Search

Korrektur zu 10.1038/s41375-020-0826-9

Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800 mg ('high-dose') imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-escalation of the dose intensity under high-dose imatinib can be safely performed without increasing the risk of losing deep molecular response is unknown. To gain insights into this clinically relevant question, we analyzed the outcome of imatinib dose reductions from 800 mg to 400 mg daily in the Chronic Myeloid Leukemia-Study IV. Of the 422 patients that were randomized to the 800 mg arm, 68 reduced imatinib to 400 mg after they had achieved at least a stable major molecular response. Of these 68 patients, 61 (90%) maintained major molecular remission on imatinib at 400 mg. Five of the seven patients who lost major molecular remission on the imatinib standard dose regained major molecular remission while still on 400 mg imatinib. Only two of 68 patients had to switch to more potent kinase inhibition to regain major molecular remission. Importantly, the lengths of the intervals between imatinib high-dose treatment before and after achieving major molecular remission were associated with the probabilities of maintaining major molecular remission with the standard dose of imatinib. Taken together, the data support the view that a deep molecular remission achieved with high-dose imatinib can be safely maintained with standard dose in most patients. Study protocol registered at clinicaltrials.gov 00055874.

Leukemia : normal and malignant hemopoiesis 30(6), 1255-1262 (2016). doi:10.1038/leu.2016.20, Published by Nature Publ. Group, Basingstoke

Internal tandem duplications (ITDs) of the juxtamembrane region of the FLT3 tyrosine kinase receptor are the most frequent genetic alterations in acute myeloid leukemia (AML). The presence of this mutation has been recognized as an independent poor prognostic factor. In this study, we compared the FLT3 mutational status between diagnosis and subsequent relapses in 31 patients with AML. At diagnosis, seven patients were identified to contain FLT3-ITD mutations and one patient to harbor the D835 mutation. Five patients remained FLT3-ITD positive throughout the disease course (+/+). Three patients lost the FLT3 gene mutation at first (one FLT3-ITD, one D835 mutation), or second relapse (one FLT3-ITD) (+/-). One additional patient lost a small FLT3-ITD positive clone at relapse and at the same time gained an apparently unrelated FLT3-ITD positive clone. One patient without FLT3 mutation at diagnosis relapsed with an FLT3-ITD mutation (-/+). A shorter median duration of first remission (6 months versus 11.5 months) and a higher relapse rate after salvage therapy (e.g. allogeneic peripheral blood stem cell transplantation) resulted in a lower leukemia-free survival in the FLT3 mutated group (11% versus 31%). The loss of a clone with a mutation in the FLT3 gene at relapse did not improve the prognosis.

Background Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400mg/day (n=400) could be optimized by doubling the dose (n=420), adding IFN (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). Methods From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. The impact of patients' and disease factors on survival was prospectively analyzed. At the time of evaluation, at least 62% of patients still received imatinib, 26.2% were switched to 2nd generation tyrosine kinase inhibitors. Results After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival 80% and 10-year relative survival 92%. In spite of a faster response with IM800mg, the survival difference between IM400mg and IM800mg was only 3% at 5 years. In a multivariate analysis, the influence on survival of risk-group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs. other) was significant in contrast to any form of initial treatment optimization. Patients that reached the response milestones 3, 6 and 12 months, had a significant survival advantage of about 6% after 10 years regardless of therapy. The progression probability to blast crisis was 5.8%. Blast crisis was proceeded by high-risk additional chromosomal aberrations. Conclusions For responders, monotherapy with IM400mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease and blast crisis, more life-time can currently be gained by carefully addressing non-CML determinants of survival. Disclosures Hehlmann: Novartis: Research Funding; BMS: Consultancy. Saussele: Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Pfirrmann: BMS: Honoraria; Novartis: Honoraria. Krause: Novartis: Honoraria. Baerlocher: Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria. Bruemmendorf: Novartis: Research Funding. Müller: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Ariad: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Jeromin: MLL Munich Leukemia Laboratory: Employment. Hänel: Roche: Honoraria; Novartis: Honoraria. Burchert: BMS: Honoraria. Waller: Mylan: Consultancy, Honoraria. Mayer: Eisai: Research Funding; Novartis: Research Funding. Link: Novartis: Honoraria. Scheid: Novartis: Honoraria. Schafhausen: Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Ariad: Honoraria. Hochhaus: Incyte: Research Funding; MSD: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; BMS: Research Funding; ARIAD: Research Funding.

