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• Inflammatory myopathies (IM) are rarely associated to myelodysplastic syndromes (MDS). • Dermatomyositis and anti-TIF1g + are the most frequent forms of IM associated to MDS. • Antisynthetase syndrome is not observed in MDS patients. • Association with MDS has a negative impact on IM patients' survival. Patients with inflammatory myopathies (IM) are known to have an increased risk of developing malignancies. Autoimmune and inflammatory diseases occur in up to 25% of patients with myelodysplastic syndrome (MDS). This study aimed to describe the rare association between IM and MDS. We report here the main characteristics, treatment, and outcome of 21 patients (11 national cases and 10 additional cases from a literature review) with IM associated to MDS. Median age of patients at IM diagnosis was 66 years (range 26 – 78). Diagnosis of the two conditions were concomitant in most patients (n=14/21) whereas MDS diagnosis preceded IM diagnosis in 5 patients. Different types of IM were observed but dermatomyositis was the most frequent (59%). Compared to IM without MDS (IM/MDS−), patients with MDS (IM/MDS+) were older (median 66 vs 55, p=0.3), more frequently male (sex ratio M/F 1.125 vs 0.41, p=0.14) and positive for anti-TIF1γ (24% vs 4%, p=0.0039). Antisynthetase syndrome was never observed among IM/MDS+ patients (0% vs 28%, p=0.01). MDS WHO type was not univocal, but the prognostic score was of low risk in almost all cases. IM was usually steroid sensitive (82% of patients) but often steroid dependent (56% of patients). Overall survival of IM patients with MDS was worse compared to patients with IM without MDS (p=0.0002). IM associated with MDS are mainly represented by dermatomyositis and/or anti-TIF1γ autoantibodies. Antisynthetase syndrome has not been described in association with MDS. Despite low-risk MDS, overall survival of IM patients with MDS is worse than IM patients without MDS. [ABSTRACT FROM AUTHOR]

Objectives: To assess the reduction of transfusions rate in transfusion-dependent patients with low-risk myelodysplastic syndrome (MDS) with iron overload treated with deferasirox. Methods: Prospective observational study. Primary endpoint was reduction in transfusion requirements (RTR) at 3 months, (assessed on 8-week period). Secondary end-points were hematologic improvement according to International Working Group (IWG) 2006 criteria at 3, 6, and 12 months. Results: Fifty-seven patients were evaluable. After 3 months of chelation, no effect was seen on transfusion requirement (5.9 packed red blood cells (PRBC) vs 5.8 before chelation). According to the Kaplan-Meier analysis, the probability of RTR at 3, 6, and 12 months was assessed as 3.5%, 9.1%, and 18.7%, respectively. Median duration of RTR was 182 days. However, during the 12-month follow-up after deferasirox initiation, 17 patients (31.5%) achieved minor erythroid response [HI-E] according to IWG criteria, 10 of whom having achieved Hb improvement at month 12. Conclusion: After 3 months of treatment, deferasirox had no impact on transfusion requirement in regularly transfused patients with low-risk MDS. However, deferasirox could induce 31% of erythroid response during the 12-month follow-up period thus suggesting that iron chelation therapy with deferasirox may induce an effect on hematopoiesis in a subset of patients with MDS and iron overload. [ABSTRACT FROM AUTHOR]

Background Systemic inflammatory and autoimmune diseases (SIADs) associated with myelodysplastic syndromes are often difficult to treat. Corticosteroids are efficient but only usually at high doses. The use of biologics needs to be specified. Methods In a French multicenter retrospective study, we analyzed the efficacy and safety of biologics (tumor necrosis factor-α [TNF-α] antagonists, tocilizumab, rituximab and anakinra) for SIADs associated with myelodysplastic syndromes (MDSs). Clinical, biological and overall treatment responses were evaluated. When several lines of treatment were used, data were analyzed before and at the end of each treatment line and were pooled to compare overall response among steroids, disease-modifying anti-rheumatic drugs (DMARDs) and biologics. Results We included 29 patients (median age 67 years [interquartile range 62–76], 83% males) with MDS-related SIADs treated with at least one biologic. The MDSs were predominantly refractory anemia with excess blasts 1 (38%) and refractory cytopenia with multilineage dysplasia (21%). The SIADs were mainly arthritis ( n = 6; 20%), relapsing polychondritis ( n = 8; 30%) and vasculitis ( n = 10; 34%). During a 3-year median follow-up (IQR 1.3–4.5), a total of 114 lines of treatments were used for all patients: steroids alone (22%), DMARDs (23%), TNF-α antagonists (14%), anakinra (10%), rituximab (10%), tocilizumab (7%) and azacytidine (9%). Considering all 114 lines, overall response (complete and partial) was shown in 54% cases. Overall response was more frequent with steroids (78%) and rituximab (66%) than DMARDs (45%) and other biologics (33%) ( p < 0.05). Rituximab had better response in vasculitis and TNF-α antagonists in arthritis. During follow-up, 20 patients (71%) presented at least one severe infection. Conclusion This nationwide study demonstrates the efficacy of steroids for SIAD-associated MDSs but a high frequency of steroid dependence. The response to biologics seems low, but rituximab and azacytidine seem promising. [ABSTRACT FROM AUTHOR]

