What is the standard treatment protocol for multiple myeloma?

Standard Treatment Protocol for Multiple Myeloma

The standard treatment protocol for multiple myeloma is based on transplant eligibility, with transplant-eligible patients receiving triplet induction therapy with bortezomib, lenalidomide, and dexamethasone (VRd) followed by autologous stem cell transplantation (ASCT) and maintenance therapy, while transplant-ineligible patients receive either VRd or bortezomib-melphalan-prednisone (VMP). 1, 2

Initial Assessment and Diagnosis

• Treatment should be initiated in patients with active myeloma fulfilling the CRAB criteria: hypercalcemia (>11.0 mg/dl), renal insufficiency (creatinine >2.0 mg/ml), anemia (Hb <10 g/dl), or active bone lesions 3
• Risk stratification is essential using the International Staging System and cytogenetic analysis to identify high-risk features such as del(17p), t(4;14), t(14;16), t(14;20), or gain 1q 3, 2
• Whole-body low-dose CT is preferred over conventional skeletal survey for bone assessment 1

Treatment Approach Based on Transplant Eligibility

Transplant-Eligible Patients (<65 years or fit patients)

• Induction Therapy:

  • Standard regimen: Bortezomib, lenalidomide, and dexamethasone (VRd) for 3-4 cycles 1, 2
  • Alternative triplet regimens including bortezomib and dexamethasone plus another agent: VTD (bortezomib, thalidomide, dexamethasone), VCD (bortezomib, cyclophosphamide, dexamethasone), or PAD (bortezomib, doxorubicin, dexamethasone) 3
  • For high-risk patients, daratumumab-VRd (Dara-VRd) is an alternative to VRd 2

• Stem Cell Collection and Transplantation:

  • Peripheral blood progenitor cells are preferred over bone marrow as the source of stem cells 3
  • High-dose melphalan (200 mg/m² IV) is the standard preparative regimen before ASCT 3
  • Three to four courses of induction therapy are recommended before proceeding to stem cell collection 3

• Post-Transplant Therapy:

  • Maintenance therapy with lenalidomide should be continued until disease progression for standard-risk patients 1, 2
  • For high-risk patients, bortezomib-based maintenance or combination maintenance with bortezomib plus lenalidomide is recommended 2

Transplant-Ineligible Patients (Elderly or unfit)

• First-line Treatment Options:

  • Bortezomib-melphalan-prednisone (VMP) or melphalan-prednisone-thalidomide (MPT) are standards of care in Europe 3
  • VRd for approximately 8-12 cycles followed by lenalidomide maintenance 2
  • Daratumumab-lenalidomide-dexamethasone (DRd) is an alternative regimen with significant improvement in progression-free survival compared to lenalidomide-dexamethasone 4, 2
  • Bendamustine plus prednisone is approved for patients with clinical neuropathy at diagnosis that precludes the use of thalidomide or bortezomib 3

• Dosing Considerations:

  • Bortezomib is administered twice weekly in cycles 1-4 (days 1,4,8,11,22,25,29,32) and once weekly in cycles 5-9 (days 1,8,22,29) when combined with melphalan and prednisone 5
  • At least 72 hours should elapse between consecutive doses of bortezomib 5

Special Considerations

• High-Risk Disease Management:

  • Patients with high-risk cytogenetic features (del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation) require more intensive approaches 2
  • Double-hit (two high-risk factors) or triple-hit (three or more high-risk factors) myeloma patients have particularly poor outcomes and may benefit from more aggressive therapy 2

• Supportive Care:

  • Thromboprophylaxis is essential for patients on immunomodulatory drugs 1
  • Bisphosphonates should be administered to reduce skeletal-related events 3, 6
  • Dose modifications may be necessary for peripheral neuropathy, which is common with bortezomib therapy 5

Treatment Response Assessment

• Response should be assessed with each treatment cycle using serum and urine electrophoresis 1
• Complete response requires <5% plasma cells in bone marrow and negative immunofixation 1

Relapsed Disease Management

• Most patients require triplet regimens at relapse, with the choice varying with each successive relapse 2
• Prior therapies should be considered when selecting treatment at first relapse 3

Common Pitfalls and Caveats

• Asymptomatic (smoldering) myeloma should not receive immediate treatment 3
• Allogeneic stem cell transplantation should only be considered in the context of a clinical trial and only in patients with good response before transplant 3
• Peripheral neuropathy is a significant concern with bortezomib therapy and requires careful monitoring and dose adjustments as needed 5
• While VRd is the standard induction regimen, the ENDURANCE trial showed that carfilzomib-based regimens (KRd) did not improve progression-free survival compared to VRd and had more toxicity 7