Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design, Ethics and Patients
2.2. Outcomes Measures
2.3. Development of Serum Bortezomib Concentration Measurement Method
2.4. Statistical Analysis
3. Results
3.1. Development of Serum Bortezomib Concentration Measurement Method
3.2. Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea
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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Character | Patients without Diarrhea | Patients with Diarrhea | p Value | |||
---|---|---|---|---|---|---|
Baseline characteristics | ||||||
Male/female (male %) | 11/5 (68.8%) | 4/4 (50%) | 0.412 | |||
Age, years | 77 | (49–83) | 62 | (54–71) | 0.008 * | |
Height, cm | 160.9 | (145.1–171.2) | 162.1 | (140.0–167.4) | 0.811 | |
Weight, kg | 57.4 | (43–78.4) | 60.4 | (38.6–71.2) | 0.893 | |
Serum albumin, g/dL | 3.3 | (1.3–5.9) | 3.8 | (2.5–4.6) | 0.579 | |
Blood urea nitrogen, mg/dL | 19.3 | (11.4–70.4) | 12.8 | (6.8–23.1) | 0.033 | |
Serum creatinine, mg/dL | 0.97 | (0.42–8.01) | 0.74 | (0.47–1.33) | 0.229 | |
Total bilirubin, mg/dL | 0.55 | (0.30–1.00) | 0.65 | (0.40–2.30) | 0.195 | |
Alanine transaminase, IU/L | 19 | (11–68) | 22.5 | (14–66) | 0.475 | |
Aspartate transaminase, IU/L | 22 | (9–90) | 17 | (10–54) | 0.696 | |
γ-glutamyl transpeptidase, IU/L | 24 | (7–125) | 29 | (11–343) | 0.427 | |
Cholinesterase, IU/L | 237 | (102–451) | 244 | (113–321) | 0.634 | |
White blood cell, counts × 103/μL | 5 | (2.9–8.7) | 3.5 | (1.6–10.1) | 0.387 | |
Red blood cell, counts × 106/μL | 3.7 | (2.7–5.0) | 3.5 | (2.8–4.9) | 0.773 | |
Hemoglobin, g/dL | 11.8 | (8.6–15.4) | 9.9 | (0.8–15.7) | 0.377 | |
Hematocrit, % | 36.1 | (27.4–43.7) | 33.7 | (22.9–47.7) | 0.993 | |
Platelet, counts × 103/μL | 190 | (56–315) | 159 | (53–246) | 0.424 | |
Prothrombin time, % | 94 | (11–134) | 90 | (61–137) | 0.605 | |
Prothrombin time-international normalized ratio | 1.02 | (0.89–1.76) | 1.05 | (0.89–1.26) | 0.610 | |
Comorbidities | ||||||
Hypertension (%) | 7 (43.8%) | 3 (37.5%) | 1.000 | |||
Chronic kidney disease (%) | 6 (37.5%) | 0 (0.0%) | 0.066 | |||
Diabetes mellitus (%) | 2 (12.5%) | 2 (25.0%) | 0.578 | |||
Solid carcinoma (%) | 3 (18.8%) | 1 (12.5%) | 1.000 | |||
Heart failure (%) | 7 (43.8%) | 2 (25.0%) | 0.657 | |||
Liver disiease (%) | 7 (43.8%) | 2 (25.0%) | 0.657 | |||
Alcohol consumption | 5 (31.3%) | 3 (37.5%) | 1.000 | |||
Multiple myeloma type | 0.674 | |||||
IgGκ (%) | 6 (37.5%) | 4 (25.0%) | ||||
IgGλ (%) | 0 (0.0%) | 1 (6.3%) | ||||
IgAκ (%) | 1 (6.3%) | 1 (6.3%) | ||||
IgAλ (%) | 2 (12.5%) | 0 (0%) | ||||
AL amyloidosis (%) | 4 (25.0%) | 1 (6.3%) | ||||
Ohters (%) | 3 (18.8%) | 1 (6.3%) | ||||
Recurrence (%) | 4 (25.0%) | 4 (50.0%) | 0.363 | |||
Gastrointestinal amyloidosis | 3 (18.8%) | 0 (0%) | 0.526 | |||
Disease stage | ||||||
I | 7 (43.8%) | 7 (87.5%) | 0.079 | |||
II | 5 (31.3%) | 1 (12.5%) | 0.621 | |||
