Complete response in myeloma extends survival without, but not with history of prior monoclonal gammopathy of undetermined significance or smouldering disease

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Abstract
Summary: Complete response (CR) is still considered an important surrogate marker for outcome in multiple myeloma (MM). Long‐term survival after transplantation, however, has been observed in a substantial proportion of patients who never achieved CR. The tandem transplant trial, Total Therapy 2, enrolled 668 patients, who were randomised up‐front to thalidomide (THAL) or no THAL; 56 patients were identified as having had, for at least 6 months prior to initiation of therapy, monoclonal gammopathy of undetermined significance (MGUS,n = 21), smouldering MM (SMM,n = 22) or solitary plasmacytoma of bone (SPC,n = 13). The clinical characteristics and outcomes of patients with such ‘evolved’ MM (E‐MM) and of those with ‘unknown’ prior history (U‐MM) were compared. Fewer patients with MGUS/SMM‐E‐MM had anaemia or renal failure; CR was lower (22% vs. 48%) but 4‐year estimates of event‐free survival (54% vs. 56% with U‐MM) and overall survival (65% vs. 70% with U‐MM) were similar to those with SPC‐E‐MM or U‐MM. In the latter group, achieving CR was associated with prolonged survival. In comparison with U‐MM, E‐MM evolved from MGUS/SMM was associated with lower CR rate without adversely affecting survival. In contrast, CR was an independent favourable feature for survival in U‐MM.