Site Editors
Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Posted: Tuesday, October 11, 2022
Using data from two clinical trials—CoMMpass and CARDAMON—Ieuan Walker, MBBS, of Cambridge University Hospitals NHS Trust, United Kingdom, and colleagues employed whole-exome sequencing and applied machine learning programs to create a mutational signature that caters to carfilzomib-related outcomes in patients with multiple myeloma. The results of this study, which suggest that an absence of mutations in five genes may predict response to carfilzomib, were presented during the 2022 International Myeloma Society (IMS) Annual Meeting and Exposition (Abstract OAB-018).
“We present a simple prediction model for response to carfilzomib-based therapy in newly diagnosed myeloma. It is not a general prognostic signature, but rather is specific to carfilzomib,” concluded the study authors. “Being mutation-based, it could be easily applied in the clinic by adding the genes to a targeted exome-sequencing panel.”
The investigators initially focused on 141 patients with multiple myeloma from the CARDAMON trial (ClinicalTrials.gov identifier NCT02315716) who received carfilzomib, cyclophosphamide, and dexamethasone (KCd) with maintenance carfilzomib. Afterward, participants underwent whole-exome sequencing of baseline CD138-positive cells.
The frequency of copy number changes and mutations across the population were common for a multiple myeloma cohort. Of note, a mutational signature demonstrating an absence of mutations in genes MGAM, CCDC168, PDXDC1, ABCC1, and S1PR2 seemed to correlate with improved outcomes with KCd treatment. Additionally, with a gene signature accuracy of 72%, these genes did not appear to be targets of known driver mutations or associated with them.
When this signature was applied to 154 patients in the CoMMpass study (NCT01454297) who were administered upfront carfilzomib-based therapies, individuals classified as responsive to carfilzomib demonstrated a median progression-free survival of 58.8 months. In contrast, those who were less responsive to carfilzomib treatment had a significantly lower median progression-free survival of 33.2 months (P = .0067). Furthermore, the carfilzomib-specific signature did not separate patients treated with first-line cyclophosphamide plus dexamethasone with or without bortezomib.
Disclosure: Disclosure information was not provided.
2022 IMS Annual Meeting and Exposition
