High Rate of Disease Progression in Low-Risk Myelofibrosis Patients

In the MOST study, the rate of disease progression among patients with low- or intermediate-risk myelofibrosis appeared to increase over time. Myelofibrosis is a rare type of blood cancer that affects the bone marrow’s ability to produce blood cells. Cohort A, comprising patients aged over 65 years alone, had a total of 205 patients deemed low or INT-1 risk, with the most common progression criteria being hemoglobin below 10 g/dL. Further analysis revealed that most patients in cohort A were receiving MF-directed therapy at the time of enrollment regardless of whether they experienced disease progression. The study’s laboratory-defined criteria for disease progression included hemoglobin below 10 g/dL, platelet count below 100 × 10^9/L, less than 1% blasts, white blood cell count above 25 × 10^9/L, and leukemic transformation with greater than 20% blasts.

Criteria for Disease Progression

Physician-reported criteria for progression include constitutional symptoms such as weight loss, fever, and sweats, new or worsening splenomegaly, 1 red blood cell transfusion during the study, physician-reported leukemic transformation, and death due to disease progression. Importantly, the rate of progression appeared to increase over the course of the study. The presence of at least 1 criterion was considered disease progression. Other progression criteria met in cohort A included a platelet count below 10 × 10^9/L in 31.7%, constitutional symptoms in 30.8%, and splenomegaly in 28.3%. Hemoglobin below 10 g/dL was present in 21 of 29 patients (72.4%) of those who had 3 or more progression criteria.

Mutation Analysis

Of all patients enrolled in both cohorts, 186 were tested for at least 1 known driver mutation. In cohort A, 108 of 158 had a JAK2 mutation, and 66 of 93 patients had disease progression whereas 42 of 65 without progression had the JAK2 mutation. Of those evaluated for CALR mutation, 33 of 44 had a mutation with 16 of the 21 with disease progression having it and 17 of the 23 without progression having the mutation present. Five out of 31 had an MPL mutation, with 1 out of 6 having the mutation among those who experienced disease progression and 2 of 10 having it among those who did not experience disease progression.

Cohort B

In cohort B, 27 patients considered low or INT-1 risk for factors other than age only were evaluated. The median time from diagnosis to enrollment was 1.9 years, and the median duration of enrollment was 4.3 years. In cohort B, the percentage of patients with disease progression was 29.6% (n = 8).

Combination Therapy for Hormone Receptor–Positive, HER2-Positive Breast Cancer

Combining anastrozole with palbociclib, trastuzumab, and pertuzumab as a frontline therapy for hormone receptor–positive, HER2-positive breast cancer may avoid some of the toxicities associated with chemotherapy, says Amy Tiersten, MD. Hormone receptor–positive, HER2-positive breast cancer is a type of breast cancer that tests positive for hormone receptors and HER2 protein. This type of breast cancer may grow more quickly than other types. By combining anastrozole with palbociclib, trastuzumab, and pertuzumab, it may be possible to avoid the toxicities associated with chemotherapy while still effectively treating the cancer.

Originally Post From https://www.cancernetwork.com/view/lower-risk-myelofibrosis-population-has-high-disease-progression-rate

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