Platelet production is primarily regulated by the thrombopoietic cytokine thrombopoietin (TPO). In most cases thrombopoietin serum levels are determined by the rate of c-mpl receptor-mediated degradation after TPO uptake into platelets and megakaryocytes. The contribution of increased TPO protein synthesis by a translational mechanism was recently appreciated as the cause for hereditary thrombocythemia and will have to be elucidated in other conditions of thrombocytosis in association with increased TPO levels.

An inherent defect of erythroid differentiation at the colony-forming unit blast (CFU-blast) compartment and (or) an impaired response of early erythroid progenitors (BFU-E) to growth stimulation are both considered to contribute to anemia in myelodysplastic syndromes (MDS). With the intention of improving survival and growth of early erythroid progenitors we investigated the effect of stem-cell factor (SCF) and interleukin-3 (IL-3) alone and in combination with erythropoietin, on the in vitro erythropoiesis of 13 patients with MDS and of three normal controls. SCF and IL-3 alone did not promote erythroid colony growth in MDS, while 3 cases responded to erythropoietin alone. In each of these, BFU-E colony growth could be increased by SCF, which was also found in all normal bone marrows. Altogether 6 cases showed a significant enhancement of BFU-E colony numbers by the combination of SCF and erythropoietin as compared to erythropoietin alone (P = 0.036). Out of the 6 responding cases, 5 belonged to the FAB-classified subgroups refractory anemia (RA) and refractory anemia with ringed sideroblasts (RA/RS) (5/5), while 1 patient was classified as having refractory anemia with excess of blasts (RAEB) (1/4). No patient with refractory anemia with excess of blasts in transformation (RAEB-T) (0/4) responded. In spite of these positive effects, the absolute number of BFU-E colonies remained reduced in all MDS cases when compared to normal controls. IL-3 proved ineffective in increasing the response to erythropoietin in MDS although it increased erythropoietin-induced BFU-E formation in normal controls significantly. We conclude that the striking synergistic effect of SCF and erythropoietin on erythroid colony formation seen with normal bone marrow is conserved in most cases with RA and RA/RS. In RAEB and RAEB-T the intrinsic defect of the erythroid differentiation pathway cannot be overcome by SCF.

Immunosuppression has recently been proposed for low-risk myelodysplastic syndromes (MDS) to reverse bone marrow failure by inhibiting intramedullary secretion of proapoptotic cytokines. We treated 35 MDS patients (24 refractory anaemia (RA), 10 RA with excess blasts and one chronic myelomonocytic leukaemia) with either horse antithymocyte globulin 15 mg/kg/day or rabbit antithymocyte globulin 3.75 mg/kg/day, each for 5 days. Median age was 63 years (range: 41-75). After 1 to 34+ months of follow-up (mean: 15+), four patients experienced complete haematological responses (CR), six good responses (GR) and two minor responses. All CRs and GRs occurred in patients with RA, in whom both horse and rabbit ATG yielded five responses out of 12 (42%). Time to response varied between 1 and 10 (mean: 3) months. The median duration of response was 9+ (1-17+) months; five patients are in continuing response. In all, 23 patients suffered side effectsdegrees II WHO (the degree of toxicity encountered according to the internationally accepted WHO toxicity grading); one patient died 2 weeks after rabbit ATG from rhinocerebral mucormycosis. Parameters that correlated with response were duration of disease and RA subgroup. In our experience, immune-modulating therapy with either horse or rabbit ATG is feasible in patients with RA and short duration of disease.

