Carfilzomib’s Real-World Safety Outcomes in Korea: Target Trial Emulation Study Using Electronic Health Records
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Source
2.2. Study Design
2.3. Study Population
2.4. Exposures
2.5. Outcomes
2.6. Covariates
2.7. Statistical Analysis
3. Results
3.1. Demographics
3.2. Risk of Safety Outcomes in KRd Users
3.3. Sensitivity Analyses
4. Discussion
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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KRd (n = 69) | Rd (n = 69) | p-Value | |
---|---|---|---|
Age—years ‡ | 64 (45–80) | 67 (39–85) | 0.04 * |
Male sex † | 40 (58.0) | 39 (56.5) | 0.86 |
Number of prior regimens § | 2.0 ± 1.0 | 2.0 ± 1.2 | 0.76 |
Disease stage at initial diagnosis † | |||
I | 15 (21.7) | 4 (5.8) | 0.11 |
II | 18 (26.1) | 16 (23.2) | |
III | 13 (18.8) | 13 (18.8) | |
Unknown | 23 (33.3) | 36 (52.2) | |
Creatinine clearance—mL/min § | 84.0 ± 39.4 | 60.1 ± 21.0 | 0.76 |
<50mL/min † | 14 (20.3) | 19 (27.5) | 0.32 |
≥50mL/min † | 55 (79.7) | 50 (72.5) | 0.32 |
Prior therapies † | |||
Bortezomib | 64 (92.8) | 62 (90.0) | 0.55 |
Lenalidomide | 1 (1.4) | 0 | 0.48 |
Any immunomodulatory agent | 16 (23.2) | 25 (36.2) | 0.09 |
Concurrent conditions† | |||
Major surgery | 0 (0) | 2 (2.9) | 0.24 |
Active infection requiring treatments | 2 (2.9) | 3 (4.3) | 0.55 |
Human immunodeficiency virus infection | 0 (0) | 0 (0) | - |
Active hepatitis B or C infection | 7 (10.1) | 4 (5.8) | 0.35 |
Other malignancy | 4 (5.8) | 4 (5.8) | 1.00 |
Peripheral neuropathy | 30 (43.5) | 34 (49.3) | 0.50 |
Ongoing graft-vs-host disease | 0 (0) | 1 (1.4) | 0.48 |
Pleural effusion or ascites | 0 (0) | 0 (0) | - |
Cardiac conditions † | |||
Myocardial infarction | 0 (0) | 1 (1.4) | 0.48 |
Heart failure | 2 (2.9) | 4 (5.8) | 0.40 |
Angina | 3 (4.3) | 1 (1.4) | 0.31 |
Coronary artery disease | 1 (1.4) | 3 (4.3) | 0.31 |
Ventricular arrhythmia | 0 (0) | 0 (0) | - |
Sick sinus syndrome | 1 (1.4) | 1 (1.4) | 1.00 |
Acute ischemia | 0 (0) | 0 (0) | - |
Conduction system abnormalities | 0 (0) | 0 (0) | - |
Hypertension | 18 (26.1) | 23 (33.3) | 0.35 |
Diabetes | 16 (23.2) | 16 (23.2) | 1.00 |
KRd (n = 69) | Incidence Rate in Each Cycle (%) | Rd (n = 69) | Incidence Rate in Each Cycle (%) | |
---|---|---|---|---|
Treatment cycles during specified period † | ||||
Cycles 1–6 | 69 (100.0) | - | 69 (100.0) | - |
Cycles 7–12 | 29 (42.0) | 44 (63.8) | ||
Cycles 13–18 | 7 (10.1) | 31 (44.9) | ||
Number of treatment cycles ‡ | 6 (1-18) | 12 (1-18) | ||
Adverse event by treatment cycle † | ||||
Nonhematologic adverse events | ||||
Dyspnea | ||||
Cycles 1–6 | 25 | (36.2) | 16 | (23.2) |
Cycles 7–12 | 4 | (13.8) | 2 | (4.5) |
Cycles 13–18 | 1 | (14.3) | 1 | (3.2) |
Hypertension | ||||
Cycles 1–6 | 17 | (24.6) | 19 | (27.5) |
Cycles 7–12 | 5 | (17.2) | 2 | (4.5) |
Cycles 13–18 | 1 | (14.3) | 5 | (16.1) |
Acute renal failure | ||||
Cycles 1–6 | 9 | (13.0) | 9 | (13.0) |
Cycles 7–12 | 2 | (6.9) | 1 | (2.3) |
Cycles 13–18 | 0 | 0 | 0 | 0 |
Cardiac failure | ||||
Cycles 1–6 | 9 | (13.0) | 9 | (13.0) |
Cycles 7–12 | 1 | (3.4) | 2 | (4.5) |
