Optimizing the lenalidomide, bortezomib, and dexamethasone regimen to enhance patient experience while maintaining treatment efficacy
For the thousands of patients diagnosed with multiple myeloma each year, the combination of lenalidomide, bortezomib, and dexamethasone (known as RVD or VRd) has become a cornerstone of treatment. This powerful three-drug regimen has helped drive impressive gains in survival, with recent real-world studies showing median survival has nearly doubled from 2.4 to 4.5 years since the early 2000s 9 . Yet behind these encouraging statistics lies a complex treatment experience fraught with time-consuming clinic visits, significant financial burdens, and demanding side effects.
"Despite the enormous advances in the treatment of MM in the last decades, MM remains incurable, therefore using the best treatments available at each stage of the disease is of great importance" 4 .
Today, researchers and clinicians are tackling a critical challenge: how to make this life-extending treatment more efficient—reducing costs, decreasing clinic time, and maintaining safety—so patients can focus more on living their lives and less on managing their treatment.
Traditional IV administration required lengthy clinic visits, disrupting patients' daily lives and reducing quality of life.
High treatment costs create significant financial burdens for patients and healthcare systems alike.
Treatment-related toxicities like peripheral neuropathy can limit therapy duration and effectiveness.
The most significant breakthrough in treatment efficiency has come from a simple switch in how bortezomib is administered. Traditional intravenous (IV) delivery required lengthy clinic visits for infusion, but the subcutaneous (SC) formulation has changed the game:
Traditional IV administration time
Subcutaneous administration time 9
This shift isn't just about convenience—it has meaningful clinical benefits. Research directly comparing administration methods found that subcutaneous delivery significantly reduces common side effects including peripheral neuropathy, infections, and digestive problems, all without compromising the drug's effectiveness against myeloma cells 9 .
| Parameter | Subcutaneous | Intravenous |
|---|---|---|
| Administration time | 2-5 minutes | 1-3 hours |
| Peripheral neuropathy risk | Lower | Higher |
| Infection risk | Reduced | More common |
| Digestive side effects | Less severe | More frequent |
| Effectiveness against myeloma | Maintained | Maintained |
Visualization: Comparison of treatment administration times and side effect profiles between SC and IV bortezomib
While the switch to subcutaneous bortezomib addresses administration efficiency, comprehensive clinic time reduction requires broader strategies:
Grouping appointments, tests, and consultations to minimize separate visits
Using telehealth for routine follow-ups when appropriate
Once bortezomib treatment moves to maintenance phases, spacing out doses reduces visit frequency
Teaching self-administration of certain supportive medications when safe and appropriate
For patients like Maria, a 68-year-old grandmother recently diagnosed with myeloma, these efficiency gains have been life-changing.
"Before we switched to the subcutaneous injections, treatment days meant spending half my day at the clinic—driving, parking, waiting, then the long infusion. Now I'm in and out in under an hour. That might not sound like much, but when you're juggling treatment with family and trying to maintain some normalcy, those hours matter."
The cumulative impact of these strategies can be substantial. When the IMROZ clinical trial added isatuximab to VRd, they developed precisely scheduled treatment calendars that optimized timing across induction, consolidation, and maintenance phases 9 . Such structured approaches minimize unnecessary clinic time while maintaining treatment efficacy.
The financial burden of myeloma treatment extends far beyond drug prices, encompassing:
Drugs, administration supplies, clinic overhead
Patient transportation, time off work for both patients and caregivers
Managing side effects, additional supportive medications
Recent analyses have revealed surprising opportunities for savings. A 2025 study found that the subcutaneous formulation of daratumumab with VRd (D-VRd) cost approximately $27,000 less per patient in the first two years of treatment compared to similar quadruplet regimens 7 . These savings came from both reduced drug acquisition costs and significantly less administration time.
| Regimen | Total Cost (Patient <75 years) | Total Cost (Patient ≥75 years) | Cumulative Administration Time |
|---|---|---|---|
| D-VRd (daratumumab) | $818,675 | $818,440 | ~58 hours less |
| Isa-VRd (isatuximab) | $846,388 | $846,320 | Baseline |
Reducing costs isn't just about saving money—it's about ensuring patients can continue effective treatment without financial toxicity leading to interruptions or dose reductions. Research shows that maintaining planned treatment intensity correlates with better outcomes, making cost-effective strategies essential for both individual patients and healthcare systems.
As one economic evaluation concluded: "The 2019 decision to universally fund VRd for newly diagnosed multiple myeloma did not result in a cost-effective allocation of healthcare resources when judged against traditional thresholds" 3 , highlighting the ongoing need for efficiency improvements in real-world practice.
A common concern when streamlining treatments is whether safety might be compromised. The evidence suggests otherwise:
The Connect® MM Registry showed that RVd induction actually improved renal function in patients with all severities of renal impairment at baseline, with benefits observed at 3, 6, and 12 months 1 .
The IMROZ trial demonstrated that frail patients derived similar benefits from VRd-based regimens as fitter patients, with appropriate support and monitoring 9 .
Research confirms that reduced-dose dexamethasone schedules for older patients maintain effectiveness while minimizing side effects 7 .
Efficiency improvements often enhance safety rather than compromise it. For example:
The key is personalized treatment planning—using frailty assessments, comorbidity evaluations, and regular toxicity monitoring to tailor treatment intensity to individual patients .
| Safety Concern | Prevention Strategy | Monitoring Approach |
|---|---|---|
| Peripheral neuropathy | Use subcutaneous bortezomib; avoid consecutive day dosing | Regular neurological assessments; patient symptom logs |
| Infection risk | Antibiotic prophylaxis when neutropenic; immunoglobulin replacement if indicated | Regular blood counts; prompt fever evaluation |
| Venous thromboembolism | Thromboprophylaxis with aspirin or anticoagulants based on risk | Regular risk assessment; patient education on symptoms |
| Renal toxicity | Dose adjustment for lenalidomide based on creatinine clearance | Regular renal function testing; hydration management |
The evolution of RVD efficiency continues with several promising developments:
Studies exploring even longer intervals between maintenance doses to further reduce clinic visits while maintaining efficacy.
Using genetic markers and minimal residual disease (MRD) status to guide treatment duration, potentially allowing safe discontinuation in some patients 6 .
New four-drug regimens that build on the RVD backbone while offering more convenient administration schedules.
Remote monitoring platforms that reduce the need for in-person visits while maintaining close patient oversight.
As research continues, the focus is shifting toward precision efficiency—right-sizing treatment intensity and frequency based on individual patient factors, disease characteristics, and treatment response markers like MRD status.
The optimization of RVD therapy for multiple myeloma represents a quiet revolution in cancer care—one that prioritizes not just survival but quality of life during treatment. By implementing subcutaneous administration, coordinating care to minimize clinic time, managing costs through strategic regimen selection, and maintaining safety through personalized dosing, clinicians are transforming the treatment experience.
As the evidence shows, efficiency and excellence in myeloma care aren't opposing goals—they're complementary. When treatments become more manageable, patients are more likely to receive the full benefit of modern medicine's advances. The future of myeloma care isn't just about developing more powerful drugs; it's about delivering current treatments in smarter, more patient-friendly ways that honor both the science of oncology and the art of healing.
"Getting my life back doesn't just mean living longer—it means having the time and energy to enjoy the life I'm fighting for."
Through continued refinement of regimens like RVD, that goal becomes increasingly attainable for the thousands living with myeloma today.