The prognostic role of 1q21 gain/amplification in newly diagnosed multiple myeloma: The faster, the worse.

Abstract

The prognostic value of additional copies of chromosome 1q (1q gain/amplification [amp]) in multiple myeloma (MM) remains controversial. In the meantime, the kinetics of the response to MM therapy has long been an area of debate. Few studies have pointed out the relationship of response kinetics with cytogenetic abnormalities (CAs) in MM. The authors retrospectively analyzed the data of 1068 real-world newly diagnosed MM patients from a Chinese national medical center. Overall, 405 (51.9%) patients had 1q gain/amp, with aggressive clinical characteristics and significant inferior survival. The variation in copy number (CN) of 1q (CN=3 or CN>3) had no significant impact on the survival of MM patients with 1q abnormalities. No difference was found in the outcome of 1q gain/amp patients treated with doublet or triplet regimens. Upfront autologous stem cell transplantation could eliminate the adverse prognostic effect of 1q gain but not 1q amp. The duration from diagnosis to the first time achieving very good partial response (VGPR) or better was significantly shorter in patients with 1q gain/amp (77days vs. 100days, p=.001). Finally, multifactor regression analysis was performed to construct a new risk stratification model in MM patients with 1q gain/amp, which was validated in the Multiple Myeloma Research Foundation CoMMpass study cohort and worked better than the Revised International Staging System and Second Revision of the International Staging System (Harrell's concordance index: 0.631 vs. 0.598 and 0.537). In the setting of novel therapy, 1q gain/amp still acts as an independent adverse prognostic factor. Patients with 1q gain/amp achieved VGPR rapidly but had inferior survival.