Colorado tool, My-DST, may pick best multiple myeloma treatment

May 28, 2020

In 1844, multiple myeloma was first treated with a rhubarb pill and an infusion of orange peel. Since then, more than 15 drugs have earned FDA approval to treat multiple myeloma and with so many options, a major question has become what cocktail and sequence is best?

"These days people are going through ten lines of therapy for multiple myeloma and end up getting every drug we have. The question is when," says Daniel Sherbenou, MD, PhD, University of Colorado Cancer Center investigator and assistant professor in the CU School of Medicine Division of Hematology. "Patients' first remission is usually their best one, so you want to use the best drugs first. If you get the right drug first, a patient can be in remission five or more years, and that's the period when quality of life is best, just taking oral medication for their disease. So there's a lot of advantage for getting the sequencing right."

Currently, without a good way to predict which drugs will work, doctors often use three or more agents, hoping that some will offer benefit while assuming that some will not. The use of more drugs often leads to increased drug side effects. And in cases where patients are more frail and side effects are more dangerous (as is often the case in multiple myeloma), doctors and patients may have to pick only one or two drugs and cross their fingers their choices prove useful.

"Right now, the choice between three FDA-approved cocktails really comes down to personal provider preference," Sherbenou says. "In many cases, there's no rational way to choose."

Generally, the many multiple myeloma drugs fall into a few main categories: Drugs that adjust the immune system, proteasome inhibitors, and a relatively new drug, daratumumab, which attaches to a protein called CD38 that is overexpressed on multiple myeloma cells. Now the first paper published by Zach Walker and colleagues from the Sherbenou lab at University of Colorado Cancer Center uses strategies of drug development to predict which classes of drugs will offer the most benefit.

The team took a new approach.

"People have tried this before, but earlier studies purified myeloma cells away from the rest of the tumor. Once these cells are by themselves, their survival takes a dip even without treatment. If you have only 10 percent viability anyway, you only have small window to measure drug effects," Sherbenou says.

Importantly, purifying multiple myeloma cells into a dish takes them away from the immune system, and without the ecosystem of an immune system, it's impossible to test immunotherapies.

"Our approach was to culture whole bone marrow, so you get multiple myeloma cells along with immune system and other cells," Sherbenou says. "It worked much better and we were able to test immunotherapy effects."

Sherbenou calls his test Myeloma Drug Sensitivity Testing (My-DST). Basically, the test incubates liquid biopsies of a patient's disease and then treats the samples with the seven most effective drugs approved to treat multiple myeloma. The approach is especially possible in multiple myeloma, which requires a bone marrow biopsy and not a more invasive solid tumor biopsy to obtain a sample of the cancer for testing. Using 55 patient samples of multiple myeloma, the group was able to show that how well drugs kill cells in these samples predicted how well real patients responded to these drugs in the clinic.

"We were surprised at how well it worked," Sherbenou says.

In addition to using My-DST to help patients and doctors pick the best therapies, Sherbenou hopes to use the test to guide drug development.

"If you develop a new drug for multiple myeloma, the first test won't be with new patients, and they will be multiple-drug resistant. So you need to pinpoint just the patients who are still likely to benefit. We hope My-DST will help predict which drugs are most promising for a phase 1 clinical trials," Sherbenou says.

In addition to the publication of more studies fleshing out the science of My-DST, Peter Forsberg and Tomer Mark of the CU Plasma Cell Disorders Program also designing clinical trials around the test. In one trial, the group hopes to test the ability of My-DST to pick treatments that will benefit patients who have already been treated with multiple lines of therapy; in another trial, the group hopes to use My-DST to choose between the three FDA-approved cocktails for patients' first course of treatment.

"We have such a big menu of options for multiple myeloma - a lot of choices we're trying to distinguish between," Sherbenou says. "By choosing the exact one a patient gets, we hope to get them into a deeper response more rapidly."
-end-


University of Colorado Anschutz Medical Campus

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.