Ask any patient (or, perhaps even just as relevant, ask any caregiver) the side effects of dexamethasone are well known and well bemoaned by most. Insomnia, agitation, anxiety, aggression, personality/mood changes, depression, and stomach upset are just a few of the issues that have helped this steroid, commonly referred to as dex, earn its bad reputation.
As a patient (Todd) and caregiver (Diane) team, we have experienced the devilish side effects of dex often since Todd was diagnosed in 2017. We are also HealthTree Myeloma Coaches and speak with patients and their families who often claim that the side effects of dex are among the hardest parts of their myeloma journey. This is particularly true for frail and elderly patients. Unfortunately, these patients are often the ones least likely to advocate for themselves and tell their doctors about side effects. They feel side effects are to be expected and must be endured; they suffer in silence. Based on research presented at ASH 2022, seniors may be able to eliminate dex from their treatment after an initial 8-week period.
Dr. Salomon Manier delivered an oral presentation titled, “A Dexamethasone Sparing-Regimen with Daratumumab and Lenalidomide in Frail Patient with Newly-Diagnosed Multiple Myeloma: Efficacy and Safety Analysis of the Phase 3 IFM2017-03 Trial” (Paper 569). The research offered encouraging news that there may be a safe and effective regimen that is a better option for frail and elderly patients, prescribing dexamethasone only in the first 2 cycles of treatments, and then the treatment continues without dex.
In this phase 3 trial, 295 newly diagnosed multiple myeloma patients over age 65 with significant frailty were randomly assigned to receive a regimen of daratumumab and lenalidomide (DR) or lenalidomide and dexamethasone (Rd).
Response rates included the following:
|Overall Response Rate||89%||77%|
|Time to reach very good partial response (VGPR)||5 months||11 months|
|MRD negative at 12 months||33%||18%|
The results in the DR group were consistent across subgroups of age, exercise status, myeloma stage, genetics, and kidney function.
Safety: During the first year of treatment, at least one adverse event (grade >3) was reported in 76% of the DR group and 64% of the Rd group. Patients in the DR group had a higher rate of grade >3 neutropenia and anemia, but similar grade > 3 infections. Discontinuations for adverse events were similar in both groups.
The authors concluded:
“In this phase 3 trial dedicated for frail patients with newly diagnosed multiple myeloma, a dexamethasone-sparing regimen combining daratumumab and lenalidomide demonstrates deep and rapid responses and a favorable safety profile.”
Based on these findings, elderly, frail patients who are newly diagnosed, as well as those who are experiencing side effects from dexamethasone, may want to discuss with their doctor whether a daratumumab and lenalidomide regimen is appropriate for them.
Additionally, this study brings to the forefront the importance of patients and caregivers having open and honest discussions with doctors regarding side effects. As ASH 2022 clearly showed, there are many treatment options for multiple myeloma patients. No one needs to suffer in silence any longer. In some cases, a change in treatment could result in fewer side effects and maybe even better results.
It is our hope that this important study will be duplicated with younger, less frail patients and all patients (and caregivers) can enjoy life with less dex.
about the author
Todd & Diane Kennedy
Todd and Diane Kennedy have been married for 33 years and raised their two sons together in Southern California. Todd was diagnosed with multiple myeloma in December 2017 and Diane has been his care partner every step of the way. In 2020 they both left their professional careers, Todd in the pharmaceutical industry and Diane in freelance marketing/writing, to focus and serve as patient advocates, research advisors, Myeloma Coaches, and support group co-leaders.