What are the best treatments for multiple myeloma (Plasma Cell Myeloma)?

From the Guidelines

To combat multiple myeloma, the most effective approach involves a comprehensive treatment plan tailored to the individual's disease stage and overall health, with a strong recommendation for triplet therapies, including bortezomib, lenalidomide, and dexamethasone, or daratumumab, bortezomib, and dexamethasone, for transplant-ineligible patients 1. Treatment typically includes a combination of targeted therapies such as proteasome inhibitors (bortezomib, carfilzomib, ixazomib), immunomodulatory drugs (lenalidomide, pomalidomide, thalidomide), and monoclonal antibodies (daratumumab, isatuximab, elotuzumab). These medications are often used in various combinations with corticosteroids like dexamethasone. For eligible patients, high-dose chemotherapy followed by autologous stem cell transplantation remains a cornerstone treatment that can significantly extend remission periods, as recommended by the European Myeloma Network 1. Newer approaches include CAR T-cell therapy (like idecabtagene vicleucel) and bispecific antibodies for relapsed/refractory cases. Beyond these specific treatments, managing complications is crucial - this includes using bisphosphonates (zoledronic acid, pamidronate) to strengthen bones, maintaining adequate hydration to prevent kidney problems, and treating anemia when necessary, as outlined in the ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of multiple myeloma 1. Regular monitoring through blood tests, imaging, and bone marrow examinations helps track disease progression and treatment effectiveness, with the goal of improving progression-free survival and overall survival, as demonstrated in studies such as the phase III study (MM-020/IFM 07-01) of lenalidomide-low-dose dexamethasone 1. The effectiveness of these treatments stems from their ability to target cancer cells' specific vulnerabilities - proteasome inhibitors disrupt protein degradation pathways critical for myeloma cell survival, while immunomodulatory drugs enhance the immune system's ability to recognize and attack cancer cells. Some key points to consider in the treatment of multiple myeloma include:

• The importance of risk stratification to classify patients for International Staging System stage and for cytogenetically defined high- versus standard-risk groups 1
• The use of novel-agent-based induction and up-front autologous stem cell transplantation in medically fit patients 1
• The consideration of allogeneic stem cell transplantation for young patients with high-risk disease, preferably in the context of a clinical trial 1
• The role of maintenance therapy, such as thalidomide or lenalidomide, in increasing progression-free survival and possibly overall survival 1
• The use of bortezomib-based regimens as a valuable consolidation option, especially for patients who failed to achieve an excellent response after autologous stem cell transplantation 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; After a median follow-up of 64 months, the median PFS was 61.9 months (95% CI: 54.8, NE) in the DRd arm and 34.4 months (95% CI: 29.6,39. 2) in the Rd arm. To combat multiple myeloma, the best approach is to use a combination treatment of daratumumab, lenalidomide, and low-dose dexamethasone (DRd), as it has been shown to improve Progression Free Survival (PFS) and overall survival (OS) in patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplant, with a 44% reduction in the risk of disease progression or death and a 32% reduction in the risk of death 2.

• The key components of this treatment are:
  • Daratumumab 16 mg/kg
  • Lenalidomide 25 mg once daily orally on Days 1–21 of repeated 28-day cycles
  • Low-dose dexamethasone 40 mg/week (or a reduced dose of 20 mg/week for patients >75 years or body mass index [BMI] <18.5)

From the Research

Treatment Options for Multiple Myeloma

The following are some treatment options for multiple myeloma:

• Bortezomib with lenalidomide and dexamethasone (VRd) has shown significant efficacy in newly diagnosed myeloma, improving progression-free and overall survival 3
• Daratumumab with lenalidomide, bortezomib, and dexamethasone (D-RVd) has improved depth of response in patients with transplant-eligible newly diagnosed multiple myeloma 4
• Pomalidomide, bortezomib, and dexamethasone is a treatment option for patients with relapsed or refractory multiple myeloma who previously received lenalidomide, improving progression-free survival 5
• Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant has shown deepening response throughout induction and over the course of treatment 6

First-Line Treatment

First-line treatment options for multiple myeloma include:

• Bortezomib with cyclophosphamide and dexamethasone, currently considered the standard of care as induction regimen before high-dose treatment and transplantation in Germany 7
• Lenalidomide, bortezomib, and dexamethasone, increasingly being used but not yet approved in Germany 7
• Daratumumab in combination with bortezomib, melphalan, and prednisone, recently approved as primary treatment for newly diagnosed patients 7

Considerations

When considering treatment options, factors such as patient age, fitness, and risk stratification should be taken into account 7 Allogeneic stem cell transplantation may be considered for younger patients without relevant comorbidities and with high-risk disease or early relapse after autologous blood stem cell transplantation, but should only be performed within controlled clinical trials and in specialized centers 7