Multiple myeloma is a cancer of plasma cells, which are a type of white blood cell found in the bone marrow. It primarily affects older adults, often those aged 65 and above, with many patients being seniors over 75. Treating multiple myeloma in seniors presents unique challenges because older patients frequently have other health issues and may not tolerate aggressive therapies well. Therefore, the best therapies for multiple myeloma in seniors focus on balancing effectiveness against side effects while considering overall health status and frailty.
For elderly patients who are generally considered *ineligible* for intensive treatments like autologous stem cell transplantation (ASCT), which involves high-dose chemotherapy followed by reinfusion of their own stem cells, treatment usually consists of combination drug regimens that can be given continuously or until disease progression. These regimens aim to control the cancer effectively but with manageable toxicity.
One cornerstone approach involves **triplet or quadruplet drug combinations** that include:
– **Immunomodulatory drugs (IMiDs)** such as lenalidomide: These drugs help stimulate the immune system to attack myeloma cells and also directly inhibit tumor growth.
– **Proteasome inhibitors (PIs)** like bortezomib: These interfere with protein degradation inside cancer cells causing them to die.
– **Monoclonal antibodies**, especially daratumumab: This antibody targets CD38 on myeloma cells leading to their destruction by immune mechanisms.
– **Corticosteroids** such as dexamethasone: They reduce inflammation and have direct anti-myeloma effects.
A commonly used regimen for transplant-ineligible elderly patients is *lenalidomide plus dexamethasone* (Rd). This doublet has been favored due to its balance between efficacy and tolerability compared to older alkylator-based combinations like melphalan-prednisone-thalidomide or melphalan-prednisone-bortezomib. Studies showed Rd improved progression-free survival and overall survival in seniors better than some traditional regimens.
Adding daratumumab to lenalidomide-dexamethasone creates a triplet therapy known as DRd, which has demonstrated deeper responses including higher rates of complete remission and minimal residual disease negativity even among those aged 75 years or older. This quadruplet approach—adding monoclonal antibody therapy—has become increasingly standard because it improves outcomes without substantially increasing severe side effects when carefully managed.
Other treatment considerations specific to seniors include:
– **Dose adjustments:** Older adults often have reduced kidney function or other organ impairments affecting drug metabolism; doses may need lowering accordingly.
– **Side effect management:** Seniors are more prone to fatigue, infections due to immunosuppression, neuropathy from certain drugs like bortezomib or thalidomide, blood count suppression causing anemia or bleeding risk—all requiring close monitoring.
– **Bone health support:** Myeloma weakens bones leading to fractures; bisphosphonates or newer agents help strengthen bones alongside systemic therapy.
– **Supportive care:** Pain control, infection prevention through vaccines/antibiotics if needed, nutritional support, physical therapy for weakness—all crucial parts of managing elderly patients holistically.
In some cases where frailty is significant but disease burden demands intervention, less intensive doublet therapies might be chosen initially with careful escalation based on tolerance. For example:
– Lenalidomide plus low-dose dexamethasone
– Bortezomib plus dexamethasone
Emerging immunotherapies beyond daratumumab are also under investigation specifically tailored toward elderly populations who cannot undergo transplant but could benefit from novel agents targeting different pathways involved in myeloma growth.
While ASCT remains an option mainly reserved for younger fit individuals due its intensity requiring good organ function and performance status; ongoing research explores safer conditioning re