(PA-274) Retrospective Analysis of Molecular Profile of Plasma Cell Myeloma at Diagnosis

Introduction:  Plasma cell myeloma is a malignant disorder characterized by clonal proliferation of bone marrow plasma cells. Somatic mutations frequently occur as secondary events in the development of plasma cell myeloma. Common recurrent mutations implicated in plasma cell myeloma include those involving KRAS, NRAS, BRAF and TP53 genes and they are potentially targetable with new therapeutics.

The primary objective was to determine the prevalence of the NRAS, KRAS, BRAF and TP53 mutation in newly diagnosed plasma cell myeloma patients. The secondary objectives included (i) analysis of the progression free survival (PFS) and overall survival (OS) of the RAS/BRAF mutated group and the unmutated group and (ii) the baseline prognostic factors on PFS and OS in newly diagnosed plasma cell myeloma patients

Methods:   This is a retrospective cohort study of 33 patients aged between 18-65 year-old who were diagnosed with symptomatic plasma cell myeloma between January 2017 to December 2022 in Princess Margaret Hospital. DNA from bone marrow was extracted by standard procedures using QIAamp DNA Blood Mini Kit. Next generation sequencing was performed to detect mutations in four commonly mutated genes in plasma cell myeloma (KRAS, NRAS, BRAF and TP53) using a commercial TruSight Tumor 15 sequencing panel according to manufacturer’s protocol.

Results:   14 out of 33 subjects had either KRAS/NRAS or BRAF mutation. 1 patient had TP53 mutation. There was no significant difference in both PFS and OS in RAS/BRAF mutated and unmutated group. Univariate analysis showed receiving ASCT was a favourable factor for both OS and PFS, while the presence of deletion 17p was associated with poorer overall survival. In multivariate analysis, RAS/BRAF mutation did not demonstrate negative impact both on overall survival and progression free survival. Presence of deletion of 17p remained an independent prognostic factor in both OS and PFS. ASCT had a positive impact both on progression free survival and overall survival.

Conclusions:   RAS/BRAF mutation did not show any prognostic effect in PFS and OS in newly diagnosed multiple myeloma patient in this study. Further study will be needed to evaluate its clinical utility in newly diagnosed multiple myeloma patients.