What are the new target therapies in Multiple Myeloma (MM)?

From the Guidelines

The most effective new target therapy in multiple myeloma (MM) is the combination of bortezomib, lenalidomide, and dexamethasone, which has shown high response rates and improved progression-free survival in patients with newly diagnosed MM, as demonstrated in a phase III trial 1.

Key Findings

• The combination of bortezomib, lenalidomide, and dexamethasone has been shown to be active and well-tolerated in patients with newly diagnosed MM, with a partial response rate of 100% and a complete response rate of 52% 1.
• The 18-month progression-free survival rate was 75% and the overall survival rate was 97% after lenalidomide, bortezomib, and dexamethasone with or without autologous stem cell transplantation (SCT) 1.
• Other effective therapies for MM include daratumumab, elotuzumab, and carfilzomib, which have been shown to improve response rates and progression-free survival in patients with relapsed or refractory MM 1.

Treatment Selection

• Treatment selection depends on prior therapies, patient comorbidities, and availability, with many of these agents currently being studied in earlier treatment lines to maximize their benefit.
• Triplet regimens, such as bortezomib, lenalidomide, and dexamethasone, should be used as the standard therapy for patients with MM, unless the patient is elderly or frail, in which case doublet regimens may be considered 1.

Important Considerations

• Patients treated with proteasome inhibitors should receive herpes zoster prophylaxis, and full-dose aspirin is recommended with immunomodulator-based therapy 1.
• Subcutaneous bortezomib is the preferred method of administration for patients with pre-existing or high-risk peripheral neuropathy 1.

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.

New target therapy in MM: Daratumumab is a new target therapy for multiple myeloma (MM).

• The MAIA trial 2 demonstrated that daratumumab in combination with lenalidomide and dexamethasone (DRd) improved progression-free survival (PFS) compared to lenalidomide and dexamethasone (Rd) alone in patients with newly diagnosed MM ineligible for autologous stem cell transplant.
• The results showed a 44% reduction in the risk of disease progression or death in patients treated with DRd, with a median PFS of 61.9 months in the DRd arm and 34.4 months in the Rd arm.
• Key benefits of daratumumab include improved PFS, overall response rate, and minimal residual disease (MRD) negativity rate compared to Rd alone.

From the Research

New Target Therapies in Multiple Myeloma (MM)

• The treatment of newly diagnosed multiple myeloma is constantly changing with the advent of novel therapies 3.
• Recent advances in therapies have resulted in longer time to remission and overall survival 3.
• Targeted therapy with monoclonal antibodies such as Daratumumab has improved stringent complete response to 39% 3.

Combination Therapies

• The combination of bortezomib with lenalidomide and dexamethasone (VRd) has shown significant efficacy in the setting of newly diagnosed myeloma 4.
• The addition of bortezomib to lenalidomide and dexamethasone resulted in significantly improved progression-free and overall survival and had an acceptable risk-benefit profile 4.
• The combination of isatuximab with VRd (isatuximab-VRd) was more effective than VRd as initial therapy in patients with newly diagnosed multiple myeloma who were ineligible to undergo transplantation 5.

Comparison of Therapies

• The KRd regimen (carfilzomib, lenalidomide, and dexamethasone) did not improve progression-free survival compared with the VRd regimen in patients with newly diagnosed multiple myeloma, and had more toxicity 6.
• The VRd triplet regimen remains the standard of care for induction therapy for patients with standard-risk and intermediate-risk newly diagnosed multiple myeloma 6.

Future Directions

• Future concepts will evaluate cellular treatments and other innovative immunotherapies in first-line treatment in curative intention 7.
• Despite successful treatment options, specific difficult-to-treat subgroups, especially patients with high-risk myeloma remain with inferior prognosis and a clear unmet need for novel therapeutic strategies 7.