Zoledronic acid did not have any antitumor effect in asymptomatic multiple myeloma patients in relapse, but did delay symptomatic progression and bone disease.
Zoledronic acid did not have any antitumor effect compared with no treatment in patients with multiple myeloma and asymptomatic biochemical relapse, but it did delay symptomatic progression and bone disease, according to the results of the AZABACHE Spanish trial published in Haematologica.
Based on these results, study researchers led by RamÃ³n GarcÃa-Sanz, MD, PhD, of the Hospital Universitario de Salamanca-IBSAL in Salamanca, Spain, concluded that zoledronic acid “should be considered as a new standard of care for this group of patients.”
The AZABACHE trial included 100 patients with multiple myeloma in biochemical relapse and randomly assigned them to zoledronic acid 4 mg every 4 weeks for 12 doses or to no treatment (control group).
The median follow-up of the surviving patients was 38 months. The median time to next therapy was 10.9 months for the entire study population. The researchers observed no difference in myeloma response between patients assigned zoledronic acid and those in the control group.
Patients assigned to zoledronic acid did have improvement in symptom control; 67% of patients in the intervention group progressed to symptomatic disease compared with 83% in the control group (P = .05). However, the researchers noted, “this only partially translated into differences in the survival curves.”
Time to next therapy was numerically, but not significantly, longer in patients assigned zoledronic acid (13.4 vs 10.1 months; P = .36).
“The pattern of the clinical relapse showed relevant differences according to the group of therapy,” the researchers noted. Among those who progressed in the control group, 20 patients developed more advanced bone disease (hypercalcemia in 2 patients, spinal cord compressions in 3 patients, and new bone lesions in 15 patients). Other signs of progression in this group included plasmacytoma in 1 patient, renal dysfunction in 2 patients, and anemia in 18 patients.
Progressions in the zoledronic acid group included renal dysfunction in 1 patient, extramedullary disease in 1 patient, new bone lesions in 8 patients, and anemia in 24 patients.
The use of zoledronic acid was associated with significantly fewer skeletal-related events than the control group (only two of the skeletal-related events that occurred were in patients in the intervention arm). The 4-year risk for skeletal-related events was 6% for zoledronic acid compared with 40% for the control group (P < .001).
“The present randomized trial, do not support a direct antitumor effect for intravenous zoledronic acid when administered as single therapy in myeloma patients at biochemical relapse, since no reduction in M-component or prolongation in time to next therapy was observed,” the researchers wrote. “However, upon considering that clinical progressions in the control group were mainly due to bone disease, we may counter-argue in favor of the use of zoledronic acid in patients at biochemical relapse.”