Multiple Myeloma with Prior Precursor Disease Shows Better Outcome
Authors: Ríos-Tamayo Rafael , Sáinz Pérez Juan , Jurado Manuel , Puerta Puerta Jose Manuel , González Sierra Pedro Antonio , Romero Aguilar Antonio , Lopez Fernandez Elisa , Moratalla Lopez Lucia , García de Veas Silva José Luís , Rodríguez Ruiz Teresa , Jiménez Moleón José Juan , Sánchez Pérez María José 
Published: October 2019

Abstract
Introduction
All symptomatic multiple myeloma (MM) patients are virtually preceded by a precursor disease (PD). However, the PD is rarely known at the time of diagnosis of MM. Several PD can progress to MM: monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM) and solitary plasmacytoma (SP). Sigurdardottir et al have recently demonstrated that only 2.7% in a series of 14798 MM patients had prior knowledge of MGUS. This group had better overall survival (OS), stressing the importance of clinical follow-up in MGUS and suggesting that earlier treatment of MM leads to better OS. Nonetheless, we have recently shown that diagnostic delay in MM have a paradoxical effect on OS. Furthermore, little is known about the outcome of MM with prior knowledge of other PD.
Methods
All symptomatic MM patients diagnosed between January 1993 and July 2015 in our MM population-based registry, excluding palliative patients, were selected. Information about any prior PD was checked, as well as baseline common prognostic factors such as age, sex, lactate dehydrogenase (LDH), creatinine (Cr), International Staging System (ISS), high-risk FISH, and diagnostic delay. Comparisons among groups were made with the χ2-testfor categorical and t-test for quantitative variables. OS was estimated in months (m) by the Kaplan-Meier method in patients with or without specific PD or any PD as a whole. Log-rank test was used to compare curves. A Cox proportional hazard model was used to assess the simultaneous impact on survival of prior PD and other predictors.
Results
473 MM patients fulfilled the inclusion criteria. 383 of them (81%) had available data concerning prior PD. There were 233 men and 240 women (50.7%), median age 67 years (12-87). 19 patients (5%), 10 (2.6%) and 5 (1.3%) had prior MGUS, SP and SMM, respectively. The group without prior PD had significantly higher values of serum Cr (2.09 vs 1.09 mg/dL, p<0.001), LDH (317.3 vs 256.2 U/L, p=0.09), ISS3 (49.6% vs 22.2, p=0.02), but less delay (5.6 vs 10.9 m, p=0.002). Median OS of patients with prior MGUS was 87.7 m (57.1-118.2) vs 34.4 (27.8-41.1)(p=0.112), with prior SP 88 m (46.9-129) vs 34.9 (28.4-41.5)(p=0.101) and prior SMM 104.1 m vs 36 (29.9-42.1)(p=0.102). Median OS of any PD (Fig 1) was 88 m (82.6-93.3) vs 32.7 (26.2-39.2)(p=0.006). In the multivariate model, age, LDH and Cr are significantly associated with survival. The presence of prior PD, when adjusting for these factors, is also significantly associated with survival, acting as a protective factor. When ISS is added to the model, prior PD remains only marginally significant.
Conclusion
Prior knowledge of PD is infrequent at the moment of MM diagnosis. MM with any previously documented PD seems to have better outcome. The reason for this finding is not an earlier diagnosis, but rather a better prognostic profile. However, we cannot rule out other underlying biological mechanisms. More and larger studies are warranted to confirm our results.

Disclosures
No relevant conflicts of interest to declare.