What is the next best step in management for a patient with multiple myeloma and a 17p deletion who has achieved a partial response to bortezomib, lenalidomide (Revlimid), and dexamethasone (Decadron)?

Proceed to Autologous Stem Cell Transplantation (ASCT) Followed by Lenalidomide Maintenance

For this 48-year-old patient with multiple myeloma harboring a high-risk 17p deletion who has achieved a partial response to bortezomib, lenalidomide, and dexamethasone (VRd), the next step is to proceed with high-dose melphalan (200 mg/m²) and autologous stem cell transplantation, followed by lenalidomide maintenance therapy. 1, 2

Rationale for ASCT in This Clinical Context

High-Risk Disease Requires Aggressive Consolidation

• The presence of 17p deletion classifies this patient as high-risk multiple myeloma, which historically portends shorter progression-free survival (PFS) after transplantation 1, 3, 4
• The patient has achieved a partial response (PR) to VRd induction—this is an appropriate depth of response to proceed to transplant, as responses typically deepen significantly post-ASCT 1, 2
• In the IFM 2008 trial, VGPR rates improved from 58% post-induction to 70% post-transplant and reached 87% after consolidation therapy 1

Evidence Supporting ASCT After VRd Induction

• The SWOG S0777 trial demonstrated that VRd induction followed by ASCT resulted in superior outcomes: median PFS of 43 months versus 30 months with lenalidomide-dexamethasone alone, and median overall survival (OS) of 75 months versus 64 months 1
• A large cohort study (n=1,000) showed that VRd induction followed by ASCT achieved VGPR or better in 89.9% of patients, with median PFS of 65 months for the entire cohort 5
• Even in high-risk patients, this approach yielded a median OS of 78.2 months and 5-year OS of 57% 5

Specific Treatment Algorithm

Step 1: Proceed to ASCT Without Delay

• Administer high-dose melphalan 200 mg/m² followed by autologous stem cell infusion 2, 6
• Transplant should occur within 6-12 months of diagnosis in eligible patients to maximize benefit 2
• Do not delay transplant once adequate response (PR or better) is achieved, as prolonged lenalidomide exposure may impair stem cell mobilization 1, 2

Step 2: Consider Consolidation Therapy

• After ASCT, consider 2 cycles of VRd consolidation to further deepen response 1, 2
• The IFM 2008 trial demonstrated that consolidation improved VGPR rates from 70% post-transplant to 87% after consolidation 1

Step 3: Initiate Maintenance Therapy

• Begin lenalidomide maintenance therapy after transplant and any consolidation, continuing until disease progression 1, 2
• For high-risk patients with 17p deletion, consider bortezomib plus lenalidomide maintenance rather than lenalidomide alone 1, 4
• One study specifically showed that adding bortezomib to long-term therapy in patients with p53 deletion (17p deletion) improved both PFS and OS 1

Why Other Options Are Not Appropriate

Do Not Continue Current Regimen Alone

• Simply continuing VRd without ASCT would deprive this patient of the proven survival benefit of transplantation (median OS 75 months with ASCT vs 64 months without) 1
• The patient has already received 3 cycles of bortezomib followed by lenalidomide-dexamethasone—this is sufficient induction therapy 1, 2

Do Not Switch to Melphalan-Based Triplet Without ASCT

• Bortezomib-melphalan-dexamethasone (or melphalan-prednisone-bortezomib) is reserved for transplant-ineligible patients 1, 7
• This 48-year-old patient is clearly transplant-eligible based on age and performance status (able to climb stairs, though with dyspnea)

Allogeneic Transplant Is Not Standard of Care

• Allogeneic hematopoietic cell transplantation is not a standard treatment option for multiple myeloma outside of clinical trials 1
• While this patient has high-risk disease, the current standard approach is ASCT followed by maintenance, not allogeneic transplant

Critical Considerations for 17p Deletion

Enhanced Maintenance Strategy

• The 17p deletion confers high-risk status and requires more aggressive maintenance 1, 4
• Consider bortezomib-based maintenance in addition to lenalidomide, as this has shown OS improvement specifically in patients with p53 deletion 1
• Continue maintenance therapy until progression, as high-risk patients may experience rapid and difficult-to-control relapse if not treated immediately 1

Monitoring Strategy

• Perform myeloma workup every 3-6 months during maintenance, including serum protein electrophoresis (SPEP), immunofixation, free light chains, and complete blood count 8
• Monitor for peripheral neuropathy given prior bortezomib exposure—consider dose modifications if grade ≥2 neuropathy develops 1, 6

Common Pitfalls to Avoid

• Do not delay transplant waiting for a deeper response—partial response is sufficient to proceed, and responses deepen post-ASCT 1, 2
• Do not omit maintenance therapy in this high-risk patient—maintenance is critical for prolonging PFS and OS in 17p deletion patients 1, 4
• Do not use lenalidomide maintenance alone in high-risk disease—consider adding bortezomib to the maintenance regimen 1, 4
• Do not pursue allogeneic transplant outside of a clinical trial—this is not standard of care 1