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Abstract Background: MLN FGFR1 comprise rare hematologic neoplasms belonging to the World Health Organization major category of fusion tyrosine kinases typically associated with eosinophilia. MLN FGFR1 may present with chronic or blast phase (CP or BP) involvement of bone marrow (BM) and/or BP involvement of extramedullary disease (EMD) sites. Diagnosis requires t(8;13)(p11;q12) or another translocation involving chromosome band 8p11 that results in constitutive activation of FGFR1. Hydroxyurea, multikinase inhibitors with anti-FGFR1 activity (eg, midostaurin, ponatinib), or intensive multi-agent chemotherapy often lead to partial (PR) or short-lived complete responses (CR); complete cytogenetic responses (CCyRs) are rare. Given the poor prognosis of MLN FGFR1 and the potential for transformation to BP, a primary goal is to achieve deep responses to bridge patients (pts) to allogeneic hematopoietic stem cell transplant (HSCT). Pemigatinib is a selective and potent inhibitor of FGFR1-3 approved in the US, EU, and Japan for the treatment of adults with previously treated, unresectable, locally advanced, or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement. This is an analysis of data from the ongoing FIGHT-203 study of pemigatinib in adults with MLN FGFR1 (NCT03011372). Methods: FIGHT-203 is a phase 2, multicenter trial enrolling pts ≥18 years of age with MLN FGFR1. Initially, pts had to have received ≥1 prior therapy; the starting dosing was pemigatinib 13.5 mg daily (2 wks; 1 wk off). With amendments, pts without prior therapy were also eligible and the starting dose was changed to 13.5 mg daily on a continuous schedule. The primary endpoint is CR rate; secondary endpoints include rates of overall response (ORR CR + PR), CCyR or partial CyR (PCyR), and safety. All primary and secondary endpoints were investigator-assessed according to protocol-defined criteria including modified response criteria for MDS/MPN and modified Lugano criteria for EMD. CCyR and PCyR were defined as 100% or ≥50% reduction in 8p11-rearranged metaphases or cells, respectively, on karyotyping or fluorescence in situ hybridization. Responses were also adjudicated retrospectively by a Central Review Committee (CRC) with CRC-defined criteria based on local lab and radiologic results and central histopathology review; local and central (given priority) cytogenetic results were used by the CRC. Results: At data cutoff (Dec 31, 2020), 34 pts were enrolled and treated (safety population). The average age was 61.2 (range, 36-78) years and 59% were female. The average number of prior therapies was 1.6 (range, 0-6); 3 pts had prior HSCT; 5 were treatment-naive. The longest duration of pemigatinib exposure was 192.4 wks with median dosing duration of 29.3 wks; pts completed a median of 10.0 (range, 2-65) cycles. At data cutoff, treatment was ongoing in 18 pts (53%); reasons for treatment discontinuation (n, %) include bridging to HSCT (6, 18%), progressive disease (5, 15%), adverse event (3, 9%), physician decision (1, 3%), and patient decision (1, 3%). One pt did not have a FGFR1 rearrangement and was excluded from efficacy analysis . Among 33 pts with MLN FGFR1 evaluable for efficacy, the most common FGFR1 fusion partner genes were 13q12/ZMYM2 (45.5%) and 22q11/BCR (24.2%) (Table 1). Response rates by disease categories are shown in Table 2. Two pts had treated MLN FGFR1with a persistent cytogenetic abnormality only (no morphologic disease). Among the 31 pts with BM and/or EMD involvement, CR rates per investigator and CRC assessments were 64.5% and 77.4%, respectively. Among the 33 pts evaluable for CyR, CCyR rates were 72.7% and 75.8%, respectively. Median durations of CR have not been reached. The most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia (68%), alopecia (59%), diarrhea (50%), stomatitis (44%), and anemia (35%). Grade ≥3 TEAEs in ≥10% of pts were anemia (18%), and pain in extremity and stomatitis (both 12%). Conclusions: Pemigatinib is the first therapy to demonstrate durable and high rates of CR and CCyR in pts with MLN FGFR1, most of whom had progressed on prior therapies including intensive chemotherapy or HSCT. The safety profile was consistent with FGFR inhibition with no unexpected toxicities. These results suggest that pemigatinib may offer a long-term treatment option for pts with MLN FGFR1 ineligible for HSCT or may facilitate bridging to HSCT in eligible pts. Figure 1 Figure 1. Disclosures Gotlib: PharmaEssentia: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kartos: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Deciphera: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cogent Biosciences: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Chair for the Eligibility and Central Response Review Committee, Research Funding; Allakos: Consultancy; Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kiladjian: Taiho Oncology, Inc.: Research Funding; PharmaEssentia: Other: Personal fees; Novartis: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. Vannucchi: AbbVie: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Reiter: Abbvie: Membership on an entity's Board of Directors or advisory committees; Deciphera: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; AOP Orphan Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Blueprint Medicines: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding. Shomali: Blueprint Medicines: Consultancy; Incyte: Consultancy, Research Funding. George: Blueprint Medicines: Consultancy; Celgene: Consultancy; Incyte Corporation: Consultancy; Bristol Meyers Squibb: Consultancy. Patel: Astellas: Consultancy; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Incyte: Consultancy. Colucci: Incyte: Current Employment, Current holder of stock options in a privately-held company. Walker: Incyte: Current holder of stock options in a privately-held company, Ended employment in the past 24 months. Zhen: Incyte: Current Employment, Current holder of stock options in a privately-held company. Verstovsek: Genentech: Research Funding; CTI BioPharma: Research Funding; Blueprint Medicines Corp: Research Funding; Celgene: Consultancy, Research Funding; NS Pharma: Research Funding; Ital Pharma: Research Funding; Incyte Corporation: Consultancy, Research Funding; PharmaEssentia: Research Funding; Gilead: Research Funding; AstraZeneca: Research Funding; Promedior: Research Funding; Protagonist Therapeutics: Research Funding; Roche: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; Constellation: Consultancy; Pragmatist: Consultancy. OffLabel Disclosure: Drug - Pemigatinib (INCB054828), a selective and potent inhibitor of fibroblast growth factor receptors 1, 2 and 3. Purpose - To evaluate the efficacy and safety of pemigatinib in patients with myeloid/lymphoid neoplasms with fibroblast growth factor receptor 1 (FGFR1) rearrangement.
Gotlib et al. (Fri,) studied this question.