Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Patients
2.2. Treatment, Response, and Outcome
2.3. Adverse Events and Hematological Recovery
2.4. Measurable Residual Disease (MRD)
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Risk Classification
4.3. Study Design and Chemotherapy
4.4. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Standard Arm (n = 115) | Tosedostat 120 mg (n = 116) | Total | |
---|---|---|---|
Sex | |||
M | 72 (63%) | 76 (66%) | 148 (64%) |
F | 43 (37%) | 40 (34%) | 83 (36%) |
Age groups | |||
≤70 years | 72 (63%) | 64 (55%) | 136 (59%) |
>70 years | 43 (37%) | 52 (45%) | 95 (41%) |
Age | |||
Mean; SD | 69.9; 3.26 | 70.7; 3.75 | 70.3; 3.53 |
Median; range | 69; 66–79 | 70; 66–81 | 70; 66–81 |
WHO performance | |||
0 | 63 (55%) | 54 (47%) | 117 (51%) |
1 | 43 (37%) | 50 (43%) | 93 (40%) |
2 | 8 (7%) | 11 (9%) | 19 (8%) |
NA | 1 (1%) | 1 (1%) | 2 (1%) |
Diagnosis | |||
MDS | 15 (13%) | 16 (14%) | 31 (13%) |
AML | 100 (87%) | 100 (86%) | 200 (87%) |
Prior HM | |||
No | 109 (95%) | 106 (93%) | 215 (94%) |
Yes | 6 (5%) | 8 (7%) | 14 (6%) |
AML risk group (acc. to HOVON 103 protocol) * | |||
Good | 8 (7%) | 2 (2%) | 10 (4%) |
Intermediate | 35 (30%) | 39 (34%) | 74 (32%) |
Poor | 60 (52%) | 57 (49%) | 117 (51%) |
Very poor | 12 (10%) | 18 (16%) | 30 (13%) |
NPM1 mutation | |||
Neg | 51 (44%) | 53 (46%) | 104 (45%) |
Pos | 19 (17%) | 19 (16%) | 38 (16%) |
NA | 45 (39%) | 44 (38%) | 89 (39%) |
FLT3ITD | |||
Neg | 60 (52%) | 67 (58%) | 127 (55%) |
Pos | 12 (10%) | 7 (6%) | 19 (8%) |
NA | 43 (37%) | 42 (36%) | 85 (37%) |
FLT3 TKD835 | |||
Neg | 33 (29%) | 31 (27%) | 64 (28%) |
Pos | 2 (2%) | 3 (3%) | 5 (2%) |
NA | 80 (70%) | 82 (71%) | 162 (70%) |
EVI1 overexpression | |||
Neg | 65 (57%) | 61 (53%) | 126 (55%) |
Pos | 8 (7%) | 11 (9%) | 19 (8%) |
NA | 42 (37%) | 44 (38%) | 86 (37%) |
CEBPA DM | |||
Neg | 63 (55%) | 68 (59%) | 131 (57%) |
Pos | 4 (3%) | 2 (2%) | 6 (3%) |
NA | 48 (42%) | 46 (40%) | 94 (41%) |
FLT3ITD × NPM1 mutation | |||
Pos × Pos | 9 (8%) | 5 (4%) | 14 (6%) |
Pos × neg | 3 (3%) | 1 (1%) | 4 (2%) |
Neg × Pos | 10 (9%) | 14 (12%) | 24 (10%) |
Neg × Neg | 47 (41%) | 50 (43%) | 97 (42%) |
NA | 46 (40%) | 46 (40%) | 92 (40%) |
Standard Treatment | Tosedostat 120 mg | HR (95%-C.I.) | p | |
---|---|---|---|---|
Complete remission (CR/CRi) (95% C.I.) | 69% (60–77) | 64% (55–73) | 0.431 | |
CR/CRi (after cycle I) | 54% | 56% | ||
PR (after cycle 1) | 4% | 5% | ||
RD (after cycle 1) | 24% | 18% | ||
PR (after cycle 2) | 0% | 0% | ||
RD (after cycle 2) | 6% | 6% | ||
Death within 30 days | 8% | 19% | ||
Death within 60 days | 19% | 28% | ||
OS at 2 years | 33 | 18 | 1.51 (1.12–2.03) | 0.006 |
EFS at 2 years | 20 | 12 | 1.44 (1.08–1.90) | 0.01 |
DFS at 2 years | 28 | 17 | 1.51 (1.06–2.16) | 0.02 |
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Janssen, J.; Löwenberg, B.; Manz, M.; Bargetzi, M.; Biemond, B.; Borne, P.v.d.; Breems, D.; Brouwer, R.; Chalandon, Y.; Deeren, D.; et al. Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS. Cancers 2021, 13, 672. https://doi.org/10.3390/cancers13040672
Janssen J, Löwenberg B, Manz M, Bargetzi M, Biemond B, Borne Pvd, Breems D, Brouwer R, Chalandon Y, Deeren D, et al. Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS. Cancers. 2021; 13(4):672. https://doi.org/10.3390/cancers13040672
Chicago/Turabian StyleJanssen, Jeroen, Bob Löwenberg, Markus Manz, Mario Bargetzi, Bart Biemond, Peter von dem Borne, Dimitri Breems, Rolf Brouwer, Yves Chalandon, Dries Deeren, and et al. 2021. "Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS" Cancers 13, no. 4: 672. https://doi.org/10.3390/cancers13040672