Systematic Evaluation of Mortality Causes in Multiple Myeloma Patients
Overview
In a cohort of 617 multiple myeloma (MM) patients who died during follow-up, 83% of deaths were MM-dependent, with half due to MM progression and 19% therapy-related. Therapy-associated deaths, especially infections including COVID-19, peaked early after therapy start and during the pandemic, impacting survival trends.
Background
Multiple myeloma is a hematological malignancy characterized by clonal plasma cell expansion with an incidence of approximately 9 per 100,000 annually in Germany. Despite advances in diagnosis and treatment, MM remains largely incurable with a five-year survival rate around 57%. Novel therapies have increased therapy-associated complications such as infections and second primary malignancies, necessitating detailed cause of death (COD) analyses to guide clinical management.
Data Highlights
COD Category
Number of Patients (n=500)
Percentage
MM-dependent (total)
413
83%
- MM-progression-related (IA)
249
50%
- Therapy-related (IB)
97
19%
- Not attributable to IA/IB (IC)
67
13%
MM-independent (II)
87
17%
Key Findings
Among known causes of death, 83% were MM-dependent, predominantly due to MM progression (50%) and therapy-related causes (19%).
Therapy-related deaths peaked early after therapy initiation (21–29%) and decreased with longer survival (8–17%).
Infections, including COVID-19, pneumonia, and sepsis, were major contributors to therapy-related deaths, especially during the 2019–2021 pandemic period.
Second primary malignancies (SPM), mainly hematological (AML, MDS), accounted for an increasing proportion of therapy-related deaths with longer survival.
Survival improved from 2014 to 2019 but declined during the COVID-19 pandemic, primarily driven by increased infection-related therapy deaths, before rising again post-2021.
Kaplan-Meier and Cox analyses demonstrated significantly decreased survival associated with therapy-related deaths during the pandemic compared to MM progression or MM-independent causes.
Clinical Implications
Clinicians should closely monitor MM patients for therapy-related complications, particularly infections, early after treatment initiation. The COVID-19 pandemic highlighted the vulnerability of MM patients to infectious causes of death, underscoring the importance of infection prevention and management strategies. Awareness of increasing second primary malignancies with prolonged survival is critical for long-term patient care.
Conclusion
This systematic evaluation reveals that MM progression and therapy-related complications, especially infections, are the leading causes of death in MM patients. Understanding temporal trends in COD can inform tailored clinical interventions to improve survival outcomes.
References
GMMG-HD6 and GMMG-HD7 Trials (NCT02495922, NCT03617731) -- Clinical Trial Data
Heidelberg-MM-registry (Ethics S-096/2017) -- Prospective MM Patient Data
by Jia xiang Jin, Britta Besemer, Büsranur Yilmaz, Mathias Hänel, Roland Fenk, Uta Bertsch, Kaarina-Jiayuan Gu, Christine Hanoun, Igor W. Blau, Christoph Mann, Christof Scheid, Roland Schroers, Ivana von Metzler, Manfred Hensel, Eva-Maria Klein, Martin Hoffmann, Christoph Lutz, Hendrik Riesenberg, Uwe M. Martens, Christian S. Michel, Christian Kunz, Evgenii Shumilov, Deniz Gezer, Tobias A. W. Holderried, Karolin Trautmann-Grill, Carsten Müller-Tidow, Katja C. Weisel, Marc S. Raab, Hans J. Salwender, Hartmut Goldschmidt, Elias K. Mai
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