What is the comparison of a quadruplet therapy of DVRd versus a triplet therapy of VRd for newly diagnosed myeloma patients undergoing induction therapy?
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Quad vs Triplet Induction for Myeloma?
Quad vs. Triplet induction for myeloma patients is a decision that most newly diagnosed MM must make. If you are an NDMM patient, you may be considering a triplet or quadruplet chemo cocktail for your induction therapy plan.
What are the pros and cons of one versus the other?
ChatGPT said:
The comparison of DVRd (Daratumumab + Bortezomib + Lenalidomide + Dexamethasone) vs. VRd (Bortezomib + Lenalidomide + Dexamethasone) for newly diagnosed multiple myeloma (NDMM) has been studied in clinical trials, with DVRd showing improved outcomes over VRd. Below is a detailed comparison:
π¬ Key Clinical Trial: GRIFFIN Study (Phase 2)
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Design: Randomized, open-label trial.
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Population: Transplant-eligible NDMM patients.
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Arms:
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DVRd (quadruplet)
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VRd (triplet)
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π Efficacy Comparison
| Outcome | DVRd (Quadruplet) | VRd (Triplet) | P-Value / Significance |
|---|---|---|---|
| sCR (Stringent Complete Response) | 63.6% | 47.4% | P = 0.0253 |
| MRD Negativity (10β»β΅ sensitivity) | 51.0% | 20.4% | P < 0.0001 |
| Overall Response Rate (ORR) | ~99% | ~91% | Statistically significant |
| Progression-Free Survival (PFS) | Longer, trend favoring DVRd (but trial not powered for OS/PFS) | Shorter | Descriptive only |
| Time to response | Faster in DVRd group | Slower | Notable clinically |
π‘οΈ Safety and Toxicity
| Adverse Events | DVRd | VRd |
|---|---|---|
| Neutropenia | β Higher (Grade 3/4 ~60%) | Lower (Grade 3/4 ~40%) |
| Infections | β Higher in DVRd, mostly manageable | Lower |
| Peripheral Neuropathy | Comparable | Comparable |
| Infusion Reactions | Seen with daratumumab; mostly Grade 1-2 | Not applicable |
Despite the increased toxicity, most side effects were manageable with supportive care.
π‘ Clinical Implications
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DVRd is superior in achieving deeper responses (sCR and MRD negativity), which correlates with better long-term outcomes.
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Standard of Care Shift: DVRd is increasingly favored for transplant-eligible NDMM patients.
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Guidelines:
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NCCN, EMN, and IMWG now recommend DVRd as a preferred regimen for eligible patients.
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For transplant-ineligible patients, D-Rd or D-VMP may be considered based on comorbidities.
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π Summary
| Factor | DVRd | VRd |
|---|---|---|
| Depth of Response | β Better | β Inferior |
| MRD Negativity | β Higher | β Lower |
| Toxicity | β οΈ More (especially neutropenia, infections) | β Lower |
| Use in Guidelines | β Increasingly preferred | β Still acceptable, esp. in resource-limited settings |
I am a long-term MM survivor. I have learned the importance of combining both conventional and non-conventional therapies. Nothing mentioned above comes from the non-conventional, aka non-FDA-approved world. If you have not yet begun induction therapy, please consider prehabilitation with anti-angiogenic nutrition, supplementation, moderate exercise, and other lifestyle therapies. By getting in shape to undergo treatment, you will enhance your therapy while reducing your risk of side effects, according to research.
Good luck,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Consensus Guidelines and Recommendations for The CD38 Monoclonal Antibody-based Quadruplet Therapy and Management in Clinical Practice for Newly Diagnosed Multiple Myeloma: From the Pan-Pacific Multiple Myeloma Working Group
Abstract
The therapeutic outcomes of clinical trials for incorporating anti-CD38 monoclonal antibodies (including isatuximab and daratumumab) into the bortezomib/lenalidomide/dexamethasone (VRd) triplet therapy backbone as the first-line treatment for newly diagnosed multiple myeloma (NDMM) have demonstrated significant improved efficacies.
From a safety perspective, the addition of anti-CD38 monoclonal antibodies into the triplet therapies did not raise additional safety concerns. Based on the promising results, the National Comprehensive Cancer Network (NCCN) Guidelines Version 1.2025 had updated the quadruplet therapy, incorporating anti-CD38 monoclonal antibodies with VRd-based therapies as the primary therapy for both transplantation-eligible and transplantation-ineligible NDMM patients.
Thus, a panel of experts in hematology and oncology with extensive experience in the treatment of NDMM was convened in 2024 to develop consensus recommendations based on recent evidence from pivotal clinical trials and real-world practices, providing clear guidance for optimizing treatment strategies in both transplantation-eligible and transplantation-ineligible patients.
The main topics identified for discussion and recommendation were:
- (i) the benefits and indications for quadruplet therapy for NDMM;
- (ii) the optimization of quadruplet therapy strategies;
- (iii) the management and monitoring of potential adverse events for quadruplet therapy, and
- (iv) the impact of quadruplet regimens on tandem stem cell transplantation and maintenance treatment. Recommendations were then presented to the entire panel for further discussion and amendment before voting.
This manuscript presents the recommendations developed, including ο¬ndings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation…
However, despite its widespread use (of triplet therapy), limitations persist in terms of efficacy and tolerability. The SWOG S0777 trial, a key study evaluating the VRd regimen, reported a median progression-free survival (PFS) of 41 months, with 23% of patients discontinuing treatment due to AEs.1,2 Moreover, 33% of patients experienced grade 3 or higher peripheral neuropathy, significantly impacting their quality of life and ability to continue long-term treatment…
These challenges highlight the need for optimizing first-line treatment strategies to improve patient outcomes without compromising tolerability.
The concept of MRD negativity has gained prominence as a critical endpoint in multiple myeloma treatment, with accumulating evidence suggesting that it is a reliable predictor of long-term outcomes, including PFS and OS.6,7
The ability to consistently achieve this outcome has become a central goal of modern myeloma therapy, particularly in the context of optimizing long-term disease management and reducing relapse rates…
conclusion
The results of IMROZ, BENEFIT, and GMMG-CONCEPT, along with those of the CEPHEUS and ALCYONE trials, highlight the critical role of the quadruplet regimen containing anti-CD38 in optimizing outcomes for NDMM patients who are ineligible for transplant…”
Quad vs. Triplet induction for myeloma Quad vs. Triplet induction for myeloma