Pharmacologic management of CAD
| . | Dose . | Overall response rate . | Definition of response . | Median duration of response . | Clinical considerations . |
|---|---|---|---|---|---|
| Rituximab | 375 mg/m2 weekly × 4 | 45%-60% | CR: normalized hemoglobin level and absence of hemolysis or CAD symptoms; PR: hemoglobin increase ≥1-2 g/dL (varies by study), transfusion independence and improved CAD symptoms, 50% reduction in IgM concentration | 6.5-11 months (observed) | Risk of rituximab infusion reactions |
| Confirm vaccination status prior to dosing | |||||
| Months for effect | |||||
| Rituximab-fludarabine | Rituximab 375 mg/m2 on days 1, 29, 57, and 85 | 76% | CR: normalized hemoglobin level, absence of hemolysis, CAD symptoms, undetectable IgM, no evidence of clonal proliferation; PR: hemoglobin increase >/ = 2 g/dL, transfusion independence and improved CAD symptoms, 50% reduction in IgM concentration | >66 months (observed) | Risk of rituximab infusion reactions |
| Not appropriate for frail patients with comorbidities due to risk for infection, neutropenia | |||||
| Fludarabine 40 mg/m2 on days 1-5, 29-34, 57-61, and 85-89 | Months for effect | ||||
| Rituximab-bendamustine | Rituximab 375 mg/m2 q28 days × 4 | 71% | CR: normalized hemoglobin level, absence of hemolysis, CAD symptoms, undetectable IgM, no evidence of clonal proliferation; PR: hemoglobin increase >/ = 2 g/dL, transfusion independence and improved CAD symptoms, 50% reduction in IgM concentration | >32 months (observed) | Risk of rituximab infusion reactions |
| Not appropriate for frail patients with comorbidities due to risk for infection, neutropenia | |||||
| Bendamustine 90 mg/m2 on days 1, 2 q28 days × 4 | Months for effect | ||||
| Eculizumab | 600 mg weekly × 4, then 900 mg every other week through week 26 | 54% | Decrease in LDH level pre and post therapy >/ = 250 U/L | Must be used continuously to maintain effect | Rapid onset; may be used as a temporizing measure |
| Vaccinate against encapsulated bacteria; meningococcal prophylaxis until vaccinated | |||||
| Will not improve acrocyanosis | |||||
| Sutimlimab | 6500 mg weekly × 2, then every other week though 26 weeks | 54% | Hemoglobin increase >/ = 1.5 g/dL, transfusion independence, no use of CAD treatments | Must be used continuously to maintain effect | Rapid onset; may be used as a temporizing measure |
| Vaccinate against encapsulated bacteria; meningococcal prophylaxis until vaccinated | |||||
| Will not improve acrocyanosis | |||||
| Ibrutinib | 420 mg/d | 100% | CR: hemoglobin >12 g/dL; PR 10-12 g/dL or ≥2 g/dL | Studies reported on ~ median of 12 months daily use | Requires acyclovir prophylaxis |
| Useful for acrocyanosis | |||||
| Bortezomib | 1.3 mg/m2 on days 1, 4, 8, 11 | 32% | Rise in hemoglobin >/ = 2 g/dL, transfusion independence | 16 months (observed) | Requires acyclovir prophylaxis |
| . | Dose . | Overall response rate . | Definition of response . | Median duration of response . | Clinical considerations . |
|---|---|---|---|---|---|
| Rituximab | 375 mg/m2 weekly × 4 | 45%-60% | CR: normalized hemoglobin level and absence of hemolysis or CAD symptoms; PR: hemoglobin increase ≥1-2 g/dL (varies by study), transfusion independence and improved CAD symptoms, 50% reduction in IgM concentration | 6.5-11 months (observed) | Risk of rituximab infusion reactions |
| Confirm vaccination status prior to dosing | |||||
| Months for effect | |||||
| Rituximab-fludarabine | Rituximab 375 mg/m2 on days 1, 29, 57, and 85 | 76% | CR: normalized hemoglobin level, absence of hemolysis, CAD symptoms, undetectable IgM, no evidence of clonal proliferation; PR: hemoglobin increase >/ = 2 g/dL, transfusion independence and improved CAD symptoms, 50% reduction in IgM concentration | >66 months (observed) | Risk of rituximab infusion reactions |
| Not appropriate for frail patients with comorbidities due to risk for infection, neutropenia | |||||
| Fludarabine 40 mg/m2 on days 1-5, 29-34, 57-61, and 85-89 | Months for effect | ||||
| Rituximab-bendamustine | Rituximab 375 mg/m2 q28 days × 4 | 71% | CR: normalized hemoglobin level, absence of hemolysis, CAD symptoms, undetectable IgM, no evidence of clonal proliferation; PR: hemoglobin increase >/ = 2 g/dL, transfusion independence and improved CAD symptoms, 50% reduction in IgM concentration | >32 months (observed) | Risk of rituximab infusion reactions |
| Not appropriate for frail patients with comorbidities due to risk for infection, neutropenia | |||||
| Bendamustine 90 mg/m2 on days 1, 2 q28 days × 4 | Months for effect | ||||
| Eculizumab | 600 mg weekly × 4, then 900 mg every other week through week 26 | 54% | Decrease in LDH level pre and post therapy >/ = 250 U/L | Must be used continuously to maintain effect | Rapid onset; may be used as a temporizing measure |
| Vaccinate against encapsulated bacteria; meningococcal prophylaxis until vaccinated | |||||
| Will not improve acrocyanosis | |||||
| Sutimlimab | 6500 mg weekly × 2, then every other week though 26 weeks | 54% | Hemoglobin increase >/ = 1.5 g/dL, transfusion independence, no use of CAD treatments | Must be used continuously to maintain effect | Rapid onset; may be used as a temporizing measure |
| Vaccinate against encapsulated bacteria; meningococcal prophylaxis until vaccinated | |||||
| Will not improve acrocyanosis | |||||
| Ibrutinib | 420 mg/d | 100% | CR: hemoglobin >12 g/dL; PR 10-12 g/dL or ≥2 g/dL | Studies reported on ~ median of 12 months daily use | Requires acyclovir prophylaxis |
| Useful for acrocyanosis | |||||
| Bortezomib | 1.3 mg/m2 on days 1, 4, 8, 11 | 32% | Rise in hemoglobin >/ = 2 g/dL, transfusion independence | 16 months (observed) | Requires acyclovir prophylaxis |
7500 mg for patients weighing >/ = 75 kg.
CR, complete response; PR, partial response.