`Multiple myeloma is a cancer that hits older adults hardest, with 45% of new cases diagnosed in people aged 75 and older. 

The number of people over 80 being diagnosed has doubled in recent years. But there’s a problem: older patients are often left out of clinical trials, so treatments aren’t always made for them. 

While newer drugs have helped younger, healthier patients, survival rates for those over 80 have not improved over the last two decades. 

Keep reading to learn more about the challenges of treating myeloma in older adults and how they’re managing the disease.

The Interaction Between MM and Aging

There’s a night and day difference between the bones of a young adult and one far past their prime, and that’s not the only thing. Here’s how MM affects every aspect of an elderly’s body.

Bone Marrow and Blood Dysfunction

Aging naturally reduces the regenerative capacity of the bone marrow. Multiple myeloma worsens this decline by crowding out healthy cells. The result is severe blood imbalances:

  • Anemia: Myeloma disrupts red blood cell production, causing fatigue, shortness of breath, and increased strain on the heart. Many patients require blood transfusions or erythropoiesis-stimulating agents.
  • Neutropenia: Reduced white blood cells leave the immune system weakened, heightening the risk of infections like pneumonia and sepsis. Preventative antibiotics or G-CSF are often necessary.
  • Thrombocytopenia: Low platelet levels lead to bleeding gums, bruising, and increased risk of severe bleeding from minor injuries. Platelet transfusions may be required in severe cases.

Elderly patients, whose bone marrow function is already declining, are especially vulnerable to these disruptions. This makes treatment with bone marrow-suppressing drugs challenging and requires careful monitoring of blood counts.

Bone Fragility and Hypercalcemia

Bone health is a major concern in MM because the disease accelerates bone resorption while suppressing new bone formation. 

This imbalance, bought on by excessive osteoclast activity and suppressed osteoblast function, leads to:

  • Lytic bone lesions: Weak spots in the skeleton that are visible on X-rays or MRIs.
  • Pathologic fractures: Often occurring in weight-bearing areas like the spine or hips, limiting mobility and reducing independence.
  • Bone pain: A common and often debilitating symptom requiring strong pain management strategies.

MM also raises calcium levels in the blood (hypercalcemia), causing symptoms like nausea, confusion, constipation, and kidney strain. 

Bisphosphonates (e.g., zoledronic acid) or denosumab can slow bone destruction, reduce fracture risk, and treat hypercalcemia. 

A good amount of hydration, alongside calcium and vitamin D supplementation, helps maintain healthy bone metabolism.

Kidney Damage

Myeloma cells produce excess monoclonal proteins (light chains) that accumulate in the kidneys, causing cast nephropathy (myeloma kidney). 

Over time, this damages the kidneys’ ability to filter waste, especially in elderly patients that have renal insufficiency. Renal impairment complicates treatment because many MM drugs require dose adjustments for reduced kidney function.

Strategies to protect the kidneys include:

  • Aggressive hydration to flush light chains.
  • Renal dosing of drugs like lenalidomide and bisphosphonates.
  • Avoiding nephrotoxic agents, such as certain antibiotics or nonsteroidal anti-inflammatory drugs.

Immune System Impairment

Multiple myeloma suppresses normal antibody production (hypogammaglobulinemia), leaving patients vulnerable to infections. Common infections include respiratory tract infections, urinary tract infections, and shingles. Elderly patients face even greater risks because age weakens immune function.

Strategies to prevent infections include:

  • Vaccinations: Influenza, pneumococcal, and shingles vaccines are standard.
  • Antiviral prophylaxis: Drugs like acyclovir are used to prevent shingles.
  • Intravenous immunoglobulin (IVIG): Provides passive immunity for patients with weak immune systems.

Frailty and Cognitive Decline

Frailty—a state of reduced strength and resilience—affects many elderly patients. 

It worsens with MM and its treatments, manifesting as muscle loss, fatigue, weight loss, and reduced physical function. Cognitive impairments, such as memory loss or confusion, can further complicate adherence to complex treatment regimens.

