Are bisphosphonates (BPs) indicated in patients with multiple myeloma and lytic lesions?

Bisphosphonates in Multiple Myeloma with Lytic Lesions

Yes, bisphosphonates are strongly indicated for patients with multiple myeloma who have lytic bone lesions on plain radiographs or imaging. This is a firm, evidence-based recommendation supported by multiple high-quality guidelines and FDA approval 1, 2.

Primary Recommendation

For multiple myeloma patients with lytic bone destruction on plain radiographs, initiate bisphosphonate therapy immediately upon diagnosis of bone disease 1. The approved options are:

• Intravenous pamidronate 90 mg delivered over at least 2 hours every 3-4 weeks 1
• Intravenous zoledronic acid 4 mg delivered over at least 15 minutes every 3-4 weeks 1, 2
• Oral or intravenous clodronate (approved worldwide except in the United States) 1

Evidence Supporting Use

The evidence base is robust. Bisphosphonates reduce skeletal-related events (SREs) by 30-40% in multiple myeloma patients with lytic disease 1. Specifically:

• Pamidronate reduces the mean number of SREs from 2.2 per year to 1.3 per year (P = 0.008) 1
• Median time to first skeletal event increases from 10 months with placebo to 21 months with pamidronate (P = 0.001) 1
• At 12 months, 28% of pamidronate-treated patients versus 44% of placebo patients experienced an SRE (P = 0.001) 1

Choice of Agent: Important Nuance

While both pamidronate and zoledronic acid are effective, pamidronate may be preferred initially due to a significantly lower risk of osteonecrosis of the jaw (ONJ) 1. The ASCO guideline specifically notes a 9.5-fold greater risk of ONJ with zoledronic acid compared to pamidronate 1. However, zoledronic acid offers the convenience of a 15-minute infusion versus 2-4 hours for pamidronate 1, 2.

Duration of Therapy

Administer bisphosphonates monthly for at least 2 years 1. After this period:

• After 1 year: Consider continuing at physician's discretion, particularly if disease is below very good partial response (VGPR) or if active bone disease persists 1
• After 2 years: Seriously consider stopping in patients with responsive or stable disease and no active bone disease 1
• Resume therapy if skeletal-related events develop upon relapse 1

Essential Monitoring and Safety Measures

Renal Function

Monitor serum creatinine or creatinine clearance before each dose 1, 2. Bisphosphonates carry significant renal toxicity risk, particularly in patients with pre-existing renal impairment 2. Do not use doses greater than 4 mg of zoledronic acid 2.

Osteonecrosis of the Jaw Prevention

Perform preventive dental examination before starting bisphosphonates 2. The incidence of ONJ in myeloma patients treated with bisphosphonates is approximately 4.6%, with higher rates associated with zoledronic acid 3. Avoid invasive dental procedures while on therapy 2. If ONJ develops, discontinue bisphosphonates until healing occurs, then restart if disease progresses 1.

Calcium and Vitamin D Supplementation

Coadminister oral calcium supplements of 500 mg and vitamin D 400 international units daily 2. Correct hypocalcemia before initiating therapy 2, as bisphosphonates can cause severe or life-threatening hypocalcemia 2.

Hydration

Adequately rehydrate patients with hypercalcemia of malignancy prior to administration and monitor electrolytes during treatment 2.

Common Pitfalls to Avoid

• Do not delay bisphosphonate initiation: Start as soon as lytic disease is diagnosed on plain radiographs 1
• Do not stop bisphosphonates when bone disease progresses: Unlike antineoplastic drugs, bisphosphonates provide supportive care and should continue despite progression 4, 5
• Do not use in patients with severe renal impairment without dose adjustment: Treatment is not recommended in severe renal impairment 2
• Do not perform dental extractions while on therapy without careful consideration: All 9 patients in one case series who developed ONJ had undergone tooth extraction while taking bisphosphonates 6

Administration Details

Administer through a separate vented infusion line 2. Do not allow contact with calcium or divalent cation-containing solutions 2. For pamidronate, use a 2-4 hour infusion time 1; for zoledronic acid, use at least 15 minutes 2.