A systematic classification of death causes in multiple myeloma

Elias, K.; Haas, Eva; Lücke, Stephan; Löpprich, Martin; Kunz, Christina; Pritsch, Maria; Knaup, Petra; Raab, Marc-Steffen; Schlenzka, Jana; Bertsch, Uta; Hillengaß, Jens; Goldschmidt, Hartmut

doi:10.1038/s41408-018-0068-5

Cited by 31 publications

(24 citation statements)

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“…11,12 Death during active treatment is not only an issue at 1L; a substantial proportion of patients at each line died while on active treatment (more than one-third of patients overall fections and 13% to renal disorders. 15 A study using the Connect ® MM Registry identified predictors of early death (defined as death within the first 6 months after diagnosis). 9 These predictors included age over 75 years, worse performance status, adverse cytogenetics, lower mobility score, higher ISS stage, lower platelet count and previous history of hypertension.…”

Section: Discussionmentioning

confidence: 99%

Understanding mortality in multiple myeloma: Findings of a European retrospective chart review

Mohty

Cavo²,

Fink³

et al. 2019

European J of Haematology

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ObjectivesThis study aimed to provide real‐world data on the characteristics and treatment of patients with multiple myeloma (MM) at the time of death.MethodsThe study was a retrospective patient chart review across France, Germany, Italy, Spain and the UK during 2016, and included patients who had died in the 3 months before the index date.ResultsData from 786 patients were reviewed. At the time of death, 37% of patients were receiving active treatment, 12% were in a treatment‐free interval and 51% were receiving only supportive care. Death before and during active first‐line treatment was not uncommon (6% and 24% of patients, respectively) but these deaths were often not solely due to disease progression; factors such as renal failure and infection frequently played a role (in 30% and 20% of patients at first‐line, respectively). Most deaths at later lines were due to progressive disease. Cox model results suggested that early deaths were associated with advanced disease stage, high‐risk cytogenetics and poor response and relapse profiles.ConclusionsThese real‐world data could be used to help develop strategies for improving survival in patients with MM and to support management tailored to the stage of disease.

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Section: Discussionmentioning

confidence: 99%

Understanding mortality in multiple myeloma: Findings of a European retrospective chart review

Mohty

Cavo²,

Fink³

et al. 2019

European J of Haematology

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“…Risk of VTE is even greater in MM patients treated with immunomodulatory (IMID) drugs (eg, lenalidomide), or additional thrombogenic drugs (eg, dexamethasone) . With treatment advances transforming MM from a fatal disease to a chronic one, a common cause of death in this population is VTE . Despite the overall reduction in MM‐related mortality, MM patients with VTE have a 3‐fold increased risk of death at one year following MM diagnosis compared to MM patients without VTE …”

Section: Introductionmentioning

confidence: 99%

Predicting venous thromboembolism in multiple myeloma: development and validation of the IMPEDE VTE score

et al. 2019

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Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). The International Myeloma Working Group (IMWG) developed guidelines recommending primary thromboprophylaxis, in those identified at high‐risk of VTE by the presence of risk factors. The National Comprehensive Cancer Network (NCCN) has adopted these guidelines; however, they lack validation. We sought to develop and validate a risk prediction score for VTE in MM and to evaluate the performance of the current IMWG/NCCN guidelines. Using 4446 patients within the Veterans Administration Central Cancer Registry, we used time‐to‐event analyses to develop a risk score for VTE in patients with newly diagnosed MM starting chemotherapy. We externally validated the score using the Surveillance, Epidemiology, End Results (SEER)‐Medicare database (N = 4256). After identifying independent predictors of VTE, we combined the variables to develop the IMPEDE VTE score (Immunomodulatory agent; Body Mass Index ≥25 kg/m2; Pelvic, hip or femur fracture; Erythropoietin stimulating agent; Dexamethasone/Doxorubicin; Asian Ethnicity/Race; VTE history; Tunneled line/central venous catheter; Existing thromboprophylaxis). The score showed satisfactory discrimination in the derivation cohort, c‐statistic = 0.66. Risk of VTE significantly increased as score increased (hazard ratio 1.20, P = <.0001). Within the external validation cohort, IMPEDE VTE had a c‐statistic of 0.64. For comparison, when evaluating the performance of the IMWG/NCCN guidelines, the c‐statistic was 0.55. In summary, the IMPEDE VTE score outperformed the current IMWG/NCCN guidelines and could be considered as the new standard risk stratification for VTE in MM.

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“…Despite advances in the treatment and management of multiple myeloma (MM) over the past 15 years, relapsed and/or refractory MM remains a common and life‐threatening diagnosis . Optimal therapy given at first relapse of MM is important for achieving maximal treatment response and prolonged survival .…”

Section: Introductionmentioning

confidence: 99%

Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study

et al. 2019

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Twice‐weekly carfilzomib (27 mg/m2) with lenalidomide‐dexamethasone (KRd) is a standard‐of‐care in relapsed or refractory multiple myeloma (RRMM). This phase 1b study evaluated KRd with once‐weekly carfilzomib in RRMM. Patients received carfilzomib (30‐minute infusion; 56 or 70mg/m2) on days 1, 8, and 15; lenalidomide 25 mg on days 1‐21; and dexamethasone 40 mg on days 1, 8, 15, and 22 (day 22 omitted for cycles 9+) of 28‐day cycles. Primary objective was safety/tolerability; efficacy was a secondary objective. Fifty‐six RRMM patients enrolled: 22 during dose evaluation (56‐mg/m2, n = 10; 70‐mg/m2, n = 12) and 34 during dose expansion (all initiated dosing at 70 mg/m2). After 2 fatal adverse events (AEs) during 70‐mg/m2 dose expansion, dosage reduction to 56 mg/m2 was permitted. Results are presented for carfilzomib 56‐mg/m2 (n = 10) and 70‐mg/m2 groups (dose evaluation/expansion; n = 46). Median carfilzomib dose was 53.2 mg/m2 (56‐mg/m2 group) and 62.4 mg/m2 (70‐mg/m2 group). Grade ≥3 AE rates were 70.0% (56 mg/m2) and 69.6% (70 mg/m2). Overall response rates were 90.0% (56 mg/m2) and 89.1% (70 mg/m2); ≥very good partial response rates were 50.0% (56 mg/m2) and 73.9% (70 mg/m2). Once‐weekly KRd was active with acceptable toxicity in RRMM, supporting further evaluation of this regimen.

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A systematic classification of death causes in multiple myeloma

Cited by 31 publications

References 10 publications

Understanding mortality in multiple myeloma: Findings of a European retrospective chart review

Understanding mortality in multiple myeloma: Findings of a European retrospective chart review

Predicting venous thromboembolism in multiple myeloma: development and validation of the IMPEDE VTE score

Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study

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