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Daratumumab Enhances Myeloma Induction
Yes, daratumumab enhances myeloma induction therapy. To say this a different way, the FDA approved standard-of-care (SOC) for all newly diagnosed myeloma patients, Velcade, Revlimid and Dexamethasone (VRd), according to the research below, brings more NDMM patients to MRD status.
As a long-term MM survivor, I tend to look at MM a bit differently. I have found conventional MM wisdom to be biased. Or I should say that if you are a NDMM patient, consider these issues.
- Side Effects
- Overall Survival
- Thinking long term
Side Effects- Adding another chemotherapy regimen to a triplet adds toxicity. Nothing remarkable in this. Greater toxicity means that some patients will develop side effects that they would no develop if their induction therapy was one a triplet. A breakdown of possible side effects is listed below.
Overall Survival- If the NDMM patient does respond and does reach MRD, great. But there will be a greater percentage of NDMM patients who will not reach MRD status. The study below doesn’t mention what happens to average or below average responders but in my experience, there will be a large percentage of NDMM patients who are average and don’t reach MRD and who therefore don’t have a long overall survival.
Thinking long-term– I am in favor of having a plan B, C even D if possible. VRd is a very effective FDA approved SOC induction therapy combo. Keeping your powder dry by not taking dara gives you a terrific therapy option once you relapse post induction with VRd.
What are the pros and cons of adding daratumumab to the standard induction therapy of velcade, revlimid and dexamethasone?
Pros
- Increased Efficacy:
- Higher Response Rates: Clinical trials, such as the MAIA and CASSIOPEIA studies, have demonstrated that adding daratumumab to standard regimens increases overall response rates (ORR) and depth of response, including complete response (CR) and stringent complete response (sCR).
- Prolonged Progression-Free Survival (PFS): Patients receiving daratumumab in combination with VRd have shown longer PFS compared to those receiving VRd alone.
- Overall Survival (OS): There is evidence suggesting an improvement in overall survival rates with the addition of daratumumab, although long-term data are still being collected.
- Minimal Residual Disease (MRD) Negativity:
- Adding daratumumab increases the rates of MRD negativity, which is associated with better long-term outcomes and a lower likelihood of relapse.
- Synergistic Effect:
- Daratumumab, a monoclonal antibody targeting CD38, has a mechanism of action that complements the proteasome inhibition by bortezomib and the immunomodulatory effects of lenalidomide, enhancing the overall anti-myeloma effect.
Cons
- Increased Risk of Infections:
- Daratumumab can lead to a higher incidence of infections, including respiratory infections, due to its immunosuppressive effects.
- Infusion-Related Reactions:
- Patients often experience infusion-related reactions during daratumumab administration, particularly during the first infusion. These can include symptoms such as fever, chills, throat irritation, and dyspnea, necessitating premedication and monitoring.
- Hematologic Toxicities:
- Adding daratumumab can increase the risk of hematologic toxicities, such as neutropenia, thrombocytopenia, and anemia, which may require dose adjustments or supportive care measures.
- Cost:
- Daratumumab is a high-cost medication, and its addition to the treatment regimen significantly increases the overall cost of therapy, potentially limiting accessibility for some patients.
- Treatment Duration and Complexity:
- The inclusion of daratumumab can extend the duration and complexity of the treatment regimen, requiring more frequent hospital visits for infusions and monitoring, which can impact patient quality of life and adherence.
I have to acknowledge that I have my own biases when it comes to the overall treatment of MM. I believe that there are many, many NDMM patients who do not need all of the toxicity of either VRd induction or Dara with VRd induction. All NDMM patients who are stage 1 for example. And the NDMM patient who is frail.
man hand holding his nutritional supplemets, healthy lifestyle background.
I think evidence-based but non-conventional therapies such as
- nutrition
- supplementation and
- lifestyle therapies
should have a place in your induction therapy plan.
Are you a NDMM patient? What symptoms? What stage are you? What are your goals? If you’d like to learn more about evidence-based non-conventional therapies email me at David.PeopleBeatingCancer@gmail.com
Hang in there,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Daratumumab Treatment Advancements in Newly Diagnosed Multiple Myeloma
“A phase 3 clinical trial, PERSEUS (NCT03710603), published by The New England Journal of Medicine showed benefit in the treatment of patients with newly diagnosed (ND) multiple myeloma (MM) using monoclonal antibody daratumumab (Darzalex; Janssen Biotech, Inc and Genmab A/S) in combination with standard treatments.1 The study results found that patients who received subcutaneous administration of daratumumab were more likely to have minimal residual disease (MRD), progression-free survival (PFS), and overall better treatment outcomes…
The PERSEUS trial investigated daratumumab in combination with bortezomib (Velcade; Millennium/Takeda and Janssen Pharmaceutical Companies), lenalidomide (Revlimid; Bristol-Myers Squibb), and dexamethasone (D-VRd, Decadron; Pfizer CentreOne) to treat patients with NMDD. The primary endpoint of the study was PFS with secondary endpoints including post-consolidation MRD negativity rate, overall response rate, time to response, duration of response, and overall survival.1…
The randomized clinical trial involved 700 people with NDMM who were eligible for stem cell transplantation across 14 countries in Europe and Australia. Patients were randomly assigned to receive standard regimens—induction therapy with VRd, consolidation therapy with VRd, maintenance therapy with lenalidomide, and stem cell transplant—with or without subcutaneous daratumumab. Patients who received daratumumab received it as part of induction, consolidation, and maintenance therapies. The treatment outcomes were measured for a median of approximately 4 years.3
The findings showed that daratumumab in combination with VRd was overall more effective than standard treatments with higher rates of complete response and MRD negativity, with 84% of patients exhibiting PFS at 4 years (hazard ratio = .42; 95% confidence interval, .30 to .59; P<.001). Additionally, the number of patients with a complete response to treatment was greater than the number who did not receive daratumumab (87.9% vs. 70.1%, P<.001), as well as MRD-negativity status (75.2% vs. 47.5%, P<.001).3,4…