What is the initial treatment approach for a patient with myeloma, considering factors such as disease stage, age, and overall health?

Treatment for Multiple Myeloma

For transplant-eligible patients (typically <65-70 years, good performance status), initiate triplet induction therapy with bortezomib, lenalidomide, and dexamethasone (VRd), followed by high-dose melphalan (200 mg/m²) with autologous stem cell transplantation, then lenalidomide maintenance until progression. 1, 2

Initial Assessment: Determining Transplant Eligibility

Transplant eligibility is the critical first decision point that determines your entire treatment pathway 1:

• Transplant-eligible criteria: Age <65-70 years, good performance status, absence of significant comorbidities, adequate organ function 1
• Assess frailty status using geriatric assessment factors including functional status (independence in activities of daily living), comorbidities, which predict treatment toxicity and survival 1
• Obtain cytogenetics via FISH to identify high-risk features: del(17p), t(4;14), t(14;16) - these affect prognosis but not initial treatment selection for standard regimens 1

Transplant-Eligible Patients: The Standard Pathway

Induction Therapy (4-6 cycles)

Bortezomib, lenalidomide, and dexamethasone (VRd) is the preferred induction regimen 1, 2, 3:

• Bortezomib: 1.3 mg/m² subcutaneously (not IV - reduces neuropathy risk) on days 1,4,8,11 of each 21-day cycle 2, 3, 4
• Lenalidomide: 25 mg orally days 1-14 of each 21-day cycle 2
• Dexamethasone: 40 mg weekly (or 20 mg weekly if age >75 years) 2

Critical point: Use subcutaneous bortezomib administration rather than intravenous to significantly reduce peripheral neuropathy 3, 4. Avoid melphalan-containing regimens (melphalan-prednisone-thalidomide, bortezomib-melphalan-prednisone) in transplant-eligible patients as melphalan damages stem cells 2.

Stem Cell Collection and Transplantation

• Collect peripheral blood stem cells after induction, not bone marrow 1
• High-dose melphalan 200 mg/m² IV is the standard conditioning regimen before autologous transplantation 1, 4
• Timing: Proceed to transplant after achieving best response to induction (typically 4-6 cycles) 5

Maintenance Therapy

Lenalidomide maintenance should be continued until disease progression after transplant 1, 2, 3:

• Provides median progression-free survival of 41 months 3, 5
• Standard dosing: 10-15 mg daily, days 1-21 of 28-day cycles 2

Transplant-Ineligible Patients: Age-Adapted Approach

For Fit Elderly Patients (Age >65-70 years)

Triplet therapy with VRd or daratumumab-bortezomib-melphalan-prednisone (D-VMP) should be considered 1, 2:

• VRd regimen: Same as above but continue for 8-12 cycles, then lenalidomide maintenance until progression 1, 2
• D-VMP alternative: Daratumumab plus bortezomib, melphalan, prednisone for select patients 1

At minimum, use a doublet regimen with a novel agent (immunomodulatory drug or proteasome inhibitor) plus steroid 1:

• Lenalidomide-dexamethasone continuous therapy is superior to fixed-duration melphalan-prednisone-thalidomide 1
• Melphalan-prednisone alone is obsolete and should not be used 1

Critical Dose Modifications for Elderly/Frail Patients

Reduce dexamethasone to 20 mg once weekly for patients >75 years - standard dosing (40 mg weekly) significantly increases toxicity and mortality in this age group 2. For frail patients, start dexamethasone at 8-20 mg weekly with subsequent titration 2.

Frailty assessment predicts treatment toxicity: Patients classified as frail have higher rates of treatment discontinuation and worse outcomes 1. Consider less intensive regimens or further dose reductions in frail patients 2.

Essential Supportive Care (All Patients)

Mandatory interventions that reduce morbidity 2, 3, 6:

• Herpes zoster prophylaxis: Acyclovir or valacyclovir for all patients receiving bortezomib or monoclonal antibodies 2, 3
• Thromboprophylaxis: Full-dose aspirin (81-325 mg daily) for lenalidomide-based regimens 2, 3
• Bisphosphonates: Zoledronic acid or pamidronate to reduce skeletal-related events in stage III or bone disease 1, 6

Asymptomatic/Smoldering Myeloma

Do not treat asymptomatic myeloma - immediate treatment is not recommended 1, 6. Monitor at 3-6 month intervals with laboratory tests and imaging 6.

Common Pitfalls to Avoid

• Never use standard dexamethasone dosing (40 mg weekly) in patients >75 years - this significantly increases mortality 2
• Avoid melphalan in potentially transplant-eligible patients - it is stem cell toxic and precludes future transplant 2
• Do not use multiagent chemotherapy regimens in elderly patients - they are inferior to novel agent combinations 1
• Do not delay treatment in symptomatic patients while attempting conservative measures, especially with renal involvement 6

Response Monitoring

Assess response after every 2 cycles using 2, 3, 6:

• Serum protein electrophoresis and immunofixation
• Serum free light chains
• Monitor for peripheral neuropathy closely with bortezomib therapy 2

Complete response requires: <5% plasma cells in bone marrow, negative immunofixation, and resolution of soft tissue plasmacytomas 3, 4.