Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis with Prior Exposure to Janus Kinase 1/2 Inhibitors.
The impact of Janus kinase (JAK) 1/2 inhibitor therapy before allogeneic hematopoietic cell transplantation (HCT) has not been studied in a large cohort in myelofibrosis (MF). In this retrospective multicenter study, we analyzed outcomes of patients who underwent HCT for MF with prior exposure to JAK1/2 inhibitors. One hundred consecutive patients from participating centers were analyzed, and based on clinical status and response to JAK1/2 inhibitors at the time of HCT, patients were stratified into 5 groups: (1) clinical improvement (n = 23), (2) stable disease (n = 31), (3) new cytopenia/increasing blasts/intolerance (n = 15), (4) progressive disease: splenomegaly (n = 18), and (5) progressive disease: leukemic transformation (LT) (n = 13). Overall survival (OS) at 2 years was 61% (95% confidence interval [CI], 49% to 71%). OS was 91% (95% CI, 69% to 98%) for those who experienced clinical improvement and 32% (95% CI, 8% to 59%) for those who developed LT on JAK1/2 inhibitors. In multivariable analysis, response to JAK1/2 inhibitors (P = .03), dynamic international prognostic scoring system score (P = .003), and donor type (P = .006) were independent predictors of survival. Among the 66 patients who remained on JAK1/2 inhibitors until stopped for HCT, 2 patients developed serious adverse events necessitating delay of HCT and another 8 patients had symptoms with lesser severity. Adverse events were more common in patients who started tapering or abruptly stopped their regular dose ≥6 days before conditioning therapy. We conclude that prior exposure to JAK1/2 inhibitors did not adversely affect post-transplantation outcomes. Our data suggest that JAK1/2 inhibitors should be continued near to the start of conditioning therapy. The favorable outcomes of patients who experienced clinical improvement with JAK1/2 inhibitor therapy before HCT were particularly encouraging, and need further prospective validation.
MPN Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Mohamed
M
Shanavas
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
Uday
U
Popat
Department of Medicine, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Laura C
LC
Michaelis
Department of Hematology and Oncology, Mayo Clinic Cancer Center, Scottsdale, Arizona.
Veena
V
Fauble
Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, United Kingdom.
Donal
D
McLornan
Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, Ohio.
Rebecca
R
Klisovic
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
John
J
Mascarenhas
Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Roni
R
Tamari
Division of Cellular Therapy and Hematologic Malignancies, Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina.
Murat O
MO
Arcasoy
Oxford University Hospitals NHS trust, Oxford, UK.
James
J
Davies
Department of Medicine, Weill Cornell Medical College, New York, New York.
Usama
U
Gergis
Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Oluchi C
OC
Ukaegbu
Center for Cell and Gene Therapy, Baylor College of Medicine and Houston Methodist Hospital, Houston, Texas.
Rammurti T
RT
Kamble
Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
John M
JM
Storring
Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio.
Navneet S
NS
Majhail
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Rizwan
R
Romee
Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms, Department of Leukemia, MD Anderson Cancer Center, Houston, TX, US.
Srdan
S
Verstovsek
Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, United Kingdom.
Antonio
A
Pagliuca
Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, Ohio.
Sumithira
S
Vasu
Department of Hematology and Oncology, Mayo Clinic Cancer Center, Scottsdale, Arizona.
Brenda
B
Ernst
Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Eshetu G
EG
Atenafu
Department of Medicine, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Ahmad
A
Hanif
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
Richard
R
Champlin
Department of Medicine, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Paremeswaran
P
Hari
MPN Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Electronic address: vikas.gupta@uhn.ca.
Vikas
V
Gupta
D000328:Adult; D000368:Aged; D064591:Allografts; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000201:enzymology / Q000401:mortality / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D015996:Survival Rate
D047428:Protein Kinase Inhibitors; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2
Allogeneic transplantation; JAK1/2 inhibitors; Myelofibrosis; Ruxolitinib; Survival