Survival analyses. (A) Time to treatment registration in 59 previously untreated patients who did not require therapy at initial registration. At 9 years, only 21% required initiation of therapy. (B) Survival outcomes from registration to treatment. Median durations of overall and event-free survival are 6.8 years and 3.0 years, respectively; 4 patients who were ineligible for the treatment step are excluded. (C) Overall survival according to the number of risk factors present at treatment registration. Risk factors analyzed were as follows: age 70 years or older, previous nonprotocol therapy, B2M 3 mg/L or greater and LDH more than or equal to the upper limit of normal. Three distinct groups with marked different outcomes could be distinguished. The 98 patients with no more than 1 risk factor had an 8-year survival estimate of 55%, compared with 33% among the 51 with 2 risk factors (P < .001), whereas the 20 patients with more than 2 risk factors had an 8-year survival estimate of only 5% (P < .003). (D) Overall survival according to the ISSWM-defined risk groups and serum LDH levels. ISSWM risk groups were defined as noted. Low risk: age younger than 65 years and, at most, one of the following: hemoglobin less than 11.5 g/dL, platelets less than 100 × 109/L, B2M greater than 3 mg/L, M-protein component greater than 7.0 g/dL; high risk: at least 3 of the following: age older than 65 years, hemoglobin less than 11.5 g/dL, platelets less than 100 × 109/L, B2M greater than 3 mg/L, M-protein component greater than 7.0 g/dL; intermediate risk: patients with 2 of the following: age older than 65 years, Hb less than 11.5 g/dL, platelets less than 100 × 109/L, B2M greater than 3 mg/L, M-protein component greater than 7.0 g/dL. Patients older than 65 years of age not fulfilling high-risk criteria were classified as intermediate risk. Survival was analyzed for cohorts with low-intermediate ISSWM risk (“not high”) or high ISSWM risk (“high”) on the basis of either normal or elevated serum LDH. P values: not high risk: low versus high LDH: P = .044; high risk: low versus high LDH: P = .108.