Prolonged use of Zoledronic Acid reduces skeletal events but does not improve OS

Zoledronic Acid (ZA) is a bisphosphonate (BP) that inhibits osteoclast-mediated osteolysis, thereby minimizing skeletal-related events (SREs), for which MM patients are at high risk. The precursor to SREs are bone lesions, and it is the occurrence of these that often lead MM patients towards a diagnosis. BP therapy is administered to MM patients, regardless of whether bone lesions are detected and ZA is the preferred choice, with a recommended treatment duration of 2 years. However, with advances in both treatment and patient care, overall survival is now longer, and so the benefits of lengthening the treatment window for ZA is a valid question. This was addressed in a recent study published by Agustin Avilès and colleagues from the Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico, and published in Clinical Lymphoma, Myeloma and Leukemia in April 2017.

Key Findings:

• Single center study, 170 patients (with untreated, symptomatic MM) enrolled from January 2009 to December 2014
• Of the 170 patients (pts) enrolled, 84 received ZA for 4 years and 86 received ZA for 2 years
• Primary endpoint = progression-free survival (PFS), overall survival (OS), and safety
• All pts received the same induction therapy and stem-cell transplantation
• Median follow-up = 40.4 months
• Analysis of 5-year actuarial curves:
  • Pts on ZA (both groups): PFS = 75% (95% CI, 64-82) and OS = 68% (95% CI, 60%-76%)
  • Control group: PFS =72% (95% CI, 62-78) and OS = 68% (95% CI, 62-75)
  • Pts on ZA for 4 years: PFS = 75% and OS = 68%
  • Pts on ZA for 2 years: PFS = 72% and OS 68%
  • No statistically significant differences between the control and treatment groups, or between the 2- and 4- year treatment groups
• Skeletal-Related Events: ZA for 4 years = 21% (n=18) vs ZA for 2 years = 43% (n=37) (p=0.01)

In conclusion, prolonged use of ZA (4 years) improved the outcome for patients with regards to fewer SREs, but did not improve OS. Osteocronosis of the jaw, usually associated with ZA, was not observed in either group. Therefore, prolonged ZA treatment may benefit patients in terms of improved quality of life, although the small patient number in this study must be noted as a limitation.