Fixed duration vs continuous therapy in multiple myeloma

Abstract

The introduction of new drugs with less severe toxicity profiles than those of conventional antimyeloma agents allowed the evaluation of continuous therapy compared with fixed duration therapy. In transplant-eligible patients, consolidation therapy with bortezomib or bortezomib-based regimens showed significant progression-free survival (PFS) benefit in cytogenetic standard-risk patients and to a lesser extent, high-risk patients. Continuous therapy with lenalidomide maintenance treatment after autologous stem cell transplantation resulted in a significant survival gain. In transplant noneligible patients, continuous lenalidomide-dexamethasone therapy improved survival over fixed duration melphalan-prednisone-thalidomide. The concept of prolonged treatment in elderly patients is supported by some other studies, but most of them revealed a gain in PFS only. Young patients with unfavorable prognosis show a greater willingness to accept long-term treatment, whereas the readiness to undergo such treatments and the benefits therefrom decline with increasing age and decreasing fitness, rendering fixed duration therapy a suitable option in elderly frail patients.

Figure 1.

Patient and disease characteristics, their willingness to accept long-term treatment, and expected outcome. High-risk: t(4;14), t(14;16), t(14;20) del 17p, nonhyperdiploidy, and ampl1q21. Yes+ denotes benefit, and Yes+++ denotes greater benefit.

Figure 2.

Treatment options for consolidation and prolonged or continuous therapy based on results of randomized trials. KRd has not been tested in randomized comparisons. Improved PFS was seen in (1) 3 of 3, (2) 1 of 2, (3) 1 of 1, (4) 1 of 4, (5) 4 of 4, and (6) 6 of 6 randomized trials. TXT, treatment; BTZ, bortezomib; VCD, Velcade-cyclophosphamide-dexamethasone; THAL, thalidomide; REV, Revlimid; DEX, dexamethasone.