What remains an argument at this time is the concept that sequential therapy is associated with lower toxicity than with combination therapies, especially when curing the disease is not the primary goal, just as in the case of metastatic breast cancer where sequential therapies are favored over combination therapies. Sequential therapy may find a niche in the maintenance setting where the goal is prolonged therapies with lower toxicity. As reported by a Phase II feasibility study, sequential bortezomib and dexamethasone for six cycles followed by TD maintenance therapy until progression after single peripheral ASCT in 45 patients with MM demonstrated that a prolonged sequential weekly regimen is feasible and well tolerated, and upgraded post-ASCT CR responses by 33% with maintenance therapy with no increase in grade 3 or 4 peripheral neuropathy. Although it may be interesting to note that this approach might hold well for low- or standard-risk patients, the efficacy of such sequential maintenance therapies in high-risk patients is still uncertain. There is clear early evidence for combination therapies with RVD maintenance therapy for high-risk patients based on the same preclinical observations already discussed. From current observations, combination therapies based on preclinical justification in the setting of induction therapy and sequential therapies in the maintenance setting seem to be optimal.
Expert Rev Hematol. 2012;5(5):533-545. © 2012 Expert Reviews Ltd.