Effect of Disease Stage and Time Since Diagnosis on Time to Progression for Pegylated Liposomal Doxorubicin + Bortezomib vs Bortezomib Alone in Relapsed or Refractory Multiple Myeloma.

A recent report of a phase III randomized trial with pegylated liposomal doxorubicin (PLD)+bortezomib vs. bortezomib alone in relapsed or refractory multiple myeloma (RRMM) demonstrated improved time to progression (TTP) with PLD+bortezomib (Orlowski, JCO 2007). The present post-hoc analyses evaluated the efficacy of PLD+bortezomib according to International Staging System (ISS) disease stage, and time since initial myeloma diagnosis (TSD). Patients with ≥1 prior therapy were randomized to receive PLD at 30 mg/m² on day 4 and bortezomib at 1.3 mg/m² on days 1, 4, 8, and 11, or bortezomib alone for up to eight 21-day cycles, or at least 2 cycles beyond CR, or optimal response unless disease progression or unacceptable toxicities occurred. The improved TTP reported previously with PLD+bortezomib over bortezomib alone in the total study population was also observed in the higher risk groups based on disease stage (ISS 2 & 3; Table). TTP was also significantly longer with PLD+bortezomib vs. bortezomib for TSD >2 yrs despite more protracted disease. The therapeutic advantage of prolonged TTP with the PLD+bortezomib combination was maintained consistently across subgroups (heterogeneity tests: ISS 1 vs. 2 vs. 3, p=0.407; TSD ≤2 yrs. vs. >2 yrs., p=0.946). Incidence of grade 3/4 neuropathies was low (<10%) in the two treatment arms in all subgroups. PLD-related hand-foot syndrome was also <10% in all PLD+bortezomib subgroups. Despite high-grade disease or protracted disease history, the PLD+bortezomib combination shows significantly improved TTP as compared to bortezomib alone. Also, the combination therapy was well-tolerated.

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