Browsing by Author "Ramasamy, Karthik"

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    Myeloma Genome Project Panel is a Comprehensive Targeted Genomics Panel for Molecular Profiling of Patients with Multiple Myeloma
    (American Association for Cancer Research, 2022) Sudha, Parvathi; Ahsan, Aarif; Ashby, Cody; Kausar, Tasneem; Khera, Akhil; Kazeroun, Mohammad H.; Hsu, Chih-Chao; Wang, Lin; Fitzsimons, Evelyn; Salminen, Outi; Blaney, Patrick; Czader, Magdalena; Williams, Jonathan; Zaid, Mohammad I. Abu; Ansari-Pour, Naser; Yong, Kwee L.; van Rhee, Frits; Pierceall, William E.; Morgan, Gareth J.; Flynt, Erin; Gooding, Sarah; Abonour, Rafat; Ramasamy, Karthik; Thakurta, Anjan; Walker, Brian A.; Medicine, School of Medicine
    Purpose: We designed a comprehensive multiple myeloma targeted sequencing panel to identify common genomic abnormalities in a single assay and validated it against known standards. Experimental design: The panel comprised 228 genes/exons for mutations, 6 regions for translocations, and 56 regions for copy number abnormalities (CNA). Toward panel validation, targeted sequencing was conducted on 233 patient samples and further validated using clinical FISH (translocations), multiplex ligation probe analysis (MLPA; CNAs), whole-genome sequencing (WGS; CNAs, mutations, translocations), or droplet digital PCR (ddPCR) of known standards (mutations). Results: Canonical immunoglobulin heavy chain translocations were detected in 43.2% of patients by sequencing, and aligned with FISH except for 1 patient. CNAs determined by sequencing and MLPA for 22 regions were comparable in 103 samples and concordance between platforms was R2 = 0.969. Variant allele frequency (VAF) for 74 mutations were compared between sequencing and ddPCR with concordance of R2 = 0.9849. Conclusions: In summary, we have developed a targeted sequencing panel that is as robust or superior to FISH and WGS. This molecular panel is cost-effective, comprehensive, clinically actionable, and can be routinely deployed to assist risk stratification at diagnosis or posttreatment to guide sequencing of therapies.
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    Treatment Patterns, Survival, Quality of Life, and Healthcare Resource Use Among Patients With Triple-Class Refractory Multiple Myeloma in US Clinical Practice: Findings From the Connect MM Disease Registry
    (Elsevier, 2023) Lee, Hans C.; Ramasamy, Karthik; Weisel, Katja; Abonour, Rafat; Hardin, James W.; Rifkin, Robert M.; Ailawadhi, Sikander; Terebelo, Howard R.; Durie, Brian G. M.; Tang, Derek; Joshi, Prashant; Liu, Liang; Jou, Ying-Ming; Che, Min; Hernandez, Gabriela; Narang, Mohit; Toomey, Kathleen; Gasparetto, Cristina; Wagner, Lynne I.; Jagannath, Sundar; Medicine, School of Medicine
    Background: Adults with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognosis, but the burden of TCR MM has not been well characterized. This study evaluated treatment patterns, overall survival (OS), health-related quality of life (HRQoL), and healthcare resource use (HCRU) among patients with TCR MM in US clinical practice. Patients and methods: Patients with TCR MM in the Connect MM Registry (NCT01081028; a large, US, multicenter, prospective observational cohort study of patients with newly diagnosed MM) were included. Patient characteristics, treatment patterns, HRQoL, and HCRU were analyzed using descriptive statistics. OS was calculated using Kaplan-Meier methodology for the overall cohort and for patients with/without ≥1 post-TCR line of therapy (LOT). Results: A total of 232 patients with TCR MM were included; 155 (67%) had ≥1 post-TCR LOT (post-TCR-Treated subgroup; median 9.9 months of follow-up). Most common post-TCR treatments were carfilzomib (47%), pomalidomide (40%), and daratumumab (26%); median treatment duration was 3.3 months. Median OS was 9.9 months in the overall population, 10.8 months in post-TCR-Treated patients, and 2.6 months for those with no new post-TCR LOT. HRQoL deteriorated and pain increased over 1 year of follow-up, with clinically meaningfully changes in EQ-5D (mean, -0.06 points) and FACT-G (mean, -9.9 points). 124 (53%) patients had ≥1 all-cause hospitalization and 58 (25%) had ≥1 MM-related hospitalization; median annualized length of stay was 35.3 and 42.9 days, respectively. Conclusion: The burden of TCR MM is substantial, emphasizing the need for more effective treatment options in the TCR setting.