Myeloid/Lymphoid Neoplasms With Fibroblast Growth Factor Receptor 1 Rearrangement: A US Real-World Chart Review

Abstract

Abstract Introduction/Objective Myeloid/lymphoid neoplasms (MLN) with fibroblast growth factor receptor 1 gene (FGFR1) rearrangement (MLNFGFR1) is a rare and aggressive hematologic malignancy characterized by molecular disruption of FGFR1 at the 8p11 locus. This real-world study describes demographic and clinical characteristics, diagnostic testing, and clinical outcomes in patients with MLNFGFR1 in the US. Methods/Case Report Probable MLNFGFR1 cases (n=51) were identified from a retrospective, physician-abstracted (5/29/2020-6/23/2020) chart review of patients within the US Cardinal Health Oncology Provider Extended Network (feasibility survey). In a subsequent full chart review (12/29/2020-3/4/2021), 33 of these probable MLNFGFR1 cases were considered to be confirmed based on additional 8p11/FGFR1 testing result data collected. Descriptive analyses of demographic/clinical characteristics, diagnostic testing, and clinical outcomes of patients with confirmed MLN FGFR1 were performed. Results (if a Case Study enter NA) The mean age at initial MLNFGFR1 diagnosis was 65.9 (SD 13.5) years, 60.6% patients were male, and 63.6% were white. Patients were managed by 12 physicians,10 in community practices. FGFR1 translocations were identified by karyotyping in 72.7% of patients. Rearrangements in FGFR1 were detected by fluorescence in situ hybridization, next generation sequencing, and/or real-time polymerase chain reaction in 66.7%, 21.2% and 6.1% of patients, respectively. FGFR1 rearrangement was detected in bone marrow aspirate and peripheral blood in 90.9% and 9.1% of patients, respectively. Fusion partners ZMYM2 and CPSF6 were reported in 46.2% and 15.4% of patients, respectively, and BCR, CUX1, RANBP2, TPR, and MYO18A were reported in 7.7% of patients each. Conclusion Although rare, patients with MLNFGFR1 do present in US community practice settings. Conventional cytogenetics can identify FGFR1 translocations which can be confirmed by FISH with FGFR1 break-apart probes. NGS can be used to identify cryptic rearrangements when clinical suspicion is high but no rearrangement is present on FISH. In addition to diagnosis, RT-PCR is also useful to assess molecular response.