The impact of frontline risk-adapted strategy on the overall survival of patients with newly diagnosed multiple myeloma: an analysis of the Singapore multiple myeloma study group.
INTRODUCTION
Risk stratification is vital for prognostication and informing treatment decisions in multiple myeloma (MM). We study the prognostic values of the International Staging System (ISS) and underlying cytogenetics in the bortezomib era and assess the impacts of an upfront risk-adapted approach in the treatment of MM.


METHODS
We compare the overall survival (OS) of 221 patients with MM diagnosed from 2006 to 2009 (era 2) where upfront bortezomib combination was approved for high-risk MM with the OS of 262 patients diagnosed from 2000 to 2005 (era 1) where bortezomib could only be administered at relapse. High-risk MM is defined by the presence of ISS III disease with renal impairment or adverse cytogenetics.


RESULTS
Baseline characteristics were comparable between the 2 eras. At median follow-up of 20 months, 0% and 26% of patients had received frontline bortezomib in eras 1 and 2, respectively. The median OS were 4.2 yrs and not reached for eras 1 and 2, respectively (P = 0.03). On multivariate analysis stratified by era, the most significant prognostic factor shifts from cytogenetics in era 1 to the quality of response in era 2.


CONCLUSION
Frontline use of bortezomib in a risk-adapted manner may avert early mortality and is better able to overcome adverse risks compared to its sequential use.