S882 OPTIMIZATION OF TKI TREATMENT IN ELDERLY PATIENTS WITH PH+ CHRONIC MYELOID LEUKEMIA AND STABLE MR3.0 OR MR4.0: 1ST YEAR RESULTS OF THE ITALIAN MULTICENTRIC PHASE-III RANDOMIZED OPTKIMA STUDY
Authors: M. Malagola, F. Efficace, N. Polverelli, F. Cottone, E. Abruzzese, A. Iurlo, C. Bucelli, F. Stagno, M. Bonifacio, M. D’Adda, M. Lunghi, M. Crugnola, F. Lunghi, F. Castagnetti, G. Rosti, M.L. Ferrari, M. Bergamaschi, G. Binotto, R. Sancetta, M.R. Coppi, V. Giai, G. Rege Cambrin, A. Romano, M. Tiribelli, S. Russo, L. Aprile, A.P. Falcone, S. Rupoli, A. Russo Rossi, E. Usala, B. Martino, L. Gandolfi, S. Bernardi, C. Zanaglio, M. Farina, M. Baccarani, D. Russo
Journal: HemaSphere (2019)

Background: Family planning is important in patients (pts) with chronic myeloid leukemia (CML) who can have a near normal lifespan in tyrosine kinase inhibitors (TKI) era. Management of CML on conceptions and pregnancies is not defined as cases are rare and data are scarce. To investigate this issue a multicenter retrospective and prospective observational study of conception/pregnancy in CML pts was initiated within the European LeukemiaNet (ELN) from February 2014 till present. All ELN centers and participants from other countries were invited and received the study's protocol which was adopted in agreement with specific national laws. Aims: The main goal was to describe CML pts in terms of pregnancy/conceptions management and outcome. Secondary goals included demographics, characteristics of CML, management during pregnancy, pregnancy outcomes and characteristics of children. Methods: Adult pts aged ≥18 years with Ph+ positive CML and pregnancy were included after signing a written informed consent. Data were collected either in the coordinating centers in Moscow (Russia) and Rome (Italy) followed by the analyses of the entire data set. A total 305 pregnancy cases in 234 CML female pts from 15 centers of 13 countries worldwide were analyzed (Table 1). Results: Chronic phase at diagnosis was in 217/221(98%) pts. In 50 (21%) pts CML was diagnosed during pregnancy, while 184 (67%) got pregnant after diagnosis. Median (Me) time from CML diagnosis to pregnancy was 59 months (range 1–203). The outcomes of 305 pregnancies were as follows: labor 234 (77%), induced abortion 42 (14%), spontaneous abortion 21 (7%) and ongoing pregnancy or unknown outcome 8 (2%). Labor at full term was in 141 (75%) of 187 cases fully reported (Table 2). Molecular response (MR) evaluations at the start of pregnancy were recorded in 249/305 cases. Deep MR (DMR or BCR-ABL≤0,01% IS), major MR (MMR or BCR-ABL≤0,1%> >0,01% IS), MR2 (BCR-ABL>0,1%> ≤1% IS) and no MR2 (BCR-ABL>1% IS) was observed in 80 (32%), 31 (12%), 32 (13%) and 106 (43%) cases respectively. In 182 (71%) of 257 pregnancies with known data pts conceived while on TKI: 77% under imatinib (IM) and 23% TKI 2nd/3rd generation. TKIs were usually stopped early in 1st trimester (4–5 week of gestation) when the pregnancy was discovered. In 82 pregnancies pts were treated during 2nd-3rd trimester, after placental formation, until labor with IM: 33 (40%) of cases), nilotinib (NIL): 8 (9%), interferon (IFN): 23 (28%, 1 PEG-IFN), hydroxyurea: 6 (7%). IM was used throughout pregnancy in 13 (16%). One case of leukaferesis was recorded. The number of born children in 226 fully reported labors was 233 (including twins). Congenital abnormalities were recorded in 4 (1,7%) cases as follows: polydactyly (1), hypospadias (1) and non-closed foramen ovale of interatrial septum (2). None of the abnormalities were severe or life threatening, relationship to TKI use was considered unlikely by physicians. Low birth weight was recorded in 13 children with IM or NIL exposure at late pregnancy. The follow-up of all children was uneventful, with Me age at follow-up of 5 years (range 2 months-17 years).Summary/Conclusion: Most pregnancies in CML female pts resulted in normal childbirth with no increased rate of birth abnormalities in spite of TKI use at conception even if treatments were mostly early stopped at implant (4–5 weeks). Different therapies were used during pregnancy when needed. The results in terms of conception/pregnancy may be valuable for the development of CML treatment schemes particularly considering the variety of disease status.