Recommendations in parentheses are in the absence of phase 3 comparative studies in the era of novel agents.

*There are no phase 3 studies comparing recent induction regimens including RVD, VCD, and VTD. RVD and VCD appear to generate deeper responses than 2-agent induction regimens. Early reports suggest that very recent regimens may generate even deeper responses, but this remains to be studied in phase 3 trials. Specific treatment recommendations: for renal failure patients: bortezomib and dexamethasone; for del(13), t(4;14)cytogenetic abnormality: bortezomib-containing regimens. GEP-70 positive, del(17p), del(1p), +1q, and plasma cell leukemia patients are very high risk and are candidates for trials examining novel agents or allogeneic HSCT in younger patients. Bortezomib is now given subcutaneously without apparent loss of efficacy and with diminished toxicity (neuropathy).⁵⁷ 

†Single autologous HSCT is recommended. Tandem autologous HSCT has been shown to improve response in ≤ VGPR patients before the use of proteasome inhibitors and immunomodulatory drugs. Studies are ongoing to examine the role of early versus delayed autologous HSCT and tandem autologous HSCT after newer induction regimens.

‡There are no phase 3 studies examining R and RVD consolidation. Studies are ongoing examining RVD consolidation. VTD and V have been shown to improve PFS.

§Thalidomide improves PFS and OS in some studies, does not appear to be effective in high-risk disease, and is not as well tolerated long term. VT in one study improved PFS but not in high-risk disease. Two years of bortezomib maintenance was not significantly different from thalidomide in standard-risk disease. Lenalidomide maintenance until progression improved PFS in standard-risk patients. Lenalidomide and bortezomib have been shown to improve outcome in some patients with high-risk disease and in all responding patients (in CR and not in CR).

‖Very-high-risk patients with plasma cell leukemia; t(14;16), del(17p), del(1p), and +1q cytogenetic abnormalities; or GEP 70 positivity: RVD in maintenance doses should be considered for these patients because they do not do well with single-agent maintenance.