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Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Towards Personalized Medicine in Myeloproliferative Neoplasms and Mastocytosis: New and Repurposed Drugs for Unmet Clinical Needs
Hematology Disease Topics & Pathways:
clinical trials, Research, adult, Clinical Research, Therapies, Adverse Events, Study Population, Human
Key eligibility included the need for cytoreduction, morphologically confirmed pre-PMF, overt PMF, post-polycythemia vera MF (PPV-MF) or post-essential thrombocythemia MF (PET-MF), and DIPSS low/intermediate-1 risk category. The primary outcome was the clinicohematologic complete response (CHCR) rate at 24 and 48 weeks. Secondary outcomes included adverse events (AEs), changes in allele burden of driver genes and other non-driver mutations, changes in quality-of-life (QOL), changes in cytokine profiles and changes in bone marrow morphology. Patients received P1101 at a starting dose of 250mcg followed by 350mcg at week 2 and 500mcg every 2 weeks from week 4 onwards.
At the data cut-off of 28 July 2022, 56 patients (33 men, 23 women) with a median age of 58 (range: 30-87) were enrolled. Thirty eight patients (68%) had pre-PMF, 5 (9%) had overt PMF, 3 (5%) had PPV-MF and 10 (18%) had PET-MF. Next-generation sequencing (NGS) in 53 patients showed JAK2V617F in 39 patients (74%), CALR mutations in 13 patients (25%) and MPL mutation in 1 patient (2%). On day 1, the mean white blood cell (WBC) count, hemoglobin concentration, platelet count, and lactate dehydrogenase (LDH) level were 9.4 x 109/L (range: 3.3-33.95), 12.5 g/dL (range: 7.1-15.9), 520 x 109/L (range: 113-1038) and 359 IU/L (range: 136-1146) respectively.
The median duration of follow-up was 24 (2-28) weeks. Forty-six and 30 patients completed 12 and 24 weeks of treatment respectively. At 12 and 24 weeks the CHCR rate was 74% and 67%, respectively. At 24 weeks, 36 (92%) of 39 JAK2V617F mutated patients had stable or improved JAK2V617F allele burden by droplet digital polymerase reaction (ddPCR). Three patients (8%) had >50% reduction in the JAK2V617F allele burden with one patient achieving undetectable JAK2V617F from week 16 onwards. Disease progression or blastic transformation were not observed during the study. The most common AEs were malaise (N=22, 39%; Grade 1-2, N=21; Grade 3-4, N=1), anemia (N=12, 21%; Grade 1-2, N=8; Grade 3-4, N=4), muscle pain (N=11, 20%; Grade 1-2, N=11; Grade 3-4, N=0) and hair loss (N=10, 18%; Grade 1-2, N=10; Grade 3-4; N=0) . There were no treatment discontinuations, safety signals or deaths related to treatment.
In summary, P1101 was well-tolerated, effective in cytoreduction and induced molecular responses. The recruitment of patients is ongoing.
Disclosures: Kwong: Amgen, Astellas, Bayer, Beigene, Bristol Meyer Squibb, Celgene, Janssen, Merck, Otsuka, Novartis, Roche, Takeda: Consultancy, Speakers Bureau; Novartis, Merck, Bristol Meyer Squibb: Research Funding.
OffLabel Disclosure: Ropeginterferon alfa 2b was used off-label in patients with myelofibrosis in this study.