Q&A With Tanya Wildes, MD: Managing Multiple Myeloma in Older Patients

In this question-and-answer session, Cancer Therapy Advisor asked Dr Wildes about the management of multiple myeloma among older patients.
In this question-and-answer session, Cancer Therapy Advisor asked Dr Wildes about the management of multiple myeloma among older patients.

Tanya M Wildes, MD, is an assistant professor of medical oncology at the Washington University School of Medicine in St. Louis, Missouri. Her clinical and research focus is on the management of multiple myeloma and other hematologic cancers among older adults. She also studies risk prediction of falls and geriatric assessment in older patients with myeloma.

In this question-and-answer session, Cancer Therapy Advisor asked Dr Wildes about the management of multiple myeloma among older patients, and how clinical practice is changing as baby boomers reach late adulthood.

Cancer Therapy Advisor (CTA): How are the demographics and incidence of multiple myeloma changing in the United States?

Dr Wildes: Between 2010 and 2030, there is expected to be a 57% increase in the number of myeloma cases diagnosed annually.1 This increase will be largely driven by the aging of the population. One projection estimates that, among individuals age 64 to 84 years, the incidence will increase from 12,700 in 2011 to 2013 to 24,400 in 2032 to 2034 — an increase of over 90%.2 Currently, 2 out of every 3 individuals diagnosed with multiple myeloma are aged 64 to 84. In 15 years, that number will be 3 out of every 4.

CTA: What are the biggest challenges in managing multiple myeloma among older adults?

Dr Wildes: The biggest challenge in managing multiple myeloma in older patients is finding the balance between effectiveness of treatment and toxicity. The trend toward more intensive therapy to obtain deeper responses must be balanced with the real world risk of toxicity.

CTA: How have survival times changed over recent years among patients with myeloma, and have those trends extended to older patients?

Dr Wildes: Advances in treatment have improved survival in patients with multiple myeloma over the past 20 years. There was initially a lag in improvement among the oldest age groups, but more recent estimates have shown greater gains in survival in the older groups, including those over age 75.3-6 The most recent estimates demonstrate improvements in 5-year relative survival rates across age groups, though there has not yet been improvement in 10-year relative survival in the 75 and older group.

CTA: How have newer agents changed the clinical management of myeloma in older patients?

Dr Wildes: The newer agents, including the immunomodulatory agents, the proteasome inhibitors, and most recently, elotuzumab and daratumumab, have dramatically affected the management of older patients. The newer agents are frequently well-tolerated, particularly when dosing and route of administration are individualized for patients based on age, renal function and other comorbidities, and functional limitations.7

CTA: What about toxicities and adverse events associated with myeloma treatment — are older patients at particular risk?

Dr Wildes: Age is associated with increased risk of adverse events of treatment and treatment discontinuation.8 Age greater than 70 increases the risk of early mortality, which is often related to toxicity.9

In older patients with myeloma, renal failure is independently associated with grade 3 to 4 hematologic toxicities.10 The International Myeloma Working Group has developed a frailty model that incorporates age, functional dependence, and comorbidities to categorize older patients as fit, vulnerable or frail; these categories are associated with toxicities and survival.

In general, chronological age is really just a surrogate for physiological aging, which is heterogeneous and can be manifest in an older patient as a number of geriatric syndromes. These include comorbid medical conditions, functional limitations, falls, polypharmacy, sensory impairment, and frailty. With increasing chronological age, geriatric syndromes are more common, hence the associations of toxicity with age.

CTA: How useful are comprehensive geriatric assessments in myeloma management of older adults? What do they entail and how can they inform clinical decision-making?

Dr Wildes: In the world of geriatrics, comprehensive geriatric assessment (CGA) involves a multidisciplinary assessment of a patient, which may take an hour or more, followed by multidisciplinary discussion and treatment recommendations. As used in oncology, geriatric assessment focuses primarily on the assessment part of CGA, with assessment of the geriatric domains described above. Most components of the GA [geriatric assessment] can be self-administered, and only a few minutes of health care provider time is required. GA has been successfully employed in community settings, and alters treatment recommendations about 40% of the time.11,12 In the solid tumor population, primarily self-administered GA covering geriatric domains are predictive of toxicity of chemotherapy.13-15

The role for geriatric assessment in myeloma is emerging, but it appears to be a promising tool to aid in decision-making for older adults with myeloma. In myeloma, the domains of functional status and comorbidities are associated with adverse events and survival.16

Our group has shown that transplant eligibility is independently associated with walking speed on the Timed Up and Go test in older patients with myeloma, suggesting that clinicians are picking up on slowing — independent of comorbidities and performance status.17 The International Myeloma Working Group has proposed treatment pathways depending on the patient's level of fitness.

Further exploration of the role of GA in managing older patients is needed, but it will likely prove a useful tool.

RELATED: Multiple Myeloma: Evaluating Lenalidomide, Bortezomib, and Dexamethasone With Transplantation

CTA: Does the role of thrombosis-prophylactic anticoagulation (such as daily warfarin) change with age among older adults?

Dr Wildes: The immunomodulatory agents have provided a convenient, effective oral treatment for myeloma, but with increased risk of venous thromboembolism (VTE). It was quickly recognized that VTE prophylaxis was required as part of the supportive care for patients on these drugs, yet the optimal strategy was unclear. In a randomized trial of patients receiving thalidomide, 667 patients, including 254 older patients, were randomized to receive aspirin (100 mg daily), low molecular weight heparin (40 mg daily) or warfarin (1.25 mg daily). In the older patients, the rate of VTEs were similar in the aspirin and low molecular weight heparin groups, while the rate was 11.3% higher in the warfarin group, suggesting that warfarin is less effective in this group.18

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