Low Incidence of Complete Remission but Comparable Event-Free Survival(EFS) and Overall Survival (OS) with a History of Prior Monoclonal Gammopathy of Undetermined Significance (MGUS) or Smoldering Myeloma (SMM) among Patients Receiving Total Therapy 2 (TT 2).

Abstract Symptomatic/progressive MM sometimes develops on the background of MGUS or progresses through a smoldering MM phase (SMM); other patients may have initially a solitary plasmacytoma of bone (SPC). This study examines the survival implications of pre-existing conditions such as MGUS (n=22), SMM (n=22) or SPC (n=20) among 668 enrolled in TT 2. TT 2 consists of intensive remission induction, melphalan-based tandem autotransplants; consolidation chemotherapy and interferon maintenance. 2 yr estimates of CR/near-CR (only IFE-positive) were similar in de novo MM (44%/67%) and in those with preceding SPC (46%/67%); both were higher than in case of preceeding SMM (24%/38%) or MGUS (17%/49%) (p=.009/p=.007). According to multivariate analysis, the time to CR was shorter in the presence of LDH > 190 U/L (HR 1.33, p=.003) and IgA isotype (HR 1.3, p=.08) but longer in the case of preceeding MGUS or SMM (HR 0.44, p=.02). Kaplan Meier plots of EFS and OS were similar for de novo MM and patients with the 3 precursor conditions. We conclude: (1) the low incidence of stringently defined CR among patients with preceeding MGUS or SMM does not negatively impact EFS or OS after initiation of therapy for symptomatic/progressive MM; (2) this lower incidence of CR may reflect the re-establishment of a stable precursor state due to the high level of drug resistance of these low proliferative activity conditions; (3) patients with de novo MM not achieving CR but having a prolonged EFS/OS may be those with a clinically unrecognized precursor condition; (4) measurements other than M protein-reduction must be identified to better assess minimal residual disease. Figure Figure