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Cytopenias/Proliferation Define Outcomes for Patients With Primary MF and MF from Essential Thrombocythemia or PV
According to research presented at the 2024 American Society of Clinical Oncology (ASCO) annual meeting, cytopenias and/or proliferation, rather than JAK2V617F (JAK2) allele burden </≥50%, correlate with the outcomes of patients with primary myelofibrosis (PMF) and patients with MF from essential thrombocythemia or polycythemia vera (PPV/PET-MF). In addition, all patients were noted to display improved survival with ruxolitinib treatment.
Myelodepleted MF, which is characterized by cytopenias, lower JAK2 allele burden, and shorter benefit from JAK-inhibitor ruxolitinib, exhibits worse overall survival (OS) compared to myeloproliferative MF. In addition, lower JAK2 and inferior OS is generally more typical for patients with primary MF (PMF) as compared with patients with MF from essential thrombocythemia or polycythemia vera (PPV/PET-MF).
“We sought to investigate the impact of JAK2 (</≥ 50%), cytopenias and the use of ruxolitinib in outcome of PMF/PPV-PET-MF patients from our center,” explained Julie Braish, MBBCh, The University of Texas MD Anderson Cancer Center, Houston, Texas and colleagues.
To determine these results, study authors retrospectively reviewed the medical charts of 601 patients with JAK2-mutated MF (known JAK2%). Patients were divided based on the absence (-) or presence (+) of cytopenias (hemoglobin < 10 g/dL or platelets < 100 x109/L) and leukocytosis (WBC ≥ 25 x109/L) into: grade 1 = (-)/(-) [absence of both]; grade 2 = (-)/(+) [proliferative]; grade 3 = (+)/(-) [cytopenic]; grade 4 = (+)/(+) [cytopenic and proliferative]) and evaluated overall survival (OS) per JAK2 </≥ 50% and PMF vs PPV/PET-MF. Investigators assessed the tolerance of ruxolitinib ≥3 years by utilizing descriptive statistics, Kaplan-Meier curve with log-rank test and regression analysis for demographics, estimation of OS and its comparison.
Results demonstrated that patients with JAK2 <50%, more likely PMF, exhibited more anemia and thrombocytopenia, higher blasts, less leukocytosis, and smaller splenomegaly. Additionally, JAK2 </≥ 50% did not discriminate against the OS of the entire group, PMF or PPV/PET-MF (median OS of around 45 months for each; only PPV/PET-MF with 64 months). The OS of grades 1 to 4 according to JAK2 </≥ 50% and PMF/ PPV/PET-MF and combined OS of patients with comparable outcome (A through D) are as follows: PMF JAK2 < 50%: grade 1, 85 (A); grade 2, 48 (B); grade 3, 35 (C); grade 4, 14 (D) ; PMF JAK2 ≥ 50%: grade 1, 53 (B); grade 2, 37 (C); grade 3, 34 (C); grade 4, 21 (D); PPV/PET-MF JAK2 < 50%: grade 1, 102 (A); grade 2, 91 (A); grade 3, 28 (C); grade 4, 3 (D); and PPV/PET-MF JAK2 ≥ 50%: grade 1, 80 (A); grade 2, 72 (A); grade 3, 36 (C); grade 4, 30 (C).
The final groups with distinct outcomes included: A+B) non-cytopenic PET/PPV-MF and PMF irrespectively of proliferation and JAK2% - with one exception of non-cytopenic, proliferative PMF with JAK2 ≥50% - had median OS of 70 months (range, 54 to 86); D) cytopenic and proliferative PMF with any JAK2% and PPV/PET-MF with JAK2 < 50% of median OS 19 months (range, 13 to 25), and C) the rest of the cytopenic patients and non-cytopenic, proliferative PMF with JAK2 ≥50% with a median OS of 36 months (range, 32 to 42). Among the 3 final groups, a similar proportion of patients were exposed to ruxolitinib during their follow-up: 36% (A+B), 31% (B) and 28% (C), respectively (p =0.13). The most patients in (A+B) group were able to tolerate ruxolitinib for ≥3 years (p =0.036). All patients had improved OS with ruxolitinib.
In conclusion, “Cytopenias and/or proliferation, rather than JAK2 allele burden </≥50%, define the outcome of patients with [primary MF] and with [MF from essential thrombocythemia or PV],” Braish and colleagues stated.
“All patients had improved overall survival with ruxolitinib,” they also noted based on data to be presented.
Source:
Braish J, Bose P, Pemmaraju N, et al. Impact of JAK2 allele burden on MF outcome in the era of ruxolitinib. Presented at the ASCO Annual Meeting. May 31-June 4, 2024; Chicago, IL. Abstract 6514
