B025 - ALLOGENEIC STEM CELL TRANSPLANTATION IN PATIENTS WITH BCR-ABL-NEGATIVE MYELOPROLIFERATIVE NEOPLASMS PRETREATED WITH JAK1/JAK2 INHIBITORS (ID 317)
- M. Barabanshikova
- E. Morozova
- I. Moiseev
- J. Vlasova
- V. Baykov
- I. Ushal
- G. Rodionov
- S. Moiseev
- I. Barkhatov
- K. Afanasyeva
- S. Bondarenko
- B. Afanasyev
Primary myelofibrosis (PMF), post-polycythemia vera (post-PVMF), post-essential thrombocythemia (post-ETMF), and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are BCR-ABL-negative hematopoietic stem cell disorders (MPN) with variable prognosis. The aim of the study was to analyze the results of allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients MPNs who did (MF+) and who did not receive (MPN-) target therapy with JAK1/JAK2 inhibitors.
Fifty four patients were included in the study with median age of 49 years (20-61). JAK1/JAK2 inhibitor therapy with ruxolitinib (25) or pacritinib (2) was performed during 7 months before alloHSCT and disease stabilization occurred in 15 patients, disease progression - 4, clinical improvement - 8 according to ELN criteria. Among them 26 patients received ruxolitinib 30-45 mg daily until D-1 and 10-15 mg/day from D+5 to D+100 and graft versus host disease (GVHD) prophylaxis with cyclophosphamide 50 mg/kg D+3,+4. Twenty-seven patients with MPN- (postPV-MF-2, PMF-10, CMML-9, aCML-3, MPN unclassifiable-3) were not treated with target therapy. GVHD prophylaxis in MPN- patients consisted of antithymocytic globulin (ATGAM 60 mg/kg or thymoglobuline 5 mg/kg) and tacrolimus/mophethyl-mycophenolate. All patients received conditioning regimen with fludarabine 180 mg/m2 plus busulfan 8-10 mg/kg. AlloHSCT was performed from unrelated (37), related (10) and haploidentical (7) donor. Stem cell source was granulocyte colony-stimulating factor mobilized peripheral blood progenitor cells (43) and bone marrow (11). Median number of CD34+cells/kg was 6,4 x 109 (1,4-11,9). In 20 patients analysis of ruxolitinib concentration in peripheral blood with high performance liquid chromatography-tandem mass spectrometry (Agilent technology, USA) at D0, D+7, D+14, D+21, D+30, D+60, D+100 was performed.
Median follow up was 32 months (2-126). Primary engraftment was documented in 77% of patients. The rate of primary graft failure was 16% in MF+group and 29% - in MPN- (p=ns).
Analysis of Cthrough concentrations of ruxolitinib demonstrated accumulation of the drug from day+7 (median 17.7 ng/ml) to day+14 (median 43.8 ng/ml, p=0.028) and subsequent stable concentrations. Ruxolitinib value was not detected at day 0 in all samples due to drug intake interruption from day-1 to +4. Five MF+ patients died due to infection (4) and GI-bleeding(1).
Acute GVHD grade 2-4 and chronic moderate/severe GVHD was documented in 20% and 24% MF+, 29% and 43% of MPN-patients (p=ns). Viral reactivation occurred in 42% MPN-, 43% of MF+patients (p=ns). The rate of toxic hepatitis grade 3-4 and venoocclusive liver disease was similar between groups: 21% and 12% in patients with MPN-, 25% and 13% in MF+patients.
The 3-year overall survival was superior in MF+patients 74% compared to MPN- - 30% (p=0.007), as well as progression free survival (66% vs 24%, p=0.016).
Introduction of JAK1/JAK2 inhibitor in the pre- and posttransplant period might be one of the options to improve results of alloHSCT in MF patients.
M.V.B. had received travel grants from Pfizer, Novartis and lecturer fees from Novartis, Celgene. I.S.M. had received travel grants from MSD, Novartis, Pfizer, Celgene, Takeda, BMS, consulting fees from Novartis and Celgene, Novartis. The remaining authors declare no competing financial interests.