A prospective, randomized, double-blind placebo-controlled trial was designed to evaluate the impact of granulocyte/macrophage-colony-stimulating factor (GM-CSF) on the efficacy of sequential high-dose cytosine arabinoside/mitoxantrone chemotherapy (S-HAM) in adult patients with high-risk myelodysplastic syndromes (MDS). GM-CSF or placebo was given subcutaneously once daily at a dose of 250 microg/m2, starting 48 h prior to chemotherapy, and continued until neutrophil recovery. Owing to high toxicity and slow patient recruitement the study was closed and unblinded after 31 patients had been enrolled; 15 were randomized to receive placebo and 16 to receive GM-CSF. A total of 29 patients were evaluable for response; their median age was 57 years. Ten patients achieved a complete remission (34.5%), 9 patients had persistent MDS (31%), 10 patients died within 6 weeks after the onset of treatment (early death) (34.5%). The median remission duration was 190 days (range: 2.5-45 months). Among the 29 evaluable patients no significant differences could be found between the two study arms regarding complete remission rate [GM-CSF: 31% (5/16) versus placebo: 38% (5/13) P = 0.45], rate of persistent MDS [GM-CSF: 25% (4/16) versus 38% (5/13) P = 0.35), early death rate [44% (7/16) versus 23% (3/13) P = 0.22] and remission duration (GM-CSF: 87 days versus placebo 221 days). Duration of granulocytopenia (median: 33 days with GM-CSF) versus 35 days with placebo) and frequency of infectious episodes were not significantly influenced by GM-CSF. The small number of patients finally analyzed means that no definite conclusions about the effect of GM-CSF can be reached.

Therapy for myelodysplastic syndromes (MDS) has been less than effective when based on low-dose treatment or supportive measures only, including hematopoietic growth factors. Recently, based on the percentage of bone marrow blasts, the number of cytopenic cell lines and cytogenetics, clinical risk groups have been defined more precisely. Recent studies applying intensive acute myeloid leukemia (AML)-type therapy to high-risk MDS have produced remissions ranging from 45 to 79%. Advances in the understanding of the biology of MDS clearly point to cytogenetics rather than morphologic subtype as being of prognostic relevance. Hence, new treatments need to be developed for patients with unfavorable karyotypes and complex abnormalities in particular. These MDS subtypes are characterized by low spontaneous proliferative activity and low autocrine production of hematopoietic growth factors. The subtypes are, however, highly sensitive to external stimulation by granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF). New therapies could emerge from these findings, for example, priming high-risk MDS patients with hematopoietic growth factors in combination with intensive AML-type treatment. Recent studies suggest that incorporating high-dose AraC into an intensive drug combination could further improve the outcome of high-risk MDS.

We report on a patient with Fanconi's anemia (FA) who developed a myelodysplastic syndrome (RAEB-T) with complex karyotypic abnormalities (trp 1q23q42, monosomy 20, trisomy 13) at the age of 28. The patient achieved a complete hematological and cytogenetic remission after treatment with sequential high-dose cytosine arabinoside/mitoxantrone followed by G-CSF (5 micrograms/kg). Bone marrow hypoplasia was prolonged with 38 days of granulocytopenia500/microliters and 62 days of platelet transfusion dependency. Nonhematological toxicity did not exceed that of patients without underlying FA. Remission duration was 7 months. This observation shows the feasibility of high-dose Ara C treatment in patients with FA and MDS. Although hematopoiesis remained clonal in remission, the suppression of the cytogenetically abnormal clones transiently reversed the antecedent long-lasting pancytopenia.

Thirty-one adult patients with high-risk myelodysplastic syndromes (MDS) were enrolled in a prospective randomized double-blind placebo-controlled trial evaluating the efficacy of sequential high-dose Ara C/mitoxantrone chemotherapy with or without GM-CSF. GM-CSF or placebo was given subcutaneously once daily at a dose of 250 micrograms/m2 starting 48 h prior to chemotherapy and continued until neutrophil recovery. This design allowed us to investigate the role of GM-CSF as a priming factor for the leukemic clone, as well as its effect on the recovery of normal hematopoiesis. Twenty-eight patients are currently evaluable for response. The patients reached a complete remission (36%), eight patients had persistent MDS (29%), and ten patients died within 6 weeks after the onset of treatment (early death). Infectious complications during cytopenia were the major cause of death (8/10). Median time to complete hematologic recovery (neutrophils500/microliter and platelets 20,000/microliter) and time to neutrophil recovery above 1500/microliter was 29 and 35 days, respectively. Median remission duration was 190 days (6.4 months). Analysis of prognostic subgroups showed a low CR rate (25%) and a high early-death rate (44%) in patients55 years of age, suggesting that the intensified treatment approach should be limited to younger patients. No data concerning the influence of GM-CSF on response to chemotherapy or duration of neutropenia are presently available.

