Zoledronic acid as compared with observation in Multiple Myeloma patients at biochemical relapse: results of the randomized AZABACHE Spanish trial
García-Sanz R(1), Oriol A(2), Moreno MJ(3), de la Rubia J(4), Payer AR(5), Hernández MT(6), Palomera L(7), Teruel AI(8), Blanchard MJ(9), Gironella M(10), Ribas P(11), Bargay J(12), Abellá E(13), Granell M(14), Ocio EM(15), Ribera JM(16), San Miguel JF(17), Mateos MV(15) (1) Hospital Universitario de Salamanca, IBSAL, IBMCC USAL CSIC;
(2) ICO, Hospital Germans Trias i Pujol, Fundacio Josep Carreras;
(3) Hospital Morales Meseguer;
(4) Hospital Universitario La Fe and Universidad Catolica de Valencia;
(5) Hospital Universitario Central de Asturias;
(6) Hospital Universitario de Canarias;
(7) Hospital Lozano Blesa de Zaragoza;
(8) Hospital Clinico Universitario de Valencia;
(9) Hospital Universitario Ramon y Cajal de Madrid;
(10) Hospital Universitario Vall de Hebron de Barcelona;
(11) Hospital Universitario Dr. Peset de Valencia;
(12) Hospital Son Llatzer de Palma de Mallorca;
(13) Hospital del Mar de Barcelona;
(14) Hospital de la Santa Creu i Sant Pau de Barcelona;
(15) Hospital Universitario de Salamanca-IBSAL, IBMCC (USAL-CSIC);
(16) ICO - Hospital Germans Trias i Pujol, Fundacio Josep Carreras;
(17) Clinica Universidad Navarra-CIMA.
This study analyzed the anti-myeloma effect of zoledronic acid monotherapy by investigating patients at asymptomatic biochemical relapse. 100 patients were randomized to receive either zoledronic acid (4 mg iv/4 wk, 12 doses) (n=51) or not (n=49). Experimental and control groups were well balanced for disease and prognostic features.
Zoledronate did not show antitumor effect according to M-component outcome. However, there were fewer symptomatic progressions in the experimental (n=34) than in control groups (n=41, P=0.05) resulting in a median time to symptoms of 16 vs. 10 months (P=0.161). Median time to next therapy was also slightly longer for treated vs. no treated groups (13.4 vs. 10.1 months), without statistically significant differences (P=0.360).
The relapsing pattern was different for treated vs. control patients: progressive bone disease (8 vs. 20), anemia (24 vs. 18), renal dysfunction (1 vs. 2), and plasmacytomas (1 vs. 1, respectively). This concurred with fewer skeletal related events in the experimental (N=2) vs. control (N=14) groups, with a projected 4-year event proportion of 6% vs. 40% (P< 0.001).
In summary, zoledronic acid monotherapy does not show antitumor effect in myeloma biochemical relapses but reduces the risk of progression with symptomatic bone disease and skeletal complications. ClinicalTrials.gov: NCT01087008.
CITATION Haematologica. 2015 Jun 11. pii: haematol.2015.128439