A new direct-to-drug screening process for multiple myeloma is the latest tool in an ever-increasing push toward precision oncology. Researchers at Mayo Clinic in Scottsdale, Arizona, created an assay to evaluate US Food and Drug Administration (FDA)-approved oncology drugs for personalized sensitivity to solve the problem of not having a good way to predict which patients will benefit from which drugs. The protocol is elastic enough to include new drugs as they become available, and to nix the screening of drugs that aren’t providing much information, making it a promising way to nimbly respond to patient needs as available treatments change.
According to a study published in Blood Cancer Journal, the panel evaluated 76 FDA-approved drugs against 25 ex vivo multiple myeloma cell lines and 113 primary multiple myeloma samples, taking into account sensitivities associated with “clinical phenotype, cytogenetics, DNA mutational profiles, and RNA expression.” Additionally, researchers documented ancillary patient demographics for all samples, such as disease staging and prior drug exposure. From these data, researchers were able to identify patterns of drug sensitivity among patients that fell along genetic and mutational lines. Among the most significant findings were that proteasome inhibitors, dinaciclib, selinexor, venetoclax, auranofin, and histone deacetylating agents caused the broadest cell toxicity in primary multiple myeloma samples, while cells from patients with new diagnoses were overall less sensitive, but especially so to bromodomain inhibitors and inhibitors of receptor tyrosine kinases or non-receptor kinases.
“Direct to drug strategies enable precise testing of a panel of drugs in patient tumor cells, as single agents or combinations,” explained co-lead author Nathalie Meurice, PhD. “Early identification of efficacious therapeutics can guide therapeutic decisions, therefore avoiding treatments with presumably no benefit.”
Using individualized ex vivo sensitivity screening is not itself a new idea in oncology, but has not yet found great success in multiple myeloma research. Because multiple myeloma is highly heterogeneous, and not understood as well as other cancers, it’s been particularly difficult to target therapies. Additionally, not enough drugs were evaluated in previous studies, so the findings were unable to adequately support a personalized treatment. “It is important to screen both a large number of samples, and a large number of drugs,” said co-author Leif Bergsagel, MD.
There are a large number of therapies currently available to clinicians who treat patients with multiple myeloma, and without a better understanding of how each treatment plays with each varied presentation of such a heterogeneous illness, unintended outcomes such as off-target cell toxicity are possible. “Ex vivo drug screening approaches have the potential to identify drugs that are unlikely to result in clinical benefit, avoiding their use and consequent adverse events,” said co-lead author Cecilia Bonolo de Campos, DVM, MSc, PhD.