-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
- Cosmetic Ingredient
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Over the past 20 years, the prognosis of patients with MM has improved
with the use of novel therapies (i.
e.
, proteasome inhibitors and immunomodulatory drugs) and autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM).
Early mortality in patients with newly diagnosed MM (NDMM) within the first 6 months has been reported to be 10% to 25%
prior to the introduction of novel therapies.
The most common previously reported cause of death was infection, which may change with changes in treatment
.
Recent studies have shown that early mortality in MM patients has decreased
in the era of novel therapies.
However, these studies had limitations
due to factors such as single-centre design, selection bias (e.
g.
, use of clinical trial data), or small sample sizes.
Therefore, the investigators conducted a prospective cohort study to explore the frequency and causes of early NDMM death under the current standard of care, and to explore the predictors
of early death using clinical registry data from all NDMM patients, including the Myeloma and Related Diseases Registry (MRDR) in Australia and New Zealand.
01Research methods
The study included all patients with NDMM ≥aged 18 years aged 18 years enrolled in 36 MRDR facilities from July 2011 to March 2020, and all patients were followed for
at least 12 months.
Patient choice is given whether to consent to participate in the study in order to maximize the inclusion of all MM patients at the site and to reduce the risk of
selection bias in clinical registry studies.
The study defined early death as death
that occurred within 12 months of MM diagnosis.
Major causes of death include disease-related (directly related to MM progression or complications), infection, other non-disease causes, and unknown causes (not documented in MRDR or national death registries).
The secondary cause of death is recorded
by the National Death Registry.
The investigators used logistic regression to model the characteristics of patients and diseases at baseline and early mortality, including CCA datasets (excluding patients with missing data for one or more variables) and multiple imputation (MI) datasets
.
Variables included age, sex, disease stage (International Staging System [ISS]), karyotyping and fluorescence in situ hybridization results, Eastern Tumor Collaboration Group (ECOG) performance status, estimated glomerular filtration rate (eGFR), creatinine, platelet count, lactate dehydrogenase (LDH), albumin, serum beta-2-microglobulin, and comorbidities
.
02Study results
patient characteristics
A total of 2377 patients with NDMM (Figure 1) were included with a median age of 67.
4 (58.
9-74.
6) years at diagnosis, of which 60% were male, 31% had stage ISS-III, and 60% had ≥1 comorbidities
at diagnosis.
Figure 1
Initial treatment
94% of patients with NDMM received initial treatment
.
Bortezomib-based regimens were the most common (84%), followed by lenalidomide-containing regimens
.
Among them, bortezomib and cyclophosphamide combined with dexamethasone (VCD) regimen accounted for 71%, lenalidomide combined with dexamethasone (Rd) regimen accounted for 6%, and bortezomib combined with dexamethasone (VD) regimen accounted for 3%.
Of all patients, 1097 (51%) received ASCT
within 12 months of diagnosis.
Among patients aged ≤ 70 years, 1029 (77%) received ASCT
within 12 months of diagnosis.
Early mortality
Overall, 216 (9.
1%) patients died within 12 months of diagnosis and 119 (4.
5%) within
6 months of diagnosis.
The 1-year and 6-month mortality rates (95% CI) predicted by Kaplan–Meier were 8.
2% (7.
2%–9.
3%) and 4.
3% (3.
6%–5.
2%)
, respectively.
The patient's survival curve is shown in Figure 2
.
Figure 2
A cause of death was reported in 193 (89%) patients, and 69 (32%) patients died
from secondary causes.
Of the patients who died from major causes, 151 (78%) were disease-related, 13 (7%) were infections, and 29 (15%) were due to other causes (heart disease, renal failure, liver failure, other cancers, and trauma).
Of the patients who died from secondary causes, 38% (26/69) had infections
.
The characteristics of patients who died and survived 12 months after diagnosis are shown in Table 1
.
Table 1
Predictors of early death
In the total cohort, 1178 (50%) patients with data for all variables were included in the CCA dataset
.
After analysis using the CCA dataset, variables that remain independent predictors of early death include an age odds ratio (OR) of 1.
04, an OR of ECOG performance status of 1.
85, an OR of heart disease of 3.
00, an ISS OR of 1.
56, and an albumin OR of 0.
93
.
Although albumin levels were used to assess ISS, they were independent predictors of mortality along with ISS, suggesting that elevated albumin was associated with
reduced mortality, even when stratified by ISS stage.
The receiver operating characteristic curve (ROC) of the CCA model has an area under the curve (AUC) of 0.
83
.
To address the limitations of missing data, the researchers performed an MI dataset analysis with results similar to those of the CCA model, which had an ROC AUC of 0.
80
.
The results of multiple logistic regression analysis of CCA and MI are shown in
Table 2.
The researchers then repeated the analysis of early mortality
within 6 months.
The rest of the results were similar
except for heart disease and ISS that were not clearly associated with mortality within six months.
Table 2
03Research conclusion
The findings of the study showed that early mortality within 12 months of diagnosis in patients with NDMM was 9.
1% (4.
5% within 6 months), and disease progression was the most common cause of death, accounting for 78%
of known deaths.
Infection
is the cause of death in 7% of patients.
In 38% of patients who died from secondary causes, infection was also a major cause of
death.
Independent predictors of early death were age, comorbidities (particularly heart and lung disease), ECOG performance status, and disease severity
.
These results suggest that future research is still needed to optimize treatment
in older and/or frail NDMM patients.
References:
McQuilten Z, Wellard C, Moore E, et al.
Predictors of early mortality in multiple myeloma: Results from the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR).
Br J Haematol.
2022 Sep; 198(5):830-837.
doi: 10.
1111/bjh.
18324.
Disclaimer: This platform aims to deliver more medical information
to healthcare professionals.
The content published on this platform cannot replace professional medical guidance in any way, nor should it be regarded as diagnosis and treatment advice
.
If such information is used for purposes other than understanding medical information, this platform does not assume relevant responsibilities
.
The content published by this platform does not mean that it agrees with its description and views
.
If copyright issues are involved, please contact us and we will deal with it
as soon as possible.
Poke "Read Original" to see more
