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Genomic Mechanism of Resistance Among Patients With Newly Diagnosed Multiple Myeloma Treated With Immunotherapy
Francesco Maura, MD, Myeloma Division, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, investigated the use of whole genome sequencing to help predict patients with newly diagnosed multiple myeloma who may fail to achieve sustained minimal residual disease negativity through unknown resistance mechanisms.
This study was presented at the 64th ASH Annual Meeting in New Orleans, LA.
Transcript:
My name is Francesco Maura, I'm an assistant professor at University of Miami Sylvester Comprehensive Cancer Center.
At this ASH, we presented 2 abstracts. The first, we investigated the genomic mechanism of resistance in patients treated with immunotherapy with newly-diagnosed multiple myeloma. These patients were treated with a combination of drugs called Dara-KRd; that included daratumumab and anti-CD38 monoclonal antibodies, carfilzomib, revlimid, and dexamethasone.
These cycles had been published 2 years ago in Journal of Oncology and show a high rate of MRD negativity in patients without transplant. The rate was 70%. Unfortunately, a fraction of patients did not achieve sustained negativity, lost sustainable negativity, or eventually progressed.
We investigate using whole genome sequencing, which are the key genomic mechanism resistance that might help to predict these patients. That is important because identifying these patients will allow us to investigate alternative and eventually more effective strategies.
What we found is a complex method of genomic alteration, including known features like deletion of 1p, but also new features like Ikaros deletions or large trismus that seems to be involved in certain pathway or genes that are not just responsible for resistance to daratumumab and CD38 monoclonal antibody, but also responsible for other drug, including daratumumab, such as revlimid.
The study overall confirms and highlights the importance of comprehensive investigation within clinical trials. In particular, using whole genome sequencing in order to identify the comprehensive catalog of genomic drivers involved in the resistance, and decipher this complex network of different drivers involving different drugs that cooperate together affecting outcome in our patients.