III | 4 (25.0%) | 0 (0.0%) | 0.262 | |||
Exposure | ||||||
Measured concentration, ng/mL | 0.48 | (0.26–0.67) | 0.87 | (0.66–2.23) | 0.040 * | |
Measurement after second dose | 4 (25.0%) | 3 (37.5%) | 0.866 | |||
Dose, mg/m2 | 0.657 | |||||
1.3 mg/m2 (%) | 9 (56.2%) | 6 (75.0%) | ||||
1.0 mg/m2 (%) | 7 (43.8%) | 2 (25.0%) | ||||
Body surface area, m2 | 1.6 | (1.3–1.9) | 1.6 | (1.3–1.8) | 1.000 | |
Dose, mg | 1.7 | (1.5–2.4) | 1.9 | (1.6–2.2) | 0.433 | |
Concentration/dose, (ng/mL)/(mg/m2) | 0.5 | (0.0–1.0) | 0.8 | (0.3–1.9) | 0.020 | |
Injection route | ||||||
Subcutaneous injection (%) | 15 (93.8%) | 8 (100%) | 1.000 | |||
Intravenous injection (%) | 1 (6.3%) | 0 (0.0%) | 1.000 | |||
Concomitant CYP 2C19 inhibitors | ||||||
Lansoprazole (%) | 7 (43.8%) | 2 (25.0%) | 0.657 | |||
Esomeprazole (%) | 5 (31.3%) | 2 (25.0%) | 1.000 | |||
Rabeprazole (%) | 1 (6.3%) | 3 (37.5%) | 0.091 | |||
Vonoprazan (%) | 1 (6.3%) | 0 (0.0%) | 1.000 | |||
Fluconazole (%) | 1 (6.3%) | 0 (0.0%) | 1.000 | |||
Concomitant CYP 3A4 inhibitors | ||||||
Dexamethasone (%) | 15 (93.8%) | 7 (87.5%) | 1.000 | |||
Concomitant CYP 3A4 inducers | ||||||
Amlodipine (%) | 1 (6.3%) | 3 (37.5%) | 0.091 | |||
Fluconazole (%) | 1 (6.3%) | 0 (0.0%) | 1.000 | |||
Others (%) | 3 (18.8%) | 1 (12.5%) | 1.000 | |||
Regimens | ||||||
Bor + CPA + DEX (%) | 12 (75.0%) | 5 (62.5%) | 0.647 | |||
Bor + DEX (%) | 2 (12.5%) | 1 (12.5%) | 0.333 | |||
Others (%) | 2 (12.5%) | 2 (25.0%) | 0.578 | |||
Outcomes | ||||||
Peripheral neuropathy (%) | 4 (25.0%) | 3 (37.5%) | 0.647 | |||
Fatigue (%) | 1 (6.3%) | 1 (12.5%) | 1.000 | |||
Nausea or vomiting (%) | 1 (6.3%) | 0 (0.0%) | 1.000 | |||
Constipation (%) | 9 (56.3%) | 1 (12.5%) | 0.079 | |||
Thrombocytopenia (<75,000 counts/μL%) | 8 (50%) | 5 (62.5%) | 0.679 | |||
Fever (>38 °C) (%) | 1 (6.3%) | 1 (12.5%) | 1.000 | |||
Anemia (Hb <10.0 g/dL) (%) | 12 (75%) | 6 (75%) | 1.000 | |||
Leukopenia (<3,000 counts/μL)% | 8 (50%) | 3 (37.5%) | 0.680 | |||
Response rate (%) | 12 (75.0%) | 4 (50.0%) | 0.363 |
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Fujimoto, Y.; Ueno, S.; Oda, K.; Gunda, N.; Shimomura, Y.; Nishimura, Y.; Yamaguchi, A.; Kuwano, A.; Ito, Y.; Baba, Y.; et al. Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis. Cancers 2021, 13, 5674. https://doi.org/10.3390/cancers13225674
Fujimoto Y, Ueno S, Oda K, Gunda N, Shimomura Y, Nishimura Y, Yamaguchi A, Kuwano A, Ito Y, Baba Y, et al. Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis. Cancers. 2021; 13(22):5674. https://doi.org/10.3390/cancers13225674
Chicago/Turabian StyleFujimoto, Yuki, Shikiko Ueno, Kazutaka Oda, Nao Gunda, Yumi Shimomura, Yuka Nishimura, Ayami Yamaguchi, Akari Kuwano, Yuki Ito, Yusuke Baba, and et al. 2021. "Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis" Cancers 13, no. 22: 5674. https://doi.org/10.3390/cancers13225674