From the Guidelines
The most effective treatment for multiple myeloma typically involves a combination approach, including a proteasome inhibitor, an immunomodulatory drug, and a corticosteroid, with consideration of high-dose chemotherapy and autologous stem cell transplantation for eligible patients 1.
Initial Therapy
Initial therapy for multiple myeloma usually includes a three-drug regimen, such as RVd (lenalidomide, bortezomib, and dexamethasone) given in 21-day cycles. This approach is supported by the 2019 ASCO and CCO joint clinical practice guideline, which recommends individualized treatment based on disease-specific and patient-specific factors, including the use of novel agents and steroids 1.
Eligibility for Transplantation
For eligible patients under 70-75 years without significant comorbidities, high-dose chemotherapy followed by autologous stem cell transplantation is recommended after 4-6 cycles of initial therapy. This approach is supported by the 2017 ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of multiple myeloma 1.
Maintenance Therapy
Maintenance therapy, often with lenalidomide 10-15mg daily, typically follows to prolong remission. The 2019 ASCO and CCO joint clinical practice guideline recommends continuous therapy over fixed-duration therapy when initiating an immunomodulatory drug or proteasome inhibitor-based regimen 1.
Relapsed Disease
For relapsed disease, treatment depends on previous therapies and may include newer agents like daratumumab, isatuximab, or BCMA-targeted therapies like belantamab mafodotin. The 2017 NCCN clinical practice guidelines in oncology provide a list of preferred regimens for previously treated multiple myeloma, including bortezomib/dexamethasone, carfilzomib/dexamethasone, and daratumumab/bortezomib/dexamethasone 1.
Supportive Care
Supportive care is essential and includes bisphosphonates (zoledronic acid 4mg IV monthly) to prevent bone complications, pain management, and prevention of infections. Treatment effectiveness varies based on disease characteristics, with high-risk cytogenetic features often requiring more aggressive approaches.
From the FDA Drug Label
14 CLINICAL STUDIES 14. 1 Newly Diagnosed Multiple Myeloma Combination Treatment with Lenalidomide and Dexamethasone in Patients Ineligible for Autologous Stem Cell Transplant MAIA (NCT02252172), an open-label, randomized, active-controlled trial, compared treatment with DARZALEX 16 mg/kg in combination with lenalidomide and low-dose dexamethasone (DRd) to treatment with lenalidomide and low-dose dexamethasone (Rd) in patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplant.
Efficacy was evaluated by progression free survival (PFS) based on International Myeloma Working Group (IMWG) criteria. MAIA demonstrated an improvement in Progression Free Survival (PFS) in the DRd arm as compared to the Rd arm; the median PFS had not been reached in the DRd arm and was 31.9 months in the Rd arm (hazard ratio [HR]=0.56; 95% CI: 0.43,0.73; p<0. 0001), representing 44% reduction in the risk of disease progression or death in patients treated with DRd.
Treatment for multiple myeloma involves the use of daratumumab in combination with lenalidomide and dexamethasone, as demonstrated by the MAIA trial 2 and 2.
- The combination of daratumumab, lenalidomide, and dexamethasone (DRd) showed an improvement in Progression Free Survival (PFS) compared to lenalidomide and dexamethasone (Rd) alone.
- The median PFS was not reached in the DRd arm, while it was 31.9 months in the Rd arm, representing a 44% reduction in the risk of disease progression or death.
- The treatment also demonstrated an improvement in overall survival (OS), with a 32% reduction in the risk of death in patients treated with DRd.
From the Research
Treatment Options for Multiple Myeloma
- The treatment of multiple myeloma has evolved with the approval of numerous agents over the past decade, leading to improved overall survival and the possibility of deep responses, including a minimal residual disease-negative state 3.
- For patients with newly diagnosed multiple myeloma, the combination of bortezomib, lenalidomide, and dexamethasone (VRd) is considered a standard of care as an induction regimen before high-dose treatment and transplantation 4.
- The addition of bortezomib to lenalidomide and dexamethasone has been shown to improve progression-free and overall survival in patients with newly diagnosed multiple myeloma who are not planned for immediate autologous stem-cell transplant 5.
- Carfilzomib, a next-generation proteasome inhibitor, in combination with lenalidomide and dexamethasone (KRd), has shown promising efficacy in phase 2 trials, but did not improve progression-free survival compared to VRd in a phase 3 trial 6.
Relapsed or Refractory Multiple Myeloma
- For patients with relapsed or refractory multiple myeloma who previously received lenalidomide, the combination of pomalidomide, bortezomib, and dexamethasone has been shown to improve progression-free survival compared to bortezomib and dexamethasone alone 7.
- The treatment of relapsed or refractory multiple myeloma often involves the use of novel agents, such as pomalidomide, and combination regimens, including bortezomib and lenalidomide 3.
Emerging Therapies
- Emerging therapies, including targeted approaches, immune-based therapies, and drugs with novel mechanisms of action, offer the promise of more individualized approaches in the management of patients with multiple myeloma 3.
- Trials evaluating chimeric antigen receptor T cells targeting B-cell maturation antigen are ongoing and may provide new treatment options for patients with multiple myeloma 3.