Chapter 4 – Treatment of elderly patients with myeloma

Contributors: Eileen M Boyle, Charline Legrand, Hélène Demarquette, Stéphanie Guidez, Charles Herbaux, Xavier Leleu, and Thierry Facon

8 – Supportive care

In addition to myeloma-specific therapies, supportive care is essential in patients with myeloma. This includes management of anemia, pain, hypercalcemia, bone disease, infection prophylaxis, and nutrition.

Anemia

Anemia may be better tolerated in older patients who are not very physically active. Anemia is a greater concern in patients with ischemic heart disease, chronic obstructive lung disease, and a history of stoke. The hemoglobin goals are thus highly patient dependent. Anemia should therefore be treated with a sensible use of transfusions and erythropoiesis-stimulating agents.

Pain

The use of narcotic analgesics should strike a balance between adequate pain relief with resultant improvement in QOL and adverse effects such as drowsiness, confusion, and constipation. Radiotherapy is an alternative form of local treatment for painful osteolytic lesions [95].

Hypercalcemia

Hypercalcemia is treated with hydration, bisphosphonates, and corticosteroid therapy. Typically, pamidronate (90 mg over 2 hours; 30–60 mg with renal dysfunction) or zoledronic acid (4 mg; 2–3 mg with mild-to-moderate renal impairment) are used.

Bone disease

Bisphosphonates should be administered to myeloma patients with or without osteolytic disease or in patients with myeloma receiving other forms of osteoporosis treatment. Clodronate reduces the progression of lytic lesions by 50% (12% versus 24% in the placebo arm) and the time to first non-vertebral fracture [96]. Intravenous pamidronate was associated with a significant decrease in ostolytic lesions, skeletal-related events (SREs) (21% versus 41% in the placebo group), pain, and deterioration of QOL [97]. Zoledronic acid is as effective as pamidronate in preventing SREs [98]. More importantly, in the Myeloma IX trial zoledronic acid was associated with a significant reduction in the number of lytic lesions before progression (27% versus 35%) and an improvement in both PFS (2 months) and OS (5.5 months) in comparison with clodronate [99]. The optimal treatment duration is unknown but should at least be continued for a year on a monthly basis [92]. Calcium and vitamin D are recommended to avoid symptomatic hypocalcemia. Two major complications associated with bisphosphonate treatment are osteonecrosis of the jaw (ONJ) and renal failure. ONJ is characterized by exposed bone in the mouth that does not heal within 6–8 weeks of therapy. In the myeloma IX trial, 4% of patients that received zoledronic acid developed ONJ; this was not related to age. As myeloma is relatively sensitive to radiotherapy, this treatment modality is an appropriate form of local treatment for painful osteolytic lesions and vertebral disease threatening or resulting in chord or root compression, or as a consolidation treatment to a pathologic fracture. MM accounts for 11% of all neoplastic chord compression. In the largest retrospective series to date, radiotherapy alone improved motor function in 75% of patients with MM and spinal cord compression (SCC) [100]. One year local control was 100%, and 1 year survival was 94%. Surgery may also play a role in the management of impending myeloma-related fractures and should be considered based on frailty and comorbidities. Kyphoplasty or vertebroplasty should be considered for vertebral collapse resulting in pain unresponsive to medications or to stabilize vertebrae at risk of fracture. Balloon kyphoplasty was shown to reduce pain and improve function in patients with cancer vertebral compression fractures compared with non-surgical management [101]. Patients with significant scoliosis should undergo physical therapy. Breathing exercises and incentive spirometry are important to reduce the risk of lung infections. Smoking cessation should be encouraged to reduce predisposition to lung problems.

Infection

Infection prophylaxis is crucial when corticosteroids are used. Depending on the centers, trimethoprim-sulfamethoxazole and acyclovir are used. Fluconazole is not recommended by the European Conference on Infections in Leukemia (ECIL) guidelines [102]. Elderly patients, especially when treated with bortezomib, are susceptible to varicella-zoster virus reactivation. Acyclovir prophylaxis virtually eliminates the risk of zoster in patients receiving bortezomib [103,104]. The currently available shingles vaccine is not suitable for immunocompromised patients as it is a live vaccine. The Advisory Committee on Immunization Practices (ACIP) recommendations [105] advocate the use of the 13-valent prior to the 23-valent pneumococcal vaccine among immunocompromised adults. The flu vaccine is also recommended on a yearly basis.

Nutrition

The Prognostic Inflammatory and Nutritional Index (PINI) is a simple scoring system evaluating nutritional states routinely used in geriatric assessments. In a retrospective analysis, among 231 patients with myeloma (including 112 patients aged over 65) a PINI score ≥4 was associated with a shorter survival regardless of the cytogenetic profile [106]. This should prompt early intervention studies to improve outcomes in this population.