A Study of Real-world Use and Effectiveness of Cytoreductive Strategies for the Treatment of Second-line Polycythemia Vera in France

Dose modifications were categorized as an increase or decrease in dose.

Timing of bone marrow biopsy was categorized as:

• Prior to first-line treatment
• Prior to second-line treatment

Timing of bone marrow biopsy was categorized as:

• During second-line treatment
• After second-line treatment

Hematocrit control was defined as hematocrit < 45% with the absence of phlebotomy eligibility during the last 3 months.

Proportion of patients achieving clinicohematologic response according to the European LeukemiaNet (ELN) criteria (complete or partial).

Complete clinicohematologic response was defined by:

• Hematocrit < 45% without phlebotomies during the last 3 months, and
• Platelet count ≤ 400 x 10^9/L, and
• White blood cell count ≤ 10 x 10^9/L, and
• Normal spleen size evaluated by physical examination and/or by imaging.

Partial clinicohematologic response was defined by:

In patients who do not fulfill the criteria for complete response, hematocrit < 45% without phlebotomy for 3 months OR response in 3 of the other criteria.

Proportion of patients achieving symptom response according to the ELN criteria. Symptom response is defined as an absolute 10-point improvement in the Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS).

The MPN-SAF TSS (or MPN-10) is a validated patient-reported questionnaire that measures symptom burden in patients with myeloproliferative neoplasms. The instrument assesses 10 key disease-related symptoms, each scored from 0 (absent) to 10 (worst imaginable), generating a total score ranging from 0 to 100. Higher scores indicate greater symptom burden, and changes in the score are commonly used to evaluate clinical benefit and treatment response in both clinical practice and clinical trials

Proportion of patients achieving molecular response according to the ELN criteria (complete or partial).

Complete molecular response was defined by the reduction of any specific molecular abnormality to undetectable levels.

Partial molecular response was defined by:

• A reduction of ≥ 50% from baseline value in patients with < 50% mutant allele burden at baseline OR
• A reduction of ≥ 25% from baseline value in patients with ≥ 50% mutant allele burden at baseline.

Disease progression events include acute myeloid leukemia, myelofibrosis, and PV related death.

Thromboembolic and hemorrhagic events include arterial thrombotic, venous thrombotic, and hemorrhage.

Medical conditions include cancer, autoimmune disease, and opportunistic infection.

Emergency treatments/procedures include antiplatelet drugs, anticoagulants, and phlebotomies.

PV symptoms include splenomegaly, pruritus, fatigue, and bone pain.

The MPN-SAF TSS (or MPN-10) is a validated patient-reported questionnaire that measures symptom burden in patients with myeloproliferative neoplasms. The instrument assesses 10 key disease-related symptoms, each scored from 0 (absent) to 10 (worst imaginable), generating a total score ranging from 0 to 100. Higher scores indicate greater symptom burden, and changes in the score are commonly used to evaluate clinical benefit and treatment response in both clinical practice and clinical trials.

Mutant allele burden is a molecular measure that quantifies the proportion of cells harboring a specific disease-associated mutation (e.g., JAK2 V617F, CALR, or MPL) within a patient sample. It is usually reported as the variant allele frequency (VAF), representing the percentage of mutant alleles among all alleles analyzed, and serves as an indicator of the size of the malignant clone in myeloproliferative neoplasms (MPNs). Changes in mutant allele burden may provide insight into the biological activity of the disease and the molecular effects of therapy.

Mutant allele burden was categorized as ≥ 50% or < 50%.

Pre-specified adverse events of special interest include thrombocytopenia, anemia, neutropenia, infection, weight gain, psychological disorders, nonmelanoma skin cancer, skin disorders, and autoimmune disorders.