Patients with high-risk myelodysplastic syndromes (MDS) face a poor prognosis with a median survival time of less than 12 months. The only curvative treatment known so far is allogeneic bone marrow transplantation which is available for younger patients with an HLA-matched sibling and hence for a minority of cases only. Acute myeloid leukemia (AML)-type combination chemotherapy can achieve complete remissions (CR) in the range of 15%–51%, however, remission duration is short (1, 2). Treatment failures are due to primary drug resistance and a high early death rate. The latter may be related to a longer duration of treatment-induced aplasia as compared to AML.

Background Pomalidomide (POM) in a 1-arm phase-1/-2 study and a randomized 4-arm phase-2 study in MPN-associated myelofibrosis improved anemia. Pomalidomide was evaluated at doses of 0.5 and 2.0 mg/d. Aims To evaluate efficacy of POM alone at two different doses and combined with prednisolone (PRED) in patients with MPN-associated myelofibrosis and cytopenia (ClinicalTrials.gov No. NCT00949364). Methods Main inclusion criteria were RBC-transfusion-dependence or hemoglobin Results 38 patients were treated in cohort-1 and 58 in cohort-2 (N=27, PRED-mo-4; N=31; PRED-mo-7). Median follow-up was 30 mo in cohort-1 and 10 mo in cohort-2. Median age was 72 y (range, 49-85 y). 34% were female, 72% had primary MF. Disease-stage at study-entry (DIPSS) was high-risk, 24%, intermediate-2 risk, 65% and intermediate-1 risk 12%; JAK2V617Fand MPLW515L were detected in 58% and 6% of patients; 76% of patients were RBC- and 17% platelet-transfusion-dependent. There were no significant differences in pretreatment characteristics between cohort-1 and cohort-2 or between the 2 arms of cohort-2. Median durations of POM treatment were 12, 8, and 4 mo, respectively. PRED was added in cohort-1 and in the PRED-month-4 as well as PRED-month-7 arms of cohort-2 in 50%, 59% and 26% of patients. Response-rates were: 34% (95%-CI, 21-50%), 19% (95%-CI, 8-37%) and 16% (95%-CI, 7-33%), respectively; p=0.086. Responses occurred after 6 mo (range, 1-15 mo), 7 mo (range, 1-12 mo) and 4 mo (range, 3-7 mo). Anemia responses were observed more frequently in cohort-1 (29% [95%-CI, 17-45%]) compared to cohort-2 (14% [95%-CI, 7-25%]; p=0.059). Platelet response in patients with platelets100/nL were achieved in 56% (95%-CI, 27-81%) and 25% (95%-CI, 9-53%; p=0.20). 13 patients (12 high risk) experienced blastic transformation; 4 patients developed solid neoplasms. Conclusions Response rate to POM at a dose of 2mg/d was higher compared to 0.5 mg/d. Early addition of PRED at 4 mo compared to 7 mo was associated with longer treatment duration. Disclosures: Schlenk: Novartis: Research Funding; Amgen: Research Funding; Chugai: Research Funding; Pfizer: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Ambit: Honoraria. Off Label Use: Pomalidomide in Myelofibrosis. Reiter:Sanofi: Honoraria. Gattermann:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Hochhaus:Novartis: Consultancy, Honoraria, Research Funding, Travel Other; BMS: Consultancy, Honoraria, Research Funding; ARIAD: Consultancy, Honoraria; Pfizer: Consultancy. Platzbecker:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Heidel:Novartis Inc.: Research Funding; Novartis Inc.: Honoraria.

