Long-Term Survival in Patients Receiving Conventional Therapy for Newly Diagnosed Multiple Myeloma; Results from United Kingdom Medical Research Council Trials 1980–1997.
Authors: Augustson Bradley M. , Begum Gulnaz , Morgan Gareth J. , Child J. Anthony , Barth Nicola J. , Dunn Janet A. , Drayson Mark T. 
Published: October 2019

Abstract
Introduction: With conventional therapy, the median survival for patients following diagnosis of multiple myeloma (MM) is 31 months. Prior to 1985 2–4% of patients survived up to 10 years, subsequently this figure has improved to around 10%. We have analysed the United Kingdom Medical Research Council (MRC) trial records to identify the proportion, presentation features and outcome of patients who have survived greater than 7.5 years.
Methods: Patients selected were those randomised to conventional (melphalan and ABCM based) therapy who survived greater than 7.5 years; all of these patients had achieved a plateau phase. Their presenting clinical and laboratory features were compared to a group of patients (matched by trial and treatment) who also reached plateau but were the first of the cohort to die directly from MM. Time to response and absolute response was calculated. Clinical course and performance status were assessed from 3 month follow-up clinical data forms and central laboratory paraprotein analysis.
Results: 239/2781 (8.5%) of eligible patients survived greater than 7.5 years. 170 patients had died (median and interquartile range (IQR) 9.5 years and 8.3–11.7 years) and 69 patients were still alive at the time of the analysis, median follow-up of 11.4 years (IQR 9.2–14.1 years). Compared to the matched short-lived control group, these long term survivors had lower β2-microglobulin, preserved albumin, lower marrow plasmacytosis, less renal impairment, better performance status, fewer fractures, less bone pain and fewer lytic lesions at presentation. There were no differences in age, lymphocytes, or depth of serological response, however, median time to reach plateau was delayed for the long term survivors {0.77 years (IQR 0.41–1.05) versus 0.42 years (0.26–0.73 for controls)}. 35 patients remain in first plateau with no progression, 28 patients died in first plateau most commonly of vascular disease (25%) or cancer (21%). 176 patients relapsed and 11 (6%) died of myeloma in first relapse, however the majority (140/176, 80%) achieved a second plateau and having relapsed a second time 53/114 (46%) achieved a third plateau. 43 of these 140 patients died in second plateau or beyond of a cause other than myeloma - (vascular 7/43 (16%), cancer 5/43 (12%), renal 5/43 (12%), infection 6/43 (14%), other 4/43 (9%). 30/239 patients (13%) died with no information on disease status or cause of death. Following second relapse 73/114 (64%) patients died directly as a result of myeloma. Time spent in performance status 1 and 2 was 96% for plateau 1, 83% for relapse 1 and 63% beyond relapse 2.
Conclusions: 8.5% of MRC trial patients receiving conventional non-intensive therapy survive greater than 7.5 years. Factors associated with long survival include low disease burden, better performance status and less end organ damage. Absolute serological response had no bearing on overall outcome; however rapid response is associated with poorer survival. The existence of second and subsequent plateau phases of MM, have rarely been documented in the literature. A large proportion of time following relapse is spent with good performance status, suggesting that patients experience a good quality of life during much of this period.