Outcome of Lower-Risk Patients with Myelodysplastic Syndromes without 5Q Deletion after Failure of Erythropoiesis Stimulating Agents

Oral Presentations – 14th International Symposium on Myelodysplastic Syndromes / Leukemia Research 55 S1 (2017) S8–S36

while–7, del(5q), del(20q), +8, del(7q), –Y, t(11q23;varia), and del (11q) were found also as single anomalies. Aberrations as del(4q), del(3p), and der(1;7) were more often found after haematological malignancies, while –17, del(17p) and der(17p) were predominantly preceded by solid tumours. Trisomies occurred preferentially after chemotherapy only, while –Y was relatively frequent after radiotherapy. Translocations as der (1;7), t(3q26;varia), t(3q21;varia), and t(11q23;varia), as well as monosomies, mainly occurred after radiochemotherapy. After alkylating agents, patients were more prone to present with additions, chromosome 12 abnormalities, the 3 recurrent translocations, del(9q), and der(1;7). In patients who did not receive alkylating agents, −Y, +22, and del(4q) were the most frequent. Most of 17p abnormalities were found after topoisomerase II inhibitor-free regimens, while translocations were often associated with this treatment, as known for t-AML. A short latency period <=3 years was often seen in patients with balanced translocations, while several monosomies (−6, −10, −22, −Y), add(7q), del(6q), inv (3q), and 17p abnormalities used to appear after very long latency periods (>=12 years). Regarding prognosis, isolated del(5q) retains good prognostic impact, that drastically worsens with only one additional abnormality, in sharp contrast to primary disease; del(20q) as single or double change behaves similarly; del(7q) as single or double anomaly has the same poor prognosis as −7, again in contrast to primary disease. t(11q23;varia) is mostly found isolated, with an extremely poor prognosis. In conclusion, the categorization of chromosomal abnormalities in meaningful biological categories has enabled us to carry out a thorough description of the cytogenetic findings in this large series of t-MDS, that may help to understand mechanisms involved in disease evolution. Important differences between primary and t-MDS concerning prognostication have become evident in this preliminary analysis, which justify the establishment of a distinct t-MDS prognostic scoring system. 49 OUTCOME OF LOWER-RISK PATIENTS WITH MYELODYSPLASTIC SYNDROMES WITHOUT 5Q DELETION AFTER FAILURE OF ERYTHROPOIESIS STIMULATING AGENTS S. Park1, J.F. Hamel2, A. Toma3, C. Kelaidi4, S. Thepot5, M. Campelo Diez6, V. Santini7, M. Sekeres8, E. Balleari9, J. Kaivers10, K. Goetze11, O. Beyne-Rauzy12, A. Stamatoullas13, I. Kotsianidis14, R. Komrokji15, D. Steensma16, U. Germing10, G. Sanz17, F. Dreyfus18, P. Fenaux19 1 CHU Grenoble, Hematology, Grenoble, France; 2CHU d’Angers, Departement de statistiques, Angers, France; 3CHU Henri MondorAPHP, Hematology, Paris, France; 4CHU Avicenne, Hematology, Avicenne, France; 5CHU Angers, Hematology, Angers, France; 6Hospital Universitario de Salamanca, Hematology, Salamanca, Spain; 7 University of Florence, Hematology, Florence, Italy; 8Cleveland Clinic Taussig Cancer Institute, Leukemia Program, Cleveland, USA; 9IRCCS Azienda Ospedaliera Universitaria San Martino di Genova, Dipartimento di Terapie Oncologiche Integrate, Genova, Italy; 10 University Dusseldorf, Hematology, Dusseldorf, Germany; 11 Klinikum rechts der Isar Technische Universität München, Hematology, Munchen, Germany; 12IUCT Oncopole, Medicine, Toulouse, France; 13Centre Henri Becquerel, Hematology, Rouen, France; 14University Hospital of Alexandroupolis, Hematology, Alexandroupolis, Greece; 15H. Lee Moffitt Cancer Center and Research, Hematology, Tampa, USA; 16Dana-Farber Cancer Institute, Hematology, Boston, USA; 17Hospital Universitario y Politecnico La Fe, Clinical Hematology & Hematopoietic Cell Transplantation Unit, Valencia, Spain; 18Hopital Cochin- APHP, Hematology, Paris, France; 19 CHU Saint Louis- APHP, Hematology, Paris, France

