Multiple Myeloma Risks, Explored: Understanding, Treatment, and Beyond
Multiple myeloma, a cancer affecting the bone marrow plasma cells, poses a significant challenge in treating the high-risk subgroup of patients. These individuals experience poorer disease outcomes than expected.
Current novel treatment options for high-risk multiple myeloma include advanced combination drug therapies and cutting-edge cellular immunotherapies. Key recent advances include the approval of CD38-directed monoclonal antibodies Daratumumab and Isatuximab for newly diagnosed multiple myeloma, including high-risk patients. Daratumumab SC has also been approved for treating high-risk smouldering multiple myeloma to delay progression to active disease.
Modern therapies combining proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies achieve deeper, sustained remissions, including in high-risk cytogenetic profiles. Triplet and Quadruplet Regimens, such as those incorporating bortezomib, lenalidomide, and daratumumab, have shown promising results.
CAR T-Cell Therapies, like cilta-cel, anito-cel, and arlo-cel (targeting GPRC5D antigen), demonstrate superior efficacy and promising safety profiles, even in patients with high-risk and extramedullary disease. Anito-cel and arlo-cel are being highlighted for their potent responses and potentially lower toxicities compared to earlier CAR-T therapies.
Bispecific Antibodies targeting GPRC5D and FcRH5 are under investigation, offering off-the-shelf immunotherapy options with promising early results. Selective inhibitors of nuclear export (SINE) such as selinexor represent novel drug classes recently approved to treat relapsed/refractory multiple myeloma, often in combination with backbone regimens.
Research is currently underway to optimize dosage, manage toxicity (e.g., cytokine release syndrome in CAR-T), and individualize treatment based on patient comorbidities and genetic risk. The OPTIMUM/MUK nine clinical trial, involving 107 people with ultra-high risk multiple myeloma, is a notable example. This trial includes further rounds of consolidation treatment and maintenance treatment.
Doctors may prescribe corticosteroids, such as dexamethasone, in the treatment process for high-risk multiple myeloma. However, in some cases, lower doses of lenalidomide and dexamethasone may be prescribed for frail patients. Research indicates that the best evidence treatment - triplet therapy - should be provided whenever possible, consisting of an immunomodulatory drug, a proteasome inhibitor drug, and a steroid.
Despite these advances, people with high-risk multiple myeloma still face a challenging treatment process. The presence of frailty, extramedullary disease, plasma cell leukemia, high-risk cytogenetic abnormalities, relapsing sooner than expected, R ISS-3 (Revised International Staging System, stage III) with a serum β2 microglobulin level greater than 5.5 milligrams per liter (mg/l), indicates that a person's multiple myeloma is in the high-risk subgroup.
Research into novel therapy options would be beneficial for providing better care to people with high-risk multiple myeloma. Treatment decisions are now based on a person's frailty and other diseases, rather than just age. The treatment approach to high-risk multiple myeloma may involve induction therapy, autologous stem cell transplants, and maintenance therapy. Between 10-20% of people with multiple myeloma die within 2-3 years following diagnosis.
In conclusion, combination drug therapies involving monoclonal antibodies plus standard myeloma agents, advanced CAR T-cell therapies targeting novel antigens, and emerging bispecific antibodies currently constitute the main novel options for high-risk multiple myeloma, many of which are available through clinical trials or have recently received regulatory approval. These approaches aim not only at extending survival but also at improving quality of life and potentially reaching functional cures in this historically difficult-to-treat subgroup.
- In the treatment of high-risk multiple myeloma, doctors may utilize advanced combination drug therapies, such as those that incorporate monoclonal antibodies like Daratumumab and Isatuximab.
- Researchers are investigating novel therapies for high-risk multiple myeloma, including off-the-shelf immunotherapy options, like bispecific antibodies targeting GPRC5D and FcRH5.
- Modern research focuses on optimizing the dosage and managing toxicity of these novel treatments, taking into account a patient's comorbidities and genetic risk.
- CAR T-Cell Therapies, such as cilta-cel, anito-cel, and arlo-cel, targeting GPRC5D antigen, demonstrate superior efficacy and improved safety profiles in high-risk and extramedullary disease cases.
- In some instances, doctors prescribe dexamethasone along with corticosteroids as part of the treatment process for high-risk multiple myeloma, but low-dose lenalidomide and dexamethasone may be more suitable for frail patients.
- High-risk multiple myeloma, despite recent advancements in treatment options like CD38-directed monoclonal antibodies and CAR T-cell therapies, still requires further research for the development of better therapeutic approaches, aiming not only for an extended survival but also improved quality of life and potentially functional cures.
