–91years), and the median follow-up time was 48 months. Eight patients (2 males) had VAEs (3 IHD, 2 PAOD, 1 CI, 1 PE, and 1 sudden death). Four patients were treated with nilotinib, 2 with imatinib,1 with dasatinib, and 1 with bosutinib. The cut-off values obtained from the ROC curve for the SS and SCORE chart were 45 and 2, respectively. The sensitivity,