TY - JOUR
T1 - Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial
AU - Harrison, Claire N.
AU - Nangalia, Jyoti
AU - Boucher, Rebecca
AU - Jackson, Aimee
AU - Yap, Christina
AU - O'Sullivan, Jennifer
AU - Fox, Sonia
AU - Ailts, Isaak
AU - Dueck, Amylou C.
AU - Geyer, Holly L.
AU - Mesa, Ruben A.
AU - Dunn, William G.
AU - Nadezhdin, Eugene
AU - Curto-Garcia, Natalia
AU - Green, Anna
AU - Wilkins, Bridget
AU - Coppell, Jason
AU - Laurie, John
AU - Garg, Mamta
AU - Ewing, Joanne
AU - Knapper, Steven
AU - Crowe, Josephine
AU - Chen, Frederick
AU - Koutsavlis, Ioannis
AU - Godfrey, Anna
AU - Arami, Siamak
AU - Drummond, Mark
AU - Byrne, Jennifer
AU - Clark, Fiona
AU - Mead-Harvey, Carolyn
AU - Baxter, Elizabeth Joanna
AU - McMullin, Mary Frances
AU - Mead, Adam J.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - PURPOSEPolycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms.PATIENTS AND METHODSMAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response.RESULTSOne hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P =.02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P <.001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P =.01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P =.03). Serial analysis of JAK2V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P =.001, EFS P =.001, overall survival P =.01) and clearance of JAK2V617F stem/progenitor cells. ASXL1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P =.003). The safety profile of ruxolitinib was as previously reported.CONCLUSIONThe MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.
AB - PURPOSEPolycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms.PATIENTS AND METHODSMAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response.RESULTSOne hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P =.02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P <.001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P =.01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P =.03). Serial analysis of JAK2V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P =.001, EFS P =.001, overall survival P =.01) and clearance of JAK2V617F stem/progenitor cells. ASXL1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P =.003). The safety profile of ruxolitinib was as previously reported.CONCLUSIONThe MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.
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U2 - 10.1200/JCO.22.01935
DO - 10.1200/JCO.22.01935
M3 - Article
C2 - 37126762
AN - SCOPUS:85162987090
SN - 0732-183X
VL - 41
SP - 3534
EP - 3544
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 19
ER -