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Purpose: Most anemic non-del (5q) lower-risk myelodysplastic syndromes (MDS) patients are treated with erythropoiesis stimulating agents (ESAs), with a response rate of approximately 50%. Second line treatments (TX), including hypomethylating agents (HMA), lenalidomide (LEN) and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure, and the effect of second line TX. Methods: International retrospective cohort of 1,698 non-del5q lower-risk MDS patients treated with ESAs. Results: Erythroid response (HI-E) to ESAs was 61.5%, and median response duration was 17 months. Of 1,147 patients with ESA failure, 653 had primary failure and 494 relapsed after a response. Primary failure to ESA was associated with a higher risk of AML progression, which did not translate into an OS difference. The 5year cumulative incidence of AML transformation in patients with primary or secondary failure was 16.7% and 8.1% respectively ( p = 0.0001). With a median follow-up of 41 months, the median survival from ESA failure was 52.2 and 60.4 months for primary refractory patients and relapsing patients, respectively ( p = 0.12). Of 450 (39%) patients who received a second-line treatment (TX2), 194 received HMAs, 148 LEN and 108 other treatments (MISC), while 697 received RBC transfusions only. The 5-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for HMA, LEN and MISC, respectively ( p = 0.05). 5-year OS for patients receiving HMA, LEN or MISC was 36.5%, 41.7% and 51% respectively (p = 0.21). In a multivariate analysis adjusted for age, gender, IPSS-R, and progression at ESA failure, there was no significant OS difference among the 3 groups. Age > 75y (HR 1.73, p < 0.001), intermediate IPSS-R (HR 2.86, p < 0.001) remained significantly associated with a worse OS. There was no significant influence of treatment as a time-dependent variable on OS (HR 1.26 for HMA, p = 0.08, and HR 1.13 for LEN, p = 0.51). Conclusion: In this large, multicenter, retrospective cohort of nondel 5q lower-risk MDS pts treated with ESAs, none of the most commonly used second-line treatments (HMA and LEN) significantly improved OS. Early failure to ESA was associated with a higher risk of AML progression. This study may be important in designing future clinical trials in lower-risk MDS patients failing ESAs, in whom novel treatments are required. Parameters predicting a worse outcome, including IPSS-R subtype and the duration of response to ESA, could indicate a more intensive therapeutic approach, including allogeneic stem cell transplantation.

50 ADDING MOLECULAR DATA TO PROGNOSTIC MODELS CAN IMPROVE THEIR PREDICTIVE POWER IN TREATED PATIENTS WITH MYELODYSPLASTIC SYNDROMES (MDS) A. Nazha1, K. Al-Issa1, A. Zarzour1, T. Radivoyevitch2, B. Hamilton1, A. Gerds1, S. Mukherjee1, V. Adema2, M. Clemente2, B. Patel2, C. Hirsch2, A. Advani2, P. Bartlomiej2, H. Carraway1, J. Maciejewski2, M. Sekeres1 1 Cleveland Clinic- Taussig Cancer Institute, Hematology and Medical Oncology, Cleveland, USA; 2Translational Hematology and Oncology Research Department, Cleveland Clinic- Taussig Cancer Institute, Cleveland, USA Background: Several prognostic scoring systems (SS) have been developed to risk stratify patients ( pts) with MDS including: the International Prognostic Scoring System (IPSS), Revised IPSS (IPSSR), World Health Organization classification-based Prognostic Scoring System (WPSS), and MD Anderson Prognostic Scoring System (MDPSS). Incorporation of molecular data into the IPSS-R can improve its predictive power. In this study, we evaluated the impact of adding molecular data to established models in MDS.