Prognostic factor analyses of myeloma survival with intergroup trial S9321 (INT 0141): examining whether different variables govern different time segments of survival

Multiple myeloma (MM) survival plots usually display steeper initial and shallower subsequent slopes reflecting differences in disease biology and likely prognostic factors (PF). S9321 trial was selected to determine PF operative at baseline and subsequent 3, 4, 5, and 7-year landmarks (LM-0, LM-3, LM-4, LM-5, and LM-7). With a median follow-up of 8.2 years, survival was similar in transplant and standard therapy arms, justifying data pooling. Median survival for 775 eligible patients is 48 months. According to proportional hazards models, seven of 12 investigated baseline variables retained independent significance for LM-0, of which only two (beta-2-microglobulin and age) extended out to LM-7; the remaining five comprised features of disease aggressiveness (lactate dehydrogenase, calcium, platelet count, C-reactive protein) and host co-morbidity (performance status). Our observations of LM dependency of PF can be exploited toward advancing myeloma therapy by stratifying patients according to whether early or late portions of the survival history are being targeted.