“One of our goals with maintenance treatment is to have less negative impact on patients’ quality of life,” said Banerjee. “Seeing the results of this survey, we’re already trying to brainstorm ways we can simplify their care,” like decreasing the frequency of in-person visits.
Unlike some institutions, Fred Hutch already allows patients on lenalidomide (a common immunomodulatory drug for multiple myeloma) who could become pregnant to do regular pregnancy tests at home instead of coming to the clinic. (The tests are required because lenalidomide may theoretically cause birth defects.) Next, researchers will be considering additional ways to reduce the time patients spend on care, such as requiring less frequent lab monitoring or reducing the frequency of other medicines these patients may take.
See the abstract: Financial Toxicity and Time Toxicity in Multiple Myeloma: Prevalence, Predictors, and Impact on QOL
Survival rates hold steady with dexamethasone dose reduction
“If you ask patients with multiple myeloma, 100% will say they hate dexamethasone the most of all their medications,” said Banerjee, due to side effects like anxiety and insomnia. The use of this steroid is also linked with cataracts, according to recently published research from Fred Hutch.
Dexamethasone has typically been given at a dose of 40 milligrams once a week during the induction phase of multiple myeloma treatment. Because it does work to treat the disease, this regimen was a reasonable one when we had fewer treatment options, Banerjee said. But now we have more options.
“So,” he said, “we need to be asking, ‘Are these steroids really necessary anymore?’”
In practice, physicians often reduce the dose to 20 mg per week or lower, or stop dexamethasone altogether during induction for patients struggling with the drug’s side effects. However, to definitively support dose reduction as a safe practice, researchers need data on outcomes for patients getting the full dose versus a reduced dose.
Analyzing data from two previous randomized clinical trials by the SWOG Cancer Research Network, Banerjee and a group of researchers from around the country compared two groups of patients. Everyone in the studies completed eight three-week cycles of induction or six four-week cycles. The “full-dose” group stayed on the same dose of dexamethasone throughout. The “lowered” group (76% of the patients) had their dose reduced during induction. Results showed no difference in progression-free survival or overall survival after induction between the groups.
“Those on the full dose versus a lowered dose had identical PFS and OS curves,” said Banerjee.
In their abstract for the ASH conference, the researchers concluded, “These results strongly suggest that maintaining [dexamethasone] 40 mg weekly for the entirety of [newly diagnosed multiple myeloma] induction may be unnecessary in the modern era.”
“Now we’re working on strategies to prospectively study whether we can stop dexamethasone sooner, after just one to two months,” Banerjee said.
See the abstract: Impact of Dexamethasone (Dex) Dose Strength on Outcomes in Newly Diagnosed Multiple Myeloma (NDMM): A Secondary Analysis of SWOG Studies S0777 and S1211
Time for change: shifting the standard of care
Research shows the once-weekly chemotherapy drug bortezomib works as well as a twice-weekly regimen against multiple myeloma but with less risk for the common cancer treatment side effect peripheral neuropathy.
And physicians have taken notice.
In clinic, many providers have moved from prescribing the medicine (which is as an injection) from twice a week to once a week. However, the same shift has yet to occur in clinical trials, where twice-weekly dosing remains common.
“There’s a discrepancy between real life and trials,” said Banerjee — a discrepancy with important implications. For one thing, studies that continue to use twice-weekly dosing aren’t investigating what many patients actually receive. In addition, these studies take more of patients’ time and put them at greater risk for peripheral neuropathy with no added benefit.
To help shift ideas about the standard of care — and thus which clinical trial regimens the pharmaceutical industry will support and which the U.S. Food and Drug Administration will approve — Banerjee and colleagues in the U.S., India and Australia surveyed physicians. They asked more than 200 hematologist-oncologists in 38 countries about their attitudes and perceptions of bortezomib dosing. Each had treated at least one multiple myeloma patient in the previous 12 months.
More than 90% of the physicians preferred once-weekly dosing and more than 90% reported that their patients prefer this, too. A large majority said it was associated with comparable durations of response (79%) and less peripheral neuropathy (89%) compared to twice-weekly dosing.
A sister study on real-world bortezomib prescribing patterns and outcomes bolsters the push to give the drug only once a week. Looking at data from more than 2,500 patients’ electronic medical records, researchers including Banerjee and Fred Hutch’s Andrew Cowan, MD, found no statistically significant difference in progression-free survival or overall survival in patients getting bortezomib once a week versus twice a week.
“Often in research we’re looking for a difference in how well two regimens work: One is better than the other,” explained Banerjee. “Here, we were looking for no difference. And that’s what we found.”
He and his colleagues hope that their work will help change the standard of care for multiple myeloma patients.
“We hope that the FDA will look at this work and recognize that once-weekly bortezomib is the standard of care because it’s what we do in real life,” Banerjee said. “And once-weekly is clearly better for patients. It’s also more ethical. I would not feel comfortable putting a patient in a clinical trial with a twice-weekly regimen, I would not feel comfortable putting a family member on it, because the question is already settled. Twice weekly puts patients at risk unnecessarily. It’s time to break from the past. The time for change is now.”
See the abstract: Standard-of-Care Bortezomib Dosing in Multiple Myeloma: An International Survey of Physicians
Read in Blood Cancer Journal: Once-Weekly Bortezomib as the Standard of Care in Multiple Myeloma: Results from an International Survey of Physicians
Other research to which Banerjee contributed that will be presented at ASH 2023 includes:
Learn more about Fred Hutch research at ASH 2023.
