Challenges and Solutions Treating Multiple Myeloma

In a recent review, the challenges of treating very elderly (over 80-years-old) patients with multiple myeloma were discussed and potential solutions were outlined.

According to the study published in Clinical Interventions in Aging, very elderly patients do not benefit from newer drugs like younger patients do. This is due to organ dysfunction, poor resilience to physiological stressors, reduced functional status, and comorbidities.

Researchers said that diagnosing myeloma, assessing the need for treatment, and choosing treatment intensity are highly complex for very elderly patients.

Diagnosis

Multiple myeloma is preceded by asymptomatic monoclonal gammopathy of undetermined significance (MGUS). However, most patients diagnosed with MGUS do not progress to myeloma, so it is critical for a physician to determine whether the patient has myeloma or MGUS with unrelated organ dysfunction.

Patients with myeloma also can have unexplained anemia, bone pain, hypercalcemia, renal dysfunction, fatigue, spinal cord compression (SCC), recurrent bacterial infections, and symptoms of hyperviscosity.

Approximately 40% of patients with myeloma have unexplained renal impairment, SCC, fracture, or profound hypercalcemia.

Very elderly patients showing symptoms of anemia, renal impairment, or bone pain require detailed evaluation since those symptoms could be unrelated, according to the article.

In this group of patients, researchers wrote there is a typical delay of 6 months between onset of symptoms and diagnosis, and approximately 50% of diagnosed patients need 3 visits to a general practitioner before a referral is made.

For diagnosis, the demonstration of a clonal population of plasma cells needs to be taken from either bone marrow or within a bony extramedullary plasmacytoma. A side effect of significant bleeding may occur from these procedures for very elderly patients because they may not be able to lay in the ideal position, may be taking antiplatelet agents, and a paraprotein can interfere with fibrin production, according to the study.

Osteoporosis could also present problems in obtaining a trephine biopsy sample. Some clinicians may only perform aspiration or could omit the test completely.

Need for Treatment and Fitness for Treatment

Starting chemotherapy should be a decision made by a specialist myeloma multidisciplinary team that includes the patient and their family. Treatment recommendations are made after end-organ damage from myeloma has been identified.

According to the review, a myeloma-specific comprehensive geriatric assessment (CGA) divides patients into groups of variable fitness (fit, intermediate fitness, frail) to guide treatment schedules. However, any patient who is over 80 years will automatically be designated as frail, solely based on age.

An alternative CGA tool that assesses renal and respiratory function in patients could be a better way to evaluate elderly patients.

Researchers said the clinician should take age, performance status, a CGA tool, and views of the patient and their families into account when creating a treatment plan. Clinical judgement by the clinician is also an important part of this.

Attenuated chemotherapy could reduce drug discontinuations in this population, but some patients will not be able to receive attenuated treatment and should be identified early.

Supportive Care for the Very Elderly

Input from specialists in pain medication, orthopedic surgery, interventional radiology, and palliative care is required for the supportive care of myeloma patients, according to researchers.

Skeletal complications in particular can be debilitating and 5% of patients develop SCC with myeloma.

Researchers said that high-dose dexamethasone should start as soon as SCC is suspected and a plan that involves surgery or radiotherapy should be implemented.

Radiotherapy, and sometimes orthopedic surgery, could be the appropriate treatment option for some patients and can treat bony lesions or fractures.

For this population, paracetamol is safe and preferred over nonsteroidal anti-inflammatory drugs and opioids for pain relief.

Bisphosphonates could also be effective for treatment and can stop conditions such as osteonecrosis.

With bisphosphonates, researchers said that calcium and vitamin D supplements should be taken to avoid hypocalcaemia.

To manage symptoms of anemic patients, they can receive red blood cell transfusions, consideration of IV iron infusion, and erythropoietin-stimulating agents in some patients.

Dexamethasone treatment can also reverse renal dysfunction in approximately 50% of patients with myeloma. Renal failure can be caused by damage to renal tubules by free light chains, NSAID usage, dehydration, hypercalcemia, and infection.

Patients also have an increased risk of venous thromboembolism (VTE) and is more common with elderly patients.

Low-molecular-weight-heparin prophylaxis should be used to treat high-risk patients, but may not be an effective treatment for very elderly patients due to poor eyesight, lack of dexterity, and low confidence with self-injecting, the researchers wrote. However, aspirin could be a suitable treatment.

Approximately 10% of myeloma patients die from infection within 60 days of diagnosis. Since elderly patients are prone to infections, prophylactic fluconazole and acyclovir are prescribed with chemotherapy.

Combination Chemotherapy Treatment for Fitter Very Elderly Patients

Large clinical trials have led to a treatment approach for patients who are not eligible for an autologous stem cell transplant (ASCT). According to the study, those patients are over 65-years-old or younger, but have prohibitive comorbidities.

Clinicians should take into account age, CGA, performance status, clinical assessment when stratifying patients into fit patients who can receive combination therapies, frail patients needing attenuated therapies, and patients who can only receive palliative care, according to the authors.

Treatment with thalidomide and alkylating agents are generally avoided for treating very elderly patients due to higher toxicity.

Previous study data indicates a first-line treatment of lenalidomide-dexamethasone for fit patients.

Patients with renal disease or patients with aggressive disease requiring rapid paraprotein reduction subcutaneous bortezomib-dexamethasone is the preferred treatment.

For frail patients, lenalidomide can be used to start, but a dose reduction is typically necessary.

Patients with cognitive impairment or poor function, palliation could be the preferred treatment and low-dose steroids can offer symptom relief.

Relapse

According to the study, patients with asymptomatic serological replace can have a treatment delay until there is evidence of organ dysfunction. Rapidly rising paraprotein indicates that the disease needs retreatment.

Rechallenging with lenalidomide or bortezombi can be an appropriate treatment if there was a response within 12 months. Switching regimens is recommended in refractory disease or short-term response.

Patients who relapse after bortezomib and lenalidomide can be fit enough for further treatment.

New treatments, such as the proteasome inhibitor carfilzomib, have been found effective in relapsed myeloma with a reduced toxicity compared with bortezomib.

Further treatment could be deemed inappropriate depending on the frailty of the patient and their wishes.

End-Of-Life Care

End-of-life is typically considered the last 12 months of life, and in some patients, can be the diagnosis of myeloma. A holistic needs assessment is an important tool that lets patients talk freely about their needs and wishes.

Open and honest dialogue about prognosis is critical for the patient and their family to make choices when it comes to treatment options. Since myeloma is incurable, stopping chemotherapy and starting palliative care can sometimes be the best option for very elderly patients.

Researchers conclude that although myeloma is challenging to treat and diagnose in very elderly patients, assessment of fitness for the appropriate treatment is needed to ensure proper and effective care for these patients.