Survival after azacitidine (AZA) failure in higher-risk myelodysplastic syndromes (MDS) is poor and new treatment options are needed. Erlotinib, an oral inhibitor of the epidermal-growth-factor-receptor (EGFR), has shown in preclinical models some efficacy in higher risk MDS and acute myeloid leukemia (AML). In this phase I/II trial, 30 patients received 100 mg/day ( n = 5) or 150 mg/day ( n = 25) of Erlotinib orally after primary or secondary resistance to AZA treatment. Eighteen MDS and 12 AML patients were treated. This outpatient treatment was well tolerated with limited grade III–IV extra hematological toxicities (skin ( n = 1), and diarrhea ( n = 3). Response was observed in 6 patients (20%) including 1 complete remission (CR), 1 marrow CR and 4 hematological improvement (2 erythroid and 2 on platelets). Median duration of response was 5 months. Erlotinib appears to induce a significant number of responses in higher risk MDS/AML having failed AZA treatment. Given the good safety profile of Erlotinib, its combination with other drugs could be tested in the future in MDS and AML. [ABSTRACT FROM AUTHOR]

Abstract: ESAs are increasingly used to treat anemia of lower risk MDS, even before RBC transfusion requirement. From a previously published patient cohort treated with ESAs, we selected 112 patients with de novo low or int-1 IPSS MDS with Hb<10g/dl, serum EPO<500UI/l and who had never been transfused. Erythroid response rate at 12 weeks was 63.1% (IWG 2006). In multivariate analysis, an interval between diagnosis and ESA onset<6 months, Hb level>9g/dl, and serum EPO<100UI/l predicted better response to ESA while shorter interval between diagnosis and ESA onset (p =0.01), lower serum EPO (p =0.04) and WHO diagnosis of RCMD-RS (p =0.03) were associated with longer response. Median interval from diagnosis to transfusion dependency was 80 months and 35 months, respectively, in patients with onset of ESA <6 months and ≥6 months from diagnosis (p =0.007). Those results support early onset of ESA in lower risk MDS, to better avoid the consequences of anemia. Early introduction of ESA may also delay the need for RBC transfusions, hypothetically by slowing the disease course, but prospective studies are required to further assess this point. [ABSTRACT FROM AUTHOR]

Abstract: Background: Iron chelation therapy (CT) improves survival in thalassemia major but its beneficial effects on survival in MDS patients remain uncertain. Methods: We analyzed, by multivariate analysis, survival and causes of deaths in 97 low or intermediate 1 IPSS patients regularly transfused as outpatients, chelated or not, who were included during a month period and followed for 2.5 years. Results: 44 (45%) of patients were not chelated and 53 (55%) received CT, mainly with deferoxamine, for at least 6 months (median duration of chelation 36 months, range 6–131+). During the follow-up period, 66 of the 97 patients died, including 51% and 73% of chelated and non-chelated patients, respectively. Median overall survival was 53 months and 124 months in non-chelated and in chelated patients (p <0.0003). Causes of death did not significantly differ between the two groups (p =0.51). In multivariate Cox analysis, adequate chelation was the strongest independent factor associated with better OS. Conclusion: Iron chelation therapy appears to improve survival in heavily transfused lower risk MDS, but prospective randomized studies are required to confirm our findings, and to determine more precisely the mechanisms of this potential survival benefit. [Copyright &y& Elsevier]