Frailty is measured using tools like the International Myeloma Working Group Frailty Score, which evaluates physical fitness, comorbidities, and overall health to guide treatment intensity.

Treatment For Multiple Myeloma In The Elderly

Common Treatments For Multiple Myeloma In The Elderly

Treatment is usually personalized, focusing on combinations of targeted therapies:

Proteasome Inhibitors

These drugs prevent myeloma cells from degrading abnormal proteins, leading to their death. 

Common examples:

  • Bortezomib: Given subcutaneously to reduce the risk of peripheral neuropathy.
  • Carfilzomib: Effective in advanced cases but requires heart monitoring.
  • Ixazomib: An oral option ideal for frail patients.

Immunomodulatory Drugs (IMiDs)

IMiDs boost immune responses and disrupt myeloma cell growth.

  • Lenalidomide: Widely used due to its oral dosing and flexibility for frail patients.
  • Pomalidomide: A second-line option for relapsed or refractory disease.

Monoclonal Antibodies

These drugs target specific proteins on myeloma cells:

  • Daratumumab: Targets CD38 to kill cancer cells and improve immune function.
  • Elotuzumab: Activates immune cells to attack myeloma.

Corticosteroids

Dexamethasone reduces inflammation and kills myeloma cells but may cause blood sugar spikes, mood swings, or muscle weakness, requiring dose adjustments.

Challenges in Treating Elderly Patients

Here’s a brief look at all the common challenges.

Balancing Disease Control with Side Effects

Older patients tolerate treatments differently due to:

  • Reduced organ reserve: Decreased liver and kidney function slow drug metabolism and clearance.
  • Comorbidities: Chronic conditions like diabetes or heart disease heighten risks from therapy side effects.
  • Neuropathy risk: Drugs like bortezomib can cause peripheral neuropathy, which may limit walking or hand function in elderly patients.

For this reason, treatment regimens always need to balance disease control with quality of life. Dose adjustments and simplified regimens are often necessary to prevent serious toxicity.

Limiting Treatment Intensity

Intensive therapies like high-dose chemotherapy and autologous stem cell transplantation (ASCT) are rarely suitable for elderly patients due to their toxicity. Instead, less intensive options are preferred, such as:

  • Oral regimens: Convenient for older patients who may have difficulty traveling to infusion centers.
  • Dose-modified triplet regimens: Combining three drugs at reduced doses to maintain effectiveness while minimizing side effects.

Lenalidomide: A Key Treatment for Elderly Multiple Myeloma Patients

Lenalidomide is an important medicine for treating multiple myeloma in older adults. It works well, comes as a pill, and doctors can adjust the dose depending on the person’s health. The dose depends on kidney function and how well the patient can handle the treatment.

Common Doses and When They’re Used

  • Lenalidomide 5 mg/day: This dose is for people with very poor kidney function (kidneys clearing less than 30 mL of blood per minute). It helps reduce serious side effects, like very low blood cell levels, while still controlling the disease.
  • Lenalidomide 10 mg/day: This dose is often given after the first phase of treatment to keep the disease under control (called maintenance therapy). It’s gentler and works well for people with moderate health issues.
  • Lenalidomide 15 mg/day: Doctors usually use this dose during the first phase of treatment (induction therapy) for people who can handle slightly stronger treatment. Regular check-ups are needed to watch for side effects like low white blood cell levels or feeling very tired.
  • Lenalidomide 25 mg/day: This is the full dose used for people who are generally healthy without other serious medical problems. It’s often part of more intense treatment to slow the disease. Side effects, like tiredness or low blood counts, are more common at this dose, so doctors check patients closely.

How Side Effects Are Handled

Lenalidomide can cause some problems, including low blood counts (which may cause infections or tiredness), blood clots, or fatigue. To avoid blood clots, doctors prescribe blood thinners like aspirin. Regular blood tests help catch and manage any side effects before they become serious.

Conclusion

At the end of the day, it’s about improving lives. Multiple myeloma in older adults may come with challenges, but with treatments like lenalidomide, doctors can adjust care to fit the individual. It’s not only about surviving the disease, it’s about living well through it.

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