Multiple myeloma (MM) exists in the spectrum of plasma cell dyscrasias and is a malignant proliferation of clonal plasma cells causing end organ damage. NCI SEER data estimated over 35,000 new cases of MM in 2024, accounting for 2% of all cancers and 19% of all hematologic malignancies in the United States.
Standard treatment for newly diagnosed multiple myeloma (NDMM)
Treatment for NDMM is induction chemotherapy, followed by consolidation with high-dose alkylating chemotherapy and peripheral blood autologous hematopoietic stem cell transplant (AHCT), and maintenance therapy with 1-2 drugs to prevent disease recurrence.
In the last five years, the use of four-drug regimens for induction has become the standard of care in NDMM patients. Multiple trials have shown significant improvements in minimal residual disease (MRD) negativity, progression free survival (PFS) and overall survival (OS) with the inclusion of anti-CD38 antibodies to three-drug regimens consisting of immunomodulatory drugs (iMIDS), and proteosome inhibitors (PIs).
Data from the GRIFFIN and PERSEUS trials established daratumumab, lenalidomide, bortezomib and dexamethasone (Dara-RVD) as the new standard of care in NDMM. In the PERSEUS trial, the stringent complete remission rate (sCR) of patients treated with Dara-RVD followed by AHCT was 69% with 75% achieving MRD negativity. Trials such as MASTER and FORTE have examined carfilzomib as the PI of choice in combination therapies (Dara-KRD), with remarkable results albeit slightly higher toxicity. The IMROZ and GMMG-HD7 trials evaluating the second generation anti-CD38 antibody, isatuximab, have led to the FDA approval of Isa-RVD for NDMM patients. Similarly, the use of daratumumab as single agent or in combination with lenalidomide as maintenance therapy is changing the evolving landscape of myeloma treatment. The ongoing DRAMMATIC trial is an example of this.
Regardless of the induction or maintenance strategy used, all NDMM patients should be referred to a cellular therapy physician upon diagnosis for evaluation and consideration of AHCT. No trial has shown chemotherapy consolidation alone as superior to transplant in NDMM. The decision to pursue consolidation with high-dose chemotherapy and AHCT is made by a physician with training and expertise in the complex care patients undergoing cellular therapy require.
Relapsed/refractory multiple myeloma (RRMM)
Despite advances in treating NDMM patients, the majority will eventually relapse. MM has seen the most drug approvals in the relapse/refractory setting than any other cancer in the last 10 years. Using chimeric antigen receptor T cells (CAR-T) and bispecific T-cell engager antibody therapy (BiTEs) has completely changed how RRMM is treated. Ciltacabtagene autoleucel (Carvykti) and Idecabtagene vicleucel (Abecma) are both anti-B-cell maturation agent (BCMA) CAR-T cells approved in patients with RRMM. Carvykti is currently approved as second line treatment based on data from the CARTITUDE-4 trial and Abecma is approved as third line treatment based on the KarMMA-3 trial. All patients with myeloma who relapse after initial therapy, should be promptly referred to a cellular therapy physician authorized to infuse these products. The leukapheresis, T-cell manufacturing, and infusion of CART cells can take up to six weeks. Thus, early referral is key to better patient outcomes. In addition, CART cell therapy is associated with a specific side effect profile that includes cytokine release syndrome (CRS) and neurotoxicity (ICANS) among others, that requires expert level care in an authorized treatment center.
BiTEs are novel immunotherapeutic drugs that enhance the host’s immune T-cell response by bringing together T-cells and malignant cells. BiTEs against BCMA and GPRC5D include teclistamab, elranantamab and talquetamab. These agents are currently approved for RRMM after four or more lines of therapy and require an initial hospitalization with a specific dose-ramp up schedule due to the risk of CRS and ICANS. Once the treatment dose is achieved, and if no complications arise, future cycles can be given in the outpatient setting.
Future of myeloma treatment
Research in multiple myeloma continues to evolve, with numerous clinical trials in RRMM patients evaluating novel “off-the-shelf” allogeneic CART products, combinations of cellular therapy and immunotherapy, third and fourth generation CART cells targeting more than one antigen, among others. Northside Cancer Institute has a robust clinical trial platform to benefit this patient population.
Impact on patient outcomes
In the last 20 years, the survival rates for patients with multiple myeloma have increased dramatically due to earlier diagnosis and improved treatment options. The Cellular and Immunotherapy Program at Northside Hospital Cancer Institute and Blood and Marrow Transplant Group of Georgia boasts some of the country's best survival and quality outcomes. Together with local oncologists, patients treated at Northside have the opportunity to live decades after an initial diagnosis of multiple myeloma.
Learn more about multiple myeloma treatment at Northside Hospital Cancer Institute.