Background In recent phase-I/II studies, pomalidomide (POM) has shown activity in myelofibrosis (MF) patients (pts) with anemia and/or thrombocytopenia. In the first cohort of the German multicenter MPNSG 01-09 phase-II trial, 38 MF pts were treated with POM 2 mg QD +/- prednisolone (PRED); 34% responded according to IWG-MRT criteria or became RBC-transfusion independent (Schlenk et al., ASH 2012). Additional 58 MF pts were treated in the second study cohort with POM 0.5 mg QD +/- PRED. Main inclusion criteria were age >50y, RBC-transfusion-dependency or Hb Aims To explore the presence of copy number alterations (CNAs), uniparental disomies (UPDs) and MPN-related gene mutations in the 01-09 study cohort and to correlate genetic parameters with treatment response. Methods Affymetrix 6.0 SNP arrays were used for genome-wide screening of CNAs and UPDs in 91% (87/96) of pts. Frequently mutated genes were analyzed in all pts using PCR-based techniques and sequence analysis of coding exons: JAK2 V617F, MPL W515L, ASXL1 (exon 12), EZH2 (exon 2-20), IDH1/2 (exons 4), SRSF2 (exon 1-2), and TP53(exon 4-10). Results In total, 78 CNAs were identified by SNP array analysis. The overall frequency of CNAs was 52% (45/87 pts); 24% (21 pts) showed ≥2 CNAs, while 7% (6 pts) had a complex genotype defined by ≥3 genomic aberrations. Recurrent large (>5 Mb) gains were trisomy 8 (7%; n=6), gain 1q, and trisomy 9 (5% each; n=4), whereas recurrent large losses were identified in 20q (11%; n=10), 5q (8%; n=7), 13q (7%; n=6), 7q/7 (6%; n=5), and 12p/12 (2%; n=2). Moreover, 20% (17/87) of pts showed 19 informative micro-deletions ( Large UPDs (>10 Mb) affecting a terminal end of the chromosome were present in 32% (28/87) of pts. The most frequent UPDs occurred in 9p including JAK2 (17%; n=15). Other recurrent UPDs mapped to 1p (5%; n=4), 4q, and 7q (2% each; n=2). UPDs in 9p were associated with JAK2 V617F in all pts, whereas 75% (3/4) of pts with UPD in 1p were MPLW515L mutated. Mutations in JAK2 (V617F) and MPL (W515L) were present in 55% (53/96) and 6% (6/96) of pts, respectively. The mutation frequencies for the remaining genes were 30% (ASXL1; n=29/96), 9% (SRSF2; n=9/96), 5% (EZH2; n=5/96), 2% (TP53; n=2/96), and 1% (IDH2; n=1/96). Taken together, at least one mutation was found in 79% (76/96) of pts, whereas 21% (20/96) of pts lacked any of these mutations; 28% (27/96) of pts showed ≥2 concurrent mutations. To evaluate genetic differences and predictive factors, pts were separated into a responder (R, n=23) and a non-responder (Non-R, n=73) group. Regarding DIPSS, Non-R pts were not associated with higher risk compared to R pts: 27% (20/73) high risk vs. 17% (4/23) (p=0.334), 61% (44/73) intermediate-II risk vs. 79% (18/23), and 12% (9/73) intermediate-I vs. 4% (1/23) (p=0.275). However, the overall frequency of CNAs was in trend higher in the Non-R group: 56% vs. 39% (p=0.159). Since the total number of genomic losses was similarly distributed (27% vs. 29%), the difference was mainly due to the higher frequency of large genomic gains/trisomies: 4% (R) vs. 22% (Non-R) (p=0.083). UPDs were similar frequent in R and Non-R pts (26% vs. 34%) (p=0.466). The total number of gene mutations was not different between both groups (n=25 in 23 R pts vs. n=77 in 73 Non-R pts) (p=0.475). However, genetic alterations being associated with unfavourable outcome were enriched in the Non-R group: ASXL1 mutation (39% vs. 22%), EZH2 mutation (5% vs. 0%), loss in 5q (30% vs. 4%), trisomy 8 (9% vs. 0%), 12p / ETV6 deletion (6% vs. 0%), 17p deletion / TP53 mutation (3% vs. 0%), and complex genotype (7% vs. 0%). Taken together, adverse genetic alterations were significantly more frequent in Non-R pts compared to R pts: 48% (35/73) vs. 22% (5/23) (p=0.026). Of note, adverse genetic alterations indicated high risk according to DIPSS in no more than 50% (12/24) of the pts. Conclusion Our study on a well-defined patient cohort with advanced MF revealed a high frequency of genetic alterations reflecting the molecular complexity of the disease. Pts with adverse genetic alterations identified by SNP-array and mutation analyses were not sufficiently represented by DIPSS and showed inferior response to POM +/- PRED. Disclosures: Reiter: Sanofi: Honoraria. Gattermann:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Platzbecker:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Hochhaus:Novartis: Consultancy, Honoraria, Research Funding, Travel Other; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Ariad: Consultancy, Honoraria. Schlenk:Amgen: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Chugai: Research Funding; Ambit: Honoraria.