Cycles 13–18 | 1 | (14.3) | 0 | 0 |
Ischemic heart disease | ||||
Cycles 1–6 | 5 | (7.2) | 7 | (10.1) |
Cycles 7–12 | 1 | (3.4) | 1 | (2.3) |
Cycles 13–18 | 0 | 0 | 1 | (3.2) |
Diarrhea | ||||
Cycles 1–6 | 11 | (15.9) | 17 | (24.6) |
Cycles 7–12 | 5 | (17.2) | 2 | (4.5) |
Cycles 13–18 | 1 | (14.3) | 0 | 0 |
Cough | ||||
Cycles 1–6 | 9 | (13.0) | 11 | (15.9) |
Cycles 7–12 | 2 | (6.9) | 2 | (4.5) |
Cycles 13–18 | 0 | (0.0) | 0 | 0 |
Pyrexia | ||||
Cycles 1–6 | 23 | (33.3) | 15 | (21.7) |
Cycles 7–12 | 3 | (10.3) | 5 | (11.4) |
Cycles 13–18 | 2 | (28.6) | 1 | (3.2) |
Upper respiratory tract infection | ||||
Cycles 1–6 | 9 | (13.0) | 5 | (7.2) |
Cycles 7–12 | 2 | (6.9) | 4 | (9.1) |
Cycles 13–18 | 0 | 0 | 1 | (3.2) |
Hypokalemia | ||||
Cycles 1–6 | 6 | (8.7) | 3 | (4.3) |
Cycles 7–12 | 3 | (10.3) | 2 | (4.5) |
Cycles 13–18 | 0 | 0 | 0 | 0 |
Muscle spasm | ||||
Cycles 1–6 | 8 | (11.6) | 2 | (2.9) |
Cycles 7–12 | 1 | (3.4) | 0 | 0 |
Cycles 13–18 | 0 | 0 | 0 | 0 |
Hematologic adverse events | ||||
Thrombocytopenia | ||||
Cycles 1–6 | 29 | (42.0) | 24 | (34.8) |
Cycles 7–12 | 8 | (27.6) | 3 | (6.8) |
Cycles 13–18 | 1 | (14.3) | 1 | (3.2) |
KRd (n = 69) | Rd (n = 69) | Adjusted HR ¥ (95% CI) | |||
---|---|---|---|---|---|
Events | Events/100-Patient Cycle | Events | Events/100-Patient Cycle | ||
Nonhematologic adverse reactions | |||||
Dyspnea | 30 | 9.84 | 19 | 3.11 | 2.27 (1.24–4.16) |
Hypertension | 23 | 6.04 | 26 | 4.44 | 1.32 (0.73–2.41) |
Acute renal failure | 11 | 2.66 | 10 | 1.41 | 1.3 (0.53–3.16) |
Cardiac failure | 11 | 2.66 | 11 | 1.63 | 1.45 (0.61–3.48) |
Ischemic heart disease | 6 | 1.38 | 9 | 1.36 | 1 (0.34–2.92) |
Diarrhea ¶ | 17 | 4.51 | 19 | 3.13 | 1.02 (0.52–2.01) |
Cough ¶ | 11 | 2.95 | 13 | 1.99 | 1.06 (0.45–2.46) |
Pyrexia ¶ | 28 | 8.14 | 21 | 3.33 | 1.79 (0.99–3.26) |
Upper respiratory tract infection ¶ | 11 | 2.96 | 10 | 1.53 | 1.45 (0.59–3.57) |
Hypokalemia ¶ | 9 | 2.05 | 5 | 0.7 | 1.91 (0.62–5.88) |
Muscle spasm ¶ | 9 | 2.24 | 2 | 0.27 | 5.12 (1.05–24.94) |
Hematologic adverse reactions | |||||
Thrombocytopenia ¶ | 38 | 12.71 | 28 | 5.12 | 1.84 (1.1–3.06) |
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Jang, H.Y.; Lee, H.K.; Kim, C.J.; Yoon, S.-S.; Kim, I.-W.; Oh, J.M. Carfilzomib’s Real-World Safety Outcomes in Korea: Target Trial Emulation Study Using Electronic Health Records. Int. J. Environ. Res. Public Health 2022, 19, 13560. https://doi.org/10.3390/ijerph192013560
Jang HY, Lee HK, Kim CJ, Yoon S-S, Kim I-W, Oh JM. Carfilzomib’s Real-World Safety Outcomes in Korea: Target Trial Emulation Study Using Electronic Health Records. International Journal of Environmental Research and Public Health. 2022; 19(20):13560. https://doi.org/10.3390/ijerph192013560
Chicago/Turabian StyleJang, Ha Young, Hyun Kyung Lee, Chae Jeong Kim, Sung-Soo Yoon, In-Wha Kim, and Jung Mi Oh. 2022. "Carfilzomib’s Real-World Safety Outcomes in Korea: Target Trial Emulation Study Using Electronic Health Records" International Journal of Environmental Research and Public Health 19, no. 20: 13560. https://doi.org/10.3390/ijerph192013560