What is the next best step for a patient with multiple myeloma who has achieved a partial response to initial therapy with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone?

High-Dose Melphalan with Autologous Stem Cell Transplantation

For this transplant-eligible patient with newly diagnosed multiple myeloma and del(17p) who has achieved a partial response to VRd induction, you should proceed immediately to high-dose melphalan (200 mg/m²) followed by autologous stem cell rescue (Option D).

Rationale for Immediate Transplantation

The standard treatment pathway for transplant-eligible patients after achieving at least a partial response to VRd induction is to proceed directly to high-dose melphalan with autologous stem cell transplantation. 1 This approach is supported by multiple lines of evidence:

• The IFM 2008 trial demonstrated that response deepens significantly after transplantation, with VGPR rates improving from 58% post-induction to 70% post-transplant and ultimately 87% after consolidation therapy 2, 1

• The NCCN guidelines recommend that transplant should occur within 6-12 months of diagnosis in eligible patients to maximize benefit 1

• Prolonged exposure to lenalidomide may impair stem cell mobilization, making it critical not to delay transplantation once adequate response is achieved 1

Why Not the Other Options

Continuing VRd (Option A) is inappropriate because the patient has already completed the standard 3-4 cycles of induction therapy and achieved a partial response, which is sufficient to proceed to transplant 2, 3. Continuing induction therapy delays the proven benefits of consolidation with high-dose therapy.

Switching to bortezomib-melphalan-dexamethasone (Option B) is incorrect because this regimen is reserved for transplant-ineligible patients, not as a bridge to transplantation 2, 4. The patient is clearly transplant-eligible based on the clinical presentation.

Beginning maintenance lenalidomide alone (Option C) is premature because maintenance therapy should only be initiated after transplantation (and any consolidation therapy), not in place of it 2, 1, 3. The IFM 2008 trial specifically showed that lenalidomide maintenance follows transplant and consolidation 2.

Allogeneic transplantation (Option E) is not indicated as first-line therapy for multiple myeloma, even with high-risk features like del(17p) 2. While del(17p) confers high-risk status, the current standard remains autologous transplantation followed by maintenance therapy 2, 5.

Special Consideration for Del(17p)

This patient's del(17p) cytogenetic abnormality places them in the high-risk category 2, 5. However, this does not change the immediate next step:

• Bortezomib-based regimens (like the VRd this patient received) partially overcome the adverse prognosis of del(17p) 5

• High-risk patients should still proceed to autologous transplantation after induction 2, 3, 5

• The high-risk status will influence post-transplant management, where bortezomib-based maintenance (rather than lenalidomide alone) may be preferred 2, 3, 5

Complete Treatment Sequence

The optimal pathway for this patient is:

1. Immediate high-dose melphalan (200 mg/m²) with autologous stem cell rescue 1, 3

2. Consider 2 cycles of VRd consolidation post-transplant to further deepen response (VGPR rates reached 87% after consolidation in IFM 2008) 2, 1

3. Initiate maintenance therapy after transplant and consolidation, continuing until disease progression 2, 1, 3. Given the del(17p) high-risk feature, bortezomib-based maintenance may be preferred over lenalidomide alone 2, 3, 5

Critical Timing

Do not delay transplantation. The patient has achieved the necessary response threshold (partial response), has no contraindications to transplant based on the clinical presentation, and should proceed immediately to maximize the depth and duration of response 1. Peripheral blood progenitor cells should be used as the stem cell source 3.