Different Repo Doses (High vs Standard) for Treatment of Anemia in MDS Patients: A Survey from the Italian MDS Registry

Poster Presentations – 14th International Symposium on Myelodysplastic Syndromes / Leukemia Research 55 S1 (2017) S45–S167

acquired two or more additional aberrations and developed complex karyotypes (≥3 changes). Their median survival from the emergence of CCE was 7 months (range 1–30 months). In 17/25 patients (68%), CCE was associated with mutations of TP53 and/or unbalanced aberrations of 17p. Changes acquired during CCE involved most frequently unbalanced aberrations of the chromosomes: 1 (8×), 7 (8×), 8 (8×), 12 (10×) and 17 (11×). In six patients, deleted 5q was involved in complex rearrangements. CCE was detected in 13.6% patients with MDS and isolated del(5q). This finding was strongly associated with higher frequency of TP53 gene alterations (deletions, aUPD, mutations), short survival, disease progression and/or transformation to AML. Inactivation of TP53 gene may be a critical early event during CCE of 5q- clones, triggering genetic instability and acquisition of secondary aberrations. Our results substantiate a need for regular molecularcytogenetic monitoring of MDS patients with isolated del(5q) to help with treatment decision. Acknowledgement: Supported by RVO-VFN64165, GACR P302/12/ G157, ProgresQ28, MHCR 00023736.

91 DIFFERENT REPO DOSES (HIGH VS STANDARD) FOR TREATMENT OF ANEMIA IN MDS PATIENTS: A SURVEY FROM THE ITALIAN MDS REGISTRY E. Balleari1, C. Salvetti2, R. Filiberti3, B. Allione2, E. Angelucci4, M. Cavalieri5, M. Cavalleri6, D. Cilloni7, M. Clavio4, E. Crisa’2, A. Da Col1, P. Danise8, A. Di Tucci9, C. Finelli10, R. Lemoli4, M. Miglino4, E. Oliva11, M. Pellegrino12, A. Poloni13, V. Santini14 1 Internal Medicine, IRCCS-AOU San Martino-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; 2AOU città della salute, hematology – University of Turin, Turin, Italy; 3Epidemiology, IRCCS-AOU San Martino-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; 4 Hematology-Oncology, IRCCS-AOU San Martino-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; 5Medicine, UO Internal Medicine, Savona, Italy; 6Medicine, UO Internal Medicine, Sestri Levante, Italy; 7AOU Città della Salute, Internal Medicine – University of Turin, Turin, Italy; 8Hematology, Nocera Hospital, Nocera Inferiore, Italy; 9Hematology, AOU Cagliari, Cagliari, Italy; 10Istituto Seragnoli, Hematology- Bologna University, Bologna, Italy; 11Hematology, Ospedali Riuniti, Reggio Calabria, Italy; 12Hematology, IRCCS CROB, Rionero sul Vulture, Italy; 13UO Hematology, Hematology-University delle Marche, Ancona, Italy; 14Hematology, AOU Careggi, Florence, Italy Introduction: REPO has been used to treat anemia in MDS anemic pts since more than 25 years. In early Ninety this treatment, using different but usually “standard” doses (inferior or equal to 30– 40.000 IU weekly), showed a disappointing overall response-rate of 15–25%. In recent years most studies reported a response rate of more than 50%, either because of a better selection of patients of MDS and possibly because higher doses (60–80.000 UI weekly) of rEPO is increasingly used. Nevertheless, a direct comparison between the two different schedules of rEPO treatment is still lacking. Methods: Within the framework of the Italian Network of regional MDS registries of FISM a cohort of 106 anemic MDS pts treated with higher doses of rEPO (40.000 IU twice a week, H) for at least 3 months were identified; a second cohort of 212 pts similar for clinical parameters known to influence response to rEPO and treated with standard doses (40.000 IU weekly, S) were compared in a 1:2 fashion. Univariate and multivariate analysis were performed as appropriate in order to identify factors influencing clinical response. Results: Characteristics of subjects were: median Hb pre-treatment 8.9 g/dL in H cohort and 9.1 g/dL in S cohort, IPSS score Intermediate-2/high in 5% of H cohort and 8% of S cohort,

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transfusion-dependency in 25% of H cohort and 26% of S cohort, median EPO 79 IU in H cohort and 69 IU in S cohort. After 3 months of rEPO treatment, the overall erythroid response-rate (IWG 2006 criteria) in the two cohorts was 53% (163 out of 309 pts). No difference in erythroid response-rate was found between MDS pts in H cohort when compared to pts in S cohort (48% responders in the H cohort vs 55% responders in the S cohort ( p = 0.23). IPSS score, transfusion-dependency and EPO serum levels at diagnosis were statistically associated with response in both cohorts. At multivariate analysis, significantly lower response-rates to rEPO were related with transfusion-dependency (yes vs no, OR = 0.59 (95%CI: 0.44–0.79, p < 0.001), higher endogenous serum EPO levels at diagnosis (>500 vs <=500, OR = 0.36 (95%CI: 0.19–0.68, p = 0.002) and higher IPSS score (intermediate 2/ high vs, intermediate 1/ low, OR = 0.42 (95%CI: 0.24–0.74, p = 0.003). Conclusions: Our data, although derived by a retrospective analysis, indicate that standard doses of rEPO are at least as effective as higher-doses for correcting anemia in lower-risk MDS patients. Prospective, randomized studies addressing this point are necessary.

92 MANAGEMENT OF MYELODYSPLASTIC SYNDROMES WITH ERYTHROPOIESIS STIMULATING AGENTS (ESAS) IN REAL-LIFE EXPERIENCE: AN UPDATE FROM RECAMDS C. Cerchione1, O. Vitagliano1, R. Della Pepa1, G. Cerciello1, A.E. Pareto1, M. Di Perna1, I. Soriente1, A.M. D’Arco2, P. Danise2, F. Alfinito1, F. Pane1 1 Hematology, AOU Federico II, Napoli, Italy; 2Hematology, Ospedale Pagani, Pagani SA, Italy Erythropoiesis stimulating agents (ESAs) are the frontline treatment in low-risk anemic MDS patients and an employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. It’s matter of debate whether the clinical response is a result of proliferation and maturation of the dysplastic clone or stimulation of residual normal erythropoiesis by ESAs. Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS: an analysis of the erythropoietic response to ESAs therapy in a cohort of anemic non trasfusion-dependent MDS patients, enrolled in a retrospective register, RECAMDS, subgroup of Italian register, was performed. 183 patients, treated with standard-dose ESAs, have been retrospectively analyzed (Table 1). Data analysis was performed, according to IWG 2006 criteria, at the baseline, after 3 and 6 months of continuous treatment, with a subanalysis of the patients according to WHO and R-IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dL, mean serum EPO concentration: 51 mU/L, after a mean time from diagnosis of 6 months (r.1–118). Overall response rate (ORR) was 83.6% (153/183), no difference among WHO and IPSS subgroups was found: 132/183 (72.1%) achieved response after 3 months of treatment, while other 21/183 (11.2%) after 6 months. 19 patients with stable disease (nonresponders, according to IWG criteria), in which treatment was continued, achieved response after 9 months. In the macrocyticresponders group 83.2% exhibits again macrocytosis after 3 months, while 16.8% become normocytic. In the normocyticresponders group 89.8% exhibits again normocytosis, while 10.2% become macrocytic: in these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia, with transfusion-dependence, regarded as first signs of progression of disease. Non-responders were 30/183 (16.3%): in the macrocytic