Recognition of early mortality in multiple myeloma by a prediction matrix

Abstract

Early mortality (EM; death ≤ 6 months from diagnosis) has been reported in several newly diagnosed multiple myeloma (NDMM) trials. Before the era of novel agents, the incidence was 10%‐14%. Causes of death included infections/pneumonia, renal failure, refractory disease, and cardiac events. Staging systems, such as the revised International Staging System (r‐ISS), and prognostic factors including cytogenetics, lactate dehydrogenase levels, and myeloma‐specific factors, are useful to assess overall prognosis; however, they cannot predict EM. We evaluated patients treated with novel agents in the Connect MM® Registry and identified risk factors of the EM cohort. Eligible patients were enrolled in the registry within 60 days of diagnosis. Univariate and multivariate analyses were conducted to evaluate associations between baseline characteristics and EM. Prediction matrices for EM were constructed from a logistic model. Between September 2009 and December 2011, 1493 patients were enrolled in the registry and had adequate follow‐up. Of these patients, 102 (6.8%) had EM and 1391 (93.2%) survived for > 180 days. Baseline factors significantly associated with increased EM risk included age > 75 years, higher Eastern Cooperative Oncology Group performance status, lower EQ‐5D mobility score, higher ISS stage, lower platelet count, and prior hypertension. Renal insufficiency trended toward increased EM risk. These risk factors were incorporated into a prediction matrix for EM. The EM prediction matrix uses differential weighting of risk factors to calculate EM risk in patients with NDMM. Identifying patients at risk for EM may provide new opportunities to implement patient‐specific treatment strategies to improve outcomes.

Impact of post-ASCT maintenance therapy on outcomes in patients with newly diagnosed multiple myeloma in Connect MM

“…All participants gave written informed consent upon enrollment, and study sites obtained approvals from their local or central institutional review boards or ethics committees. 9,11 For this analysis, patients from cohort 1 (N 5 1493) who received induction therapy and ASCT were included. The date of data cutoff was 7 January 2016.…”

Validation of multiple myeloma risk stratification indices in routine clinical practice: Analysis of data from the Czech Myeloma Group Registry of Monoclonal Gammopathies

“…In particular, poor performance status reported in our cohort of Stage II and Stage III R‐ISS patients could potentially worsen the outcome of these patients (10.6% and 14.3% PS 4) due to the fact that proper treatment could not be delivered. Performance status is an important independent prognostic indicator of survival24 not reflected in R‐ISS. There is also the fact that R‐ISS patient Stage II and Stage III are older than those of Stage I and poor performance status as well as more cytogenetic changes are expected in this population.…”

Development of a prognostic model for overall survival in multiple myeloma using the Connect® MM Patient Registry

“…Although novel agents, ASCT and triplet therapy have contributed to longer OS in patients with NDMM (San Miguel et al , ; Warren et al , ; Roussel et al , ; Rajkumar, ; Attal et al , ; Durie et al , ; Kastritis et al , ), these improvements are greatly affected by baseline characteristics (Biran et al , ; ). This is the first application of a novel prognostic tool to a heterogeneous [community (81%), academic (18%) and government (1%) settings] patient population from the Connect MM Registry to identify prognostic factors for long‐term survival (Rifkin et al , ) and the second application to examine outcomes and survival (Terebelo et al , ). This analysis identified patient‐, disease‐, quality‐of‐life and treatment‐specific factors known to affect OS, including age, history of diabetes, mobility, del(17p), triplet therapy use and ISS stage in data from patients more representative of typical clinical settings than randomized clinical trials (Wu et al , ; Harousseau & Attal, ; Kastritis et al , ).…”

“…Cohort 1 data were used to evaluate the association of baseline characteristics with OS; variables represented a comprehensive set of patient‐ and disease‐related characteristics and were not pre‐selected (Terebelo et al , ). A multistep analysis was conducted to compensate for missing data attributable to the noninterventional nature of registry studies (Data S1) (Srinivasan et al , ).…”

“…External validation was performed using data from Cohort 2 of the Connect MM Registry (median follow‐up = 18·3 months [range 0·2–41·9 months]) and from Celgene‐sponsored randomized phase 3 trials in patients with NDMM (MM‐015 [ N = 459] and MM‐020 [FIRST; Frontline Investigation of Lenalidomide + Dexamethasone Versus Standard Thalidomide; N = 1623]) (Palumbo et al , ; Benboubker et al , ; Terebelo et al , ; Srinivasan et al , ). Details of external validation, including the conversion and estimation of EQ‐5D mobility scores and Eastern Cooperative Oncology Group (ECOG) PS, are presented in the Data S1.…”