Pinpointing Peripheral Blood Blasts and the Impact on OS in Myelofibrosis

Analyzing a large cohort of adult patients with myelofibrosis (MF), researchers are offering a better understanding of how further quantification of peripheral blood (PB) blasts impact outcomes, like overall survival (OS), as well as how ruxolitinib plays a role.

Currently, patients are provisionally considered to have accelerated phase MF if they have 10% to 19% PM/blood marrow (BM) blasts, which has been associated with poorer outcomes. However, the researchers of the current study sought to determine the implications of further subclassifying blasts. The researchers identified 3 groups with distinctive patterns of OS, finding that “PB blast percentages offer additional prognostic value in patients who have <5% BM blasts.”

Among these 3 groups, median OS was 64 months for patients with 0% blasts, which dropped to 48 months for patients with PB blasts from 1% to 3%, and to 22 months for patients with 4% PB blasts. Compared with patients with 1% to 3% PB blasts and patients with 4% PB blasts, patients with 0% PB blasts had hazard ratios of 0.69 (95% CI, 0.58-0.81) and 0.34 (95% CI, 0.27-0.43), respectively.

Overall, the researchers observed that higher percentages of PB blast were negatively associated with hemoglobin and platelets and positively associated with white blood cells, age, presence of symptoms, grade >2 reticulin fibrosis, splenomegaly, and unfavorable and complex karyotypes.

Among the more than 1300 patients included in the study, 53% had 0% PB blasts and <5% bone marrow (BM) blasts.

Results also showed that:

• 88% had 1% to 4% BP blasts, 7% had 5% to 9% PB blasts, and 5% had >10% PB blasts.
• 100% of the patients with >5% PB blasts also had >5% BM blasts, while 14% of patients with 1% to 4% PB blasts had >5% BM blasts.
• 67% and 32% of patients with BM blasts 5% to 9% and 10% to 19% had PB blasts <5% and <10%, respectively.

Notably, the findings indicated that PB blasts had an effect on OS only in patients with <5% BM blasts, while no effect of PB blasts was observed in patients with >5% BM blasts.

The researchers also highlighted their finding that patients with 4% PB blasts and patients with 5% to 9% BM/PM blasts had clinical features that were comparable to those of patients with 10% to 19% blasts; while patients with 4% PB blasts and 5% to 9% BM/PM blasts had longer OS than those with 10% to 19% blasts, the difference was not statistically significant.

Looking at the role of ruxolitinib in these patients, 44% of whom received the treatment, the researchers wrote, “significantly better OS with the receipt of ruxolitinib during the disease course in patients with <10% blasts suggests that RUX has an important role in clinical practice. However, a shorter duration of ruxolitinib benefit in patients with 5% to 9% blasts and the significantly high rate of progression to [acute myeloid leukemia] call for investigations of novel combinatorial approaches in these patients.”

According to the researchers, the inability to determine the role of ruxolitinib in these patients with 5% to 9% blasts was due to the study’s retrospective design, with various ruxolitinib regimens and start times during disease course.

Reference

Masarova L, Bose P, Pemmaraju N, et al. Prognostic value of blasts in peripheral blood in myelofibrosis in the ruxolitinib era. Cancer. Published online July 22, 2020. doi: 10.1002/cncr.33094.