Abstract 2840 Background: Pomalidomide in a single arm phase-I/II study and one randomized four arm phase-II study in primary myelofibrosis (MF) and post-polycythemia vera/essential thrombocythemia (post-PV/ET) MF showed efficacy in particular with respect to improvement in anemia. To date, pomalidomide has been evaluated in MF at two dose levels, 0.5mg and 2.0 mg/day. Aims: To evaluate clinical efficacy of pomalidomide alone and in combination with prednisolone (PRED) in patients with primary or post-PV/ET MF and cytopenia. Methods: The main inclusion criteria for primary or post-PV/ET MF patients were red blood cell (RBC)-transfusion-dependence or hemoglobin =50 years were eligible. Treatment consisted of pomalidomide (POM) 2mg/day; prednisone (PRED) 30mg/day was added in patients who did not respond (≤ stable disease) within three months of therapy. The primary endpoint was response assessed by IWG criteria and extended by the criterion red blood cell transfusion-independence (Gale RP et al., Leuk Res. 2011). Concurrent hydroxyurea in patients with proliferative disease and aspirin 100 mg/d in patients with platelets between 50/nl and 1000/nl were administered. The statistical design of the study was based on the Simon optimal two-stage design. Here we report on the first stage of the study. Median follow-up according to the method of Korn was 18 months. Results: Thirty-eight patients were treated with POM 2 mg/d, the median age was 71 years (range 51–83), 34% were female. Twenty-seven had primary and 11 post-PV/ET MF. Disease stage at study-entry according to the DIPSS was high-risk in 13 (34%), intermediate-2 risk in 22 (58%) and intermediate-1 risk in 3 (8%). Incidence of high-risk cytogenetics, JAK2 V617F mutation and MPL W515L mutation were 29% (10/34), 55% (21/38) and 18% (7/38), respectively. Twenty-seven patients (71%) were RBC-transfusion- and 7 (18%) platelet-transfusion dependent. Median duration of treatment with POM was 11.4 months with 5 patients continue on treatment 24+ months. PRED was added after 3 months in 19 of 28 eligible patients. POM dose-reduction (n=8, 1mg/d; n=2, 0.5mg/d) was performed after a median time of 34 days (range 3–308 days) due to fatigue (n=2), thrombo- and/or neutropenia (n=7), rash (n=1). Seven patients with high risk characteristics (n=6 RBC-transfusion dependent, n=4 high risk cytogenetics) experienced transformation into blast phase (BP), the actuarial probability of transformation to BP measured from diagnosis was 6.0% (SE 4.1%) at 2 years and 22.4% (SE 8.4%) at 5 years. Response was observed in 14 patients (37%) after a median time of 4.8 months (n=1 complete remission, n=5 clinical improvement-platelets, n=3 clinical improvement-erythrocytes, n=5 red cell transfusion-independence); 8 responders received concomitant PRED and responded after a median of three months (range 0.8–11.7 months) of the addition of PRED. In 5 of 14 responders POM dose was reduced due to toxicity, notably before response occurred. Responses were observed within the first 3 months (n=4), between month 4 to 6 (n=4) and beyond month 6 (n=6) with the latest response seen at 12.7 months. There was no correlation between response and JAK2/MPL mutation status or cytogenetics. Basophilia defined as greater than 50% increase in absolute basophil count at month 3 was in trend associated with response (p=0.06). Conclusions: POM with or without PRED in patients with different risk groups of patients with primary and post-PV/ ET MF was effective with a response rate of 37%. Based on results of this first cohort the protocol was amended; i) POM dose has been adjusted to 0.5 mg/d, ii) up-front randomization of PRED at month 4 or month 7 in patients without response but stable disease to single agent POM was introduced. Disclosures: Schlenk: Celgene: Research Funding. Off Label Use: Pomalidomide is so far not approved for the treatment of primary and secondary myelofibrosis.