What are the treatment options for multiple myeloma and leukemia?

Treatment Options for Multiple Myeloma and Leukemia

For multiple myeloma, the most effective treatment approach involves risk-stratified combination therapy with proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, followed by autologous stem cell transplantation in eligible patients to optimize survival outcomes. 1

Multiple Myeloma Treatment

Initial Risk Stratification

Multiple myeloma treatment should be guided by risk assessment based on:

• Cytogenetic abnormalities (high-risk features include t(4;14), del(17p), t(14;16))
• Disease stage using Revised International Staging System
• Patient factors (age, comorbidities, frailty)

Transplant-Eligible Patients

1. Induction Therapy:

   • Preferred regimen: D-VRd (daratumumab, bortezomib, lenalidomide, dexamethasone) 1
   • Standard regimen: VRd (bortezomib, lenalidomide, dexamethasone) 1
   • Typically administered for 3-6 cycles before transplant 1

2. Autologous Stem Cell Transplantation (ASCT):

   • Should be offered to all eligible patients as it significantly improves progression-free survival (50 months vs. 36 months compared to RVD alone) 2
   • Stem cell collection should be performed early, especially with lenalidomide-based regimens (after 4-6 cycles) 1
   • Consider tandem ASCT if not achieving VGPR after first transplant, particularly for high-risk cytogenetics 1

3. Maintenance Therapy:

   • Lenalidomide maintenance until disease progression is the standard approach 1
   • Consider bortezomib-based maintenance for high-risk patients 1

Transplant-Ineligible Patients

Based on risk stratification:

1. Standard-Risk Patients:

   • Recommended regimen: Lenalidomide-dexamethasone (Rd) continuously as initial therapy 3
   • Particularly beneficial for patients >75 years 4

2. High-Risk Patients:

   • Recommended regimen: Bortezomib-lenalidomide-dexamethasone (VRd) until progression 3
   • VMP (bortezomib-melphalan-prednisone) has shown superior outcomes compared to Rd-R in high-risk patients regardless of age 4

3. Intermediate-Risk Patients:

   • Bortezomib-containing regimens recommended 3
   • Weekly cyclophosphamide-bortezomib-dexamethasone is well-tolerated 3

Relapsed Multiple Myeloma

Treatment selection depends on prior therapy and response:

1. For lenalidomide-refractory patients:

   • DVd (daratumumab, bortezomib, dexamethasone) or
   • KPd (carfilzomib, pomalidomide, dexamethasone) 1

2. For bortezomib-refractory patients:

   • DRd (daratumumab, lenalidomide, dexamethasone) or
   • KRd (carfilzomib, lenalidomide, dexamethasone) 1

3. For triple-refractory patients (refractory to both IMiDs and PIs):

   • Daratumumab-based regimens 3
   • Alkylator-based regimens with panobinostat 3

4. For secondary plasma cell leukemia or extensive extramedullary disease:

   • VDT-PACE (bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) followed by ASCT if eligible 3
   • Daratumumab-based regimens for non-ASCT candidates 3

Supportive Care in Multiple Myeloma

• Bisphosphonates with calcium and vitamin D supplementation
• Antithrombotic prophylaxis for patients on immunomodulators
• Herpes zoster prophylaxis for patients on proteasome inhibitors
• Pneumocystis jiroveci prophylaxis for patients on high-dose steroids
• Seasonal influenza and pneumococcal vaccinations 1

Important Considerations and Common Pitfalls

1. Dose Adjustments:

   • For elderly patients (>75 years), use reduced-dose regimens with dexamethasone 8-20 mg weekly 1
   • Adjust lenalidomide dose based on creatinine clearance 1
   • Use subcutaneous bortezomib over intravenous to reduce peripheral neuropathy risk 1

2. Treatment Delivery:

   • Weekly instead of twice-weekly bortezomib to reduce neuropathy while maintaining efficacy 3
   • Subcutaneous vs. intravenous delivery of bortezomib reduces neuropathy and thrombocytopenia 3

3. Common Pitfalls to Avoid:

   • Delaying transplant evaluation in eligible patients
   • Using fixed-duration therapy instead of continuous therapy
   • Overlooking cytogenetic risk stratification
   • Failing to adjust doses for elderly or frail patients
   • Not monitoring for second primary malignancies 1

Monitoring Response

• Complete response (CR): negative serum/urine immunofixation and <5% plasma cells in bone marrow
• Very good partial response (VGPR): ≥90% reduction of serum M-component
• Regular monitoring should include full blood count, serum and urine electrophoresis, free light chain determination every 3-6 months 1
• Minimal residual disease (MRD) assessment is increasingly used to evaluate treatment efficacy 1

While this overview focuses primarily on multiple myeloma treatment, it's important to note that leukemia treatment approaches differ significantly based on the specific type (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, etc.) and would require a separate detailed discussion.