Recently Diagnosed or Relapsed? Stop Looking For a Miracle Cure, and Use Evidence-Based Therapies To Enhance Your Treatment and Prolong Your Remission
Multiple Myeloma an incurable disease, but I have spent the last 25 years in remission using a blend of conventional oncology and evidence-based nutrition, supplementation, and lifestyle therapies from peer-reviewed studies that your oncologist probably hasn't told you about.
Click the orange button to the right to learn more about what you can start doing today.
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Better Myeloma Induction Therapy?
A better myeloma induction therapy? Better than what? Better in what way? Similar overall response yet fewer side effects, aka less toxicity.
Keep in mind that the clinical trial discussed below is a stage 2 study, meaning, the study is far from reaching your oncologist’s office. But the important thing is that this is the first MM drug trial that I know if that focuses primarily on side effects or quality of life.
During the video discussion below, Dr. Yee mentions “older, ASCT-ineligible MM patients” repeatedly. However, I think that ALL newly diagnosed MM patients should consider an induction therapy that brings similar efficacy with lower toxicity to the table.
AFT-41 trial: daratumumab, lenalidomide, ixazomib, and dexamethasone in transplant-ineligible NDMM
Since we’re talking about the efficacy of induction therapy, I need to promote Prehabilitation, which is simply getting in shape for chemo with nutrition, exercise, and supplementation.
Are you a newly diagnosed MM patient? Email me at David.PeopleBeatingCancer@gmail.com with your questions about both conventional and non-conventional MM therapies.
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Multiple Myeloma: Novel Quad Regimen Eases Toxicity
A quadruplet regimen for treating transplant-ineligible, newly diagnosed multiple myeloma (MM), combining the oral drug ixazomib with daratumumab, lower-dose lenalidomide, and dexamethasone (Dara-RId), shows notable improvements in tolerability, with important reductions in neutropenia and peripheral neuropathy vs other quadruplet regimens, new research shows.
“Dara-RId offers a regimen that has the efficacy of a four-drug combination with the convenience of oral ixazomib, minimizing the risk of peripheral neuropathy for older, transplant ineligible newly diagnosed MM…”
Patients with newly diagnosed MM are often not eligible for transplant when age or frailty reduce their tolerability to treatment toxicities, and while recent quadruple therapy regimens have shown encouraging improvements in progression-free survival, some patients still do not respond.
To explore a potentially improved quadruplet treatment regimen, Yee and his colleagues conducted the multicenter, phase 2 Alliance Foundation Trial 41, involving some key modifications from previous regimens, including the reduction of the dose of lenalidomide from 25 mg to 15 mg and replacement of the proteasome inhibitor bortezomib with oral ixazomib.
The inclusion of ixazomib offers several key advantages, including the oral formulation immediately being more patient-friendly — patients do not have to come into clinic as often to receive this therapy, “and, being an oral medication, it also allows for extended therapy,” Yee explained.
In addition, ixazomib has a significantly reduced risk for peripheral neuropathy compared with the commonly used bortezomib.
“This is particularly meaningful for older, frailer patients, who may be more prone to falls,” he emphasized…
All patients received induction with 12 cycles of the regimen: subcutaneous daratumumab 1800 mg and oral lenalidomide 15 mg on days 1 through 21; oral ixazomib 4 mg on days 1, 8, 15; and dexamethasone weekly. Each cycle was 28 days.
Following the 12 cycles, patients received maintenance with either Dara-RId or lenalidomide, based on prior randomization, for up to 2 years, with lenalidomide reduced to 10 mg and ixazomib reduced to 3 mg during the maintenance period.
The patients had a median age of 74, with nearly half (45.6%) aged 75 or older; 59% were female; and 83.5% were White. Approximately 40% of patients were considered to be frail.
At baseline,
- 41.8% of patients had International Staging System (ISS) stage I cancer,
- 35.4% had stage II,
- and 22.8% had stage III,
- with high-risk features in 37% by stage III and/or high-risk FISH.
In terms of outcomes during induction, the objective response rate was 92.4% and the partial response rate was 22.8%. Very good partial response occurred in 46.8%, complete response in 15.2%, and stringent complete response in 7.6%.
After 12 cycles of Dara-RId, the rate of progression-free survival was 92% and the overall survival rate was 93.6%.
Similar outcomes were observed between standard-risk and high-risk patients, as defined by the trial.
Older Age Key to Worse Outcomes?
Of note, the 12-month progression-free survival rate was 95.4% in those who were not considered frail, based on their simplified frailty score, compared with 87.2% in those who were frail.
Likewise, the progression-free survival rate was higher among patients who were under 80 and nonfrail (95.4%) compared with those who were over 80 (all frail, by definition; 72.7%).
“Frail patients tend to have early progression events, though age over 80 may be a more important factor with induction outcomes,” Yee said.
Adverse events with the regimen were generally consistent with those observed with other quadruplet therapies, with grade 3 or higher neutropenia occurring in 16.5% of patients, infections in 11.4%, and anemia in 10.1%.
Furthermore, there were no reports of grade 3 or higher neuropathy (grade 1, 15%; grade 2, 14%).
Of note, no treatment-related deaths were reported, with 61 patients going on to maintenance therapy and seven patients discontinuing treatment for adverse events during induction.
Improvements vs Other Quadruplet Trials
As expected, frail patients tended to have more dose reductions of lenalidomide and ixazomib vs nonfrail patients; however, the overall tolerability was encouraging, Yee said.
“It should be emphasized that there is improved tolerability compared with what we see with other regimens,” he noted.
“In particular, the rate of grade 3 neutropenia in our study was about 17%, which is significantly lower than in the other regimens that we have heard about, and I think this is probably due to the lower dose of lenalidomide used in the study. Moreover, there was a significantly reduced rate of peripheral neuropathy with the use of ixazomib, including all-grade neuropathy and in particular, grade 3 or higher neuropathy…”
Specifically, rates of grade 3 or higher neutropenia (16.5% in the current study) were 44.2% and 50% in the Dara-VRd CEPHEUS and Dara-Rd MAIA quadruplet trials, respectively.
Peripheral neuropathy of any grade or of grade 3 or above, at 29% and 0%, respectively, in the current trial, were comparatively 61.9% and 11.2% in the CEPHEUS trial…
Yee noted that findings represent early preliminary data. Further study outcomes from the maintenance arm, and the depth of responses by minimal residual disease, are pending.
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