What are the initial treatment approaches for light chain myeloma?

Initial Treatment Approaches for Light Chain Myeloma

Bortezomib-based regimens are the preferred initial treatment for light chain myeloma, with VRd (bortezomib, lenalidomide, dexamethasone) being the standard of care for most patients. 1

Risk Stratification

Before initiating treatment, risk stratification is essential to guide therapy:

• Standard risk: t(11;14), t(6;14), hyperdiploidy 1
• Intermediate risk: t(4;14), cytogenetic del 13, hypodiploidy 1
• High risk: del 17p, t(14;16), t(14;20), high-risk gene expression profile 1

Initial Treatment Based on Risk and Transplant Eligibility

Transplant-Eligible Patients

• High-risk patients:

  • VRd (bortezomib, lenalidomide, dexamethasone) for 4 cycles 1
  • Consider Dara-VRd (daratumumab plus VRd) for double-hit or triple-hit myeloma 1
  • Proceed to autologous stem cell transplant (ASCT) 1
  • Continue VRd-based maintenance for at least 1 year 1

• Intermediate-risk patients:

  • CyBorD (cyclophosphamide, bortezomib, dexamethasone) for 4 cycles 1
  • Proceed to ASCT 1
  • Continue bortezomib-based maintenance for at least 1 year 1

• Standard-risk patients:

  • Rd (lenalidomide, dexamethasone) or CyBorD for 4 cycles 1
  • Proceed to ASCT 1
  • Consider lenalidomide maintenance 1

Transplant-Ineligible Patients

• For all risk categories:
  • VRd is the preferred regimen based on superior progression-free and overall survival 1, 2
  • Alternative regimens include:
    • DRd (daratumumab, lenalidomide, dexamethasone) for patients with pre-existing neuropathy 1
    • VMP (bortezomib, melphalan, prednisone) 1, 3

Special Considerations

Renal Impairment

• VCd (bortezomib, cyclophosphamide, dexamethasone) is preferred for patients with acute renal failure due to light-chain cast nephropathy 1
• Bortezomib-based regimens can be administered without dose adjustment in severe renal impairment and dialysis 1

Response Assessment

• Response criteria include normalization of involved free light chains 4
• Achieving stringent complete response (sCR) with normalization of free light chain ratio is associated with improved disease-free and overall survival 4

Treatment Duration

• For transplant-eligible patients: 4 cycles of induction therapy followed by stem cell collection and ASCT 1
• For transplant-ineligible patients: 12-18 months of therapy 5
• Maintenance therapy should be risk-adapted:
  • Standard-risk: lenalidomide maintenance 1
  • Intermediate/high-risk: bortezomib-based maintenance 1, 5

Supportive Care

• Thromboprophylaxis for patients on immunomodulatory drugs (lenalidomide):
  • Aspirin for standard-risk patients 1
  • Low-molecular weight heparin, warfarin, or direct thrombin inhibitors for high-risk patients 1
• Herpes zoster prophylaxis for all patients on proteasome inhibitors 1
• Pneumocystis jiroveci prophylaxis for patients on dexamethasone 1
• Levofloxacin during the first two cycles for all newly diagnosed patients 1

Monitoring and Follow-up

• Regular assessment of free light chain levels to monitor response 4
• Early detection of relapse is crucial, especially in high-risk patients, as relapse may be rapid and difficult to control 1

Pitfalls to Avoid

• Delaying treatment in patients with renal failure - prompt initiation of bortezomib-based therapy is essential 1
• Neglecting supportive care measures, particularly thromboprophylaxis and antimicrobial prophylaxis 1
• Using prolonged induction therapy (>4-6 cycles) in transplant-eligible patients as it may impair stem cell collection 1
• Overlooking the importance of risk stratification in treatment selection 1