Abstract:
Objective To evaluate the prognostic value and limitations of the revised international staging system (R-ISS) in newly diagnosed multiple myeloma (MM).
Methods The clinical data of 568 patients newly diagnosed with MM in Institute of Hematology & Blood Diseases Hospital from June 2002 to November 2017 were retrospectively analyzed. All patients received induction therapy with bortezomib or thalidomide/lenalidomide for at least 4 cycles. The prognostic significance of R-ISS was analyzed by comparing it to the international staging system (ISS). Considering the great heterogeneity between MM patients in R-ISS phase Ⅱ, we assigned the patients in this phase into four groups: the first group was characterized by elevated lactate dehydrogenase (LDH) levels or high-risk genetic abnormalities in ISS stage Ⅰ; the second group patients did not have elevated LDH levels and high-risk genetic abnormalities in ISS stage Ⅱ; the third group patients had elevated LDH levels or high-risk genetic abnormalities in ISS stage Ⅱ; and the fourth group patients had no LDH or high-risk genetic abnormalities in ISS stage Ⅲ. Survival analysis was performed among these groups.
Results Among the 568 newly diagnosed MM patients, 347 were male and 221 were female, with a median age of 56 (25-83) years. The median follow-up period was 33 (4-203) months. Under the R-ISS, 59 (12%), 310 (62%), and 130 (26%) patients had stage Ⅰ, Ⅱ, and Ⅲ disease, respectively. The median overall survival (mOS) in the corresponding patients were 142, 86, and 48 months, respectively (χ2=29.588, P < 0.001). Under the ISS, 106 (19%), 210 (37%), and 252 (44%) patients had stage Ⅰ, Ⅱ, and Ⅲ disease, respectively. The median OS in the corresponding patients were 142, 71, and 63 months, respectively (χ2=22.099, P < 0.001). The hazard ratio (HR) of Ⅲ vs. Ⅰ, Ⅱ vs. Ⅰ of ISS system were 2.903 (P < 0.001) and 1.985 (P=0.005). The HR of Ⅲ vs. Ⅰ, Ⅱ vs. Ⅰ of R-ISS system were 5.441 (P < 0.001) and 2.844 (P=0.003). The median OS of the four groups in R-ISS Ⅱ were 126, 83, 49 (95% CI: 33-65), and 65 (95% CI: 44-86) months (P=0.131), respectively. In general, there were no significant differences in OS between the four groups; however, there were significant differences between groups 2 and 3 (χ2=4.916, P=0.027).
Conclusions R-ISS is better than ISS for differentiating the prognosis of MM patients. The R-ISS has a strong prognostic value for OS in patients with extramedullary infiltration or 1q21 amplification, for those in different age groups (age ≥65 years and age < 65 years), for those with different treatment schemes (bortezomib and thalidomide treatment groups), and for those with different chromosome multiples (low diploid and non-low diploid). However, the survival differences between the R-ISS stage Ⅱ patients still need clinical concern.