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@ARTICLE{Mai:285996,
author = {E. K. Mai and T. Hielscher$^*$ and U. Bertsch and H. J.
Salwender and S. Zweegman and M. S. Raab and M. Munder and
L. Pantani and K. Mancuso and P. Brossart and M. Beksac and
I. W. Blau and J. Dürig and B. Besemer and R. Fenk and P.
Reimer and B. van der Holt and M. Hänel and I. von Metzler
and U. Graeven and C. Müller-Tidow and M. Boccadoro and C.
Scheid and M. A. Dimopoulos and J. Hillengass and K. C.
Weisel and M. Cavo and P. Sonneveld and H. Goldschmidt},
title = {{P}redictors of early morbidity and mortality in newly
diagnosed multiple myeloma: data from five randomized,
controlled, phase {III} trials in 3700 patients.},
journal = {Leukemia},
volume = {38},
number = {3},
issn = {0887-6924},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2023-02577},
pages = {640-647},
year = {2024},
note = {2024 Mar;38(3):640-647},
abstract = {Early morbidity and mortality affect patient outcomes in
multiple myeloma. Thus, we dissected the incidence and
causes of morbidity/mortality during induction therapy (IT)
for newly diagnosed multiple myeloma (NDMM), and
developed/validated a predictive risk score. We evaluated
3700 transplant-eligible NDMM patients treated in 2005-2020
with novel agent-based triplet/quadruplet IT. Primary
endpoints were severe infections, death, or a combination of
both. Patients were divided in a training (n = 1333) and
three validation cohorts (n = 2367). During IT, $11.8\%,$
$1.8\%,$ and $12.5\%$ of patients in the training cohort
experienced severe infections, death, or both, respectively.
Four major, baseline risk factors for severe infection/death
were identified: low platelet count (<150/nL), ISS III,
higher WHO performance status (>1), and age (>60 years). A
risk score (1 risk factor=1 point) stratified patients in
low $(39.5\%;$ 0 points), intermediate $(41.9\%;$ 1 point),
and high $(18.6\%;$ ≥2 points) risk. The risk for severe
infection/death increased from $7.7\%$ vs. $11.5\%$ vs.
$23.3\%$ in the low- vs. intermediate- vs. high-risk groups
(p < 0.001). The risk score was independently validated in
three trials incorporating quadruplet IT with an anti-CD38
antibody. Our analyses established a robust and easy-to-use
score to identify NDMM patients at risk of severe
infection/death, covering the latest quadruplet induction
therapies. Trial registrations: HOVON-65/GMMG-HD4: EudraCT
No. 2004-000944-26. GMMG-MM5: EudraCT No. 2010-019173-16.
GMMG-HD6: NCT02495922. EMN02/HOVON-95: NCT01208766.
GMMG-HD7: NCT03617731.},
cin = {C060},
ddc = {610},
cid = {I:(DE-He78)C060-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38062124},
doi = {10.1038/s41375-023-02105-6},
url = {https://inrepo02.dkfz.de/record/285996},
}