Pomalidomide In MPN–associated Myelofibrosis With Cytopenia: Results Of The Mpnsg 01-09 Study
Authors: Schlenk Richard F. , Stegelmann Frank , Reiter Andreas , Jost Edgar , Gattermann Norbert , Hebart Holger , Waller Cornelius F. , Hochhaus Andreas , Platzbecker Uwe , Schafhausen Philippe , Blau Igor W. , Verbeek Walter , Heidel Florian H , Werner Martin , Kreipe Hans , Heiligensetzer Cora , Mack Silja , Ostlender Sabine , Teleanu Veronica , Benner Axel , Döhner Hartmut , Grießhammer Martin , Döhner Konstanze 
Published: October 2019

Abstract

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 <100 g/L and/or platelets <50/nL and/or neutrophils <1/nL. Treatment of the 1st cohort was POM, 2mg/d. PRED, 30mg/d was added in non-responders at 4 months (mo). Treatment of the 2nd cohort was POM, 0.5mg/d. Subjects were randomized to receive PRED, 30 mg/d, starting at 4 or 7 mo in non-responders. The primary endpoint was response assessed by IWG-MRT criteria and RBC-transfusion response (Gale RP et al., Leuk Res. 2011). Patients with proliferative disease could receive concomitant hydroxyurea. Acetylsalicylic acid, 100 mg/d, was given to prevent thrombosis. The study-design used Simon’s optimal 2-stage design for the 1st cohort and a one-stage design for the 2nd cohort.

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 platelets<50/nL were 27% (95%-CI, 10-57%) and 11% (95%-CI, 3-33%; p=0.34). In patients with platelets 50-100/nL, stable platelets>100/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.