Performing a biospy in the hip or sternum may not always provide the whole picture to identify genetic mutations within a single myeloma patient. In fact, the genetic features of a biopsy sample from the hip may be different than taking a sample from a large myeloma focal lesion (bone lesion) somewhere else in the body.
Myeloma researchers recently reported on testing taken before and after treatment to see what changed and how well a general biopsy vs. a localized biopsy differed in assessing genetics.
The researchers performed a study of 13 myeloma patients. They performed standard hip bone marrow biospies and also biopsied large focal lesions using an image-guided method before and after an induction therapy of 4 cycles of carfilzomib, lenalidomide, and dexamethasone (KRd).
The biopsied samples were sorted for myeloma-specific CD138 cells to get more accurate test results, and were then genetically tested.
At initial diagnosis and at the end of treatment, the number of genetic mutations in both the bone marrow and focal lesion biopsy samples had the same overall number of genetic mutations.
The average percent of unique mutations found in the focal lesions compared to the traditional bone marrow biopsy samples was 18.9% at diagnosis and 10.9% at end of treatment, so treatment made a difference in killing some of these genetic clones.
High-risk genetic features (including TP53, MAPK, KRAS, NRAS, BRAF, CKS1B, FAF1, CDKN2C, DIS3, MAF, and MMSET) were found in 30% in the bone marrow biopsies and in 22.2% of the focal lesion biopsies.
Importantly, after treatment no high-risk genetic mutations were found on the regular bone marrow biopsies, while 20% of the focal lesion biopsies still had high-risk genetic mutations. This means that these high risk mutations can still persist after therapy and may not be detected using a normal biopsy process.
In the patients who had earlier biopsy samples with a high-risk genetic mutation identified at diagnosis did not have those high-risk features detected in either their bone marrow or focal lesion biopsies after therapy.
One patient had an ealier biopsy that showed no detectable high-risk genetic mutation at diagnosis. They did develop a high-risk genetic mutation after treatment that was found in their focal lesion biopsy after therapy.
The most high-risk TP53 mutation made up 28.6% of all high-risk mutations detected and were ONLY found on the focal lesion biopsies.
Natalia Neparidze, MD of Yale School of Medicine (and principal investigator of the study) said:
“This is an important study because a couple of these mutations that we noted in the lesions were commonly described as the MYC as well as KRAS and nowadays scientists are developing great new drugs to target this mutation. These mutations may in the future be druggable, so the findings of this study are relevant in terms of future therapeutic implications.”
The key takeaway is that while genetics of the mutations aren't changing significantly before or after induction treatment, a large focal lesion is the better place to test to see if the clone is really gone, rather than a traditional biopsy in the hip. If you have large focal lesions, ask your doctor if they can be tested genetically so you are aware of the type of myeloma you have.
about the author
Eduardo Franco is an International Medical Graduate who Joined HealthTree in 2020 as part of The Patient Experience team. He reads the patient’s medical records and compares them with the information reported by patients on Healthtree so we can have the most exact information on our platform. He is a martial arts practitioner, drummer and avid reader.