These side effects lead to a reduction in quality-of-life parameters and premature discontinuation even when low doses are used. Several phase 2 and 3 studies have evaluated the use of novel agents as … Until further information is available, the selection of the preferred approach will likely depend on issues of toxicity and patient/physician preference. CHICAGO-Maintenance therapy with lenalidomide after autologous stem cell transplantation significantly prolonged survival in patients with multiple myeloma, according to the results of a meta-analysis presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract The data, presented by Philip L. McCarthy, MD, of Roswell Park Cancer Institute in Buffalo, New York, showed that maintenance lenalidomide resulted in an estimated 2.5-year improvement in median overall survival, meaning that “lenalidomide is feasible for the long-term disease control after autologous stem cell transplant.”According to McCarthy, autologous transplant is the standard of care for fit patients with newly diagnosed multiple myeloma; however, most patients who undergo transplant, even those who achieve a complete response, will eventually relapse or progress. However, it can still be difficult to isolate the impact of novel induction regimens on the posttransplantation outcome, particularly OS, because many trials also include maintenance and/or consolidation measures post-ASCT. To date, the best reported results with respect to PFS have used novel agents in induction followed by lenalidomide as maintenance after ASCT, and the ongoing CTN trial will help to determine the contribution of a second ASCT or consolidation therapy to lenalidomide maintenance. In addition, in the past, the conventional approach has been to use 3 or 4 cycles of induction and then proceed to stem cell collection and ASCT. These rates are comparable to or higher than those observed after ASCT in the era before novel agents.Several large phase 3 trials comparing novel combinations with older induction regimens followed by ASCT in all patients have now been reported. Specifically, after several cycles, patients have the option of undergoing elective ASCT or remaining on all or some of the drugs in induction, a design that introduces considerable bias when assessing the long-term effect of these regimens. He received no maintenance therapy, and for the last 8 years has had no treatment whatsoever. The next section focuses on the use of newer measures before and after the actual transplantation procedure, with an emphasis on the results of phase 3 studies.Because numerous studies have noted that patients achieving CR, nCR, and/or VGPR after transplantation have longer remissions and survival times than those with lesser responses, it has been hypothesized that the achievement of such high-grade responses before ASCT would increase the number of patients in this favorable state after the procedure and would in turn confer a better PFS and OS. These newer studies may report the response rates after 4 cycles, but the depth of response often continues to improve with subsequent cycles, so that the optimal duration of administration before ASCT is uncertain. Starting with chemotherapy in 1975, to interferon in 1998, to novel agents recently, a multitude of agents have been explored in patients with multiple myeloma. The idea of maintenance therapy in multiple myeloma is not new. The results of this trial contrast with concurrent trials investigating post-transplantation approaches in myeloma. Two cycles of lenalidomide (25 mg daily) improved …

Earlier ASCT studies used less potent agents such as corticosteroids or IFN-α with variable results and, particularly with IFN-α, toxicity concerns. Currently, the superiority of any one particular post-ASCT strategy using novel agents has not been established with absolute certainty, although the phase 3 trials of lenalidomide maintenance compared with placebo have demonstrated the longest PFS after ASCT reported to date: > 3.5 years. In practical terms, patients can usually tolerate the drug < 1 or 2 years before side effects become prohibitive.More recently, lenalidomide maintenance therapy has been studied, and 2 randomized trials comparing low doses of lenalidomide (10-15 mg/d) with placebo after ASCT have completed accrual: the CALGB-100104 trial in North America and the IFM 2005-02 study in France.An unexpected finding from the lenalidomide maintenance trials was a modest increase in the incidence of secondary cancers, including secondary myelodysplastic syndromes (MDS) and/or acute myelogenous leukemia (AML): ∼ 6.5% in both studies compared with 1.6%-2.6% in the placebo groups for all tumor types.The risk of secondary cancers when novel agents other than lenalidomide are used for maintenance after ASCT has not been rigorously evaluated, but appears to be low. For example, the NCIC trial reported only 1 fatal secondary cancer in the thalidomide plus prednisone maintenance arm (0.6%) versus 2 in the observation arm (1.2%).The use of consolidation therapy after ASCT has been evaluated in 3 recent phase 3 trials. • Elotuzumab may provide additional efficacy to standard therapy post-transplant. This can include their administration before, during, and after the transplantation procedure. One of the major efforts to improve the results of intensive therapy and autologous stem cell transplantation (ASCT) in multiple myeloma involves the integration of novel agents into the transplantation sequence. However, the definition of consolidation is not standardized in myeloma, and the difference between consolidation and maintenance is not always clear. Previous studies have shown that lenalidomide maintenance after transplant reduced the risk for disease progression or death by about 50%, but none of these studies were designed to evaluate overall survival as a primary outcome.With this meta-analysis, McCarthy and colleagues evaluated whether post-transplant maintenance lenalidomide had any effect on overall survival. Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma: Results of the BMT CTN 0702 Trial.