Management of adverse events in patients with multiple myeloma treated with novel agents.
| . | Suspected antimyeloma agent . | Management . | Dose modification . |
|---|---|---|---|
| G-CSF indicates granulocyte colony-stimulating factor; HVZ, herpes-varicella-zooster; LMWH, low-molecular-weight heparin. | |||
| Hematologic toxicity | |||
| Neutropenia | Lenalidomide and combinations | G-CSF until neutrophil recovery in case of uncomplicated grade 4 toxicity or grade 2–3 adverse events complicated by infection | 25%–50% reduction |
| Thrombocytopenia | Bortezomib, lenalidomide, and combinations | Platelet transfusion if grade 4 adverse events | 25%–50% reduction in case of grade 3–4 adverse event |
| Anemia | Bortezomib, lenalidomide, and combinations | Erythropoietin or darbepoietin in case of hemoglobin concentration ≤ 10 g/dL | 25%–50% reduction in case of grade 3–4 adverse event |
| Extra-hematologic toxicity | |||
| Infection | All the agents | Trimetoprin-cotrimoxazole for Pneumocystis carinii prophylaxis during high-dose dexamethasone. Acyclovir or valacyclovir for HVZ prophylaxis during bortezomib- based therapy | 25%–50% reduction in case of grade 3–4 adverse event |
| Neurotoxicity | Bortezomib, thalidomide, and combinations | Neurological assessment before and during treatment. Consider symptomatic treatment with gabapentin, pregabalin, vitamin B complex compounds, amitryptilin or L-carnitina (uncontrolled trials) | Bortezomib: 25%–50% reduction for grade 1 with pain or grade 2 peripheral neuropathy; dose interruption until peripheral neuropathy resolves to grade 1 or better with restart at 50% dose reduction for grade 2 with pain or grade 3 peripheral neuropathy; treatment discontinuation for grade 4 peripheral neuropathy. Thalidomide: 50% reduction for grade 2 neuropathy; discontinuation for grade 3; resume Thalidomide at a decreased dose if neuropathy improves to grade 1 |
| Cutaneous toxicity | Thalidomide, lenalidomide and combinations | Steroids and antihistamines | Interruption in case of grade 3–4 adverse events. 50% reduction in case of grade 2 adverse events. |
| Gastrointestinal toxicity | Thalidomide, bortezomib, and combinations | Appropriate diet, laxatives, exercise, hydration, antidiarrheic drugs | Interruption in case of grade 3–4 adverse events. 50% reduction in case of grade 2 adverse events. |
| Thrombosis | Thalidomide, lenalidomide, and combinations | Aspirin 100–325 mg if no or one individual/myeloma thrombotic risk factor is present. LMWH or full-dose warfarin if two or more individual/myeloma risk factors are present and in all patients who receive high-dose dexamethasone or doxorubicin or multiagent chemotherapy | Drug temporary interruption and full anticoagulation, then resume treatment. |
| Renal toxicity | Lenalidomide | Correct precipitant factors (dehydration, hypercalcemia, hyperuricemia, urinary infections, and concomitant use of nephrotoxic drugs) | Reduce dose according to creatinine clearance: if 30–60 mL/min: 10 mg/day, if < 30 mL/min without dialysis needing: 15 mg every other day; if < 30 mL/min and dialysis: 5 mg/day after dialysis on dialysis day |
| . | Suspected antimyeloma agent . | Management . | Dose modification . |
|---|---|---|---|
| G-CSF indicates granulocyte colony-stimulating factor; HVZ, herpes-varicella-zooster; LMWH, low-molecular-weight heparin. | |||
| Hematologic toxicity | |||
| Neutropenia | Lenalidomide and combinations | G-CSF until neutrophil recovery in case of uncomplicated grade 4 toxicity or grade 2–3 adverse events complicated by infection | 25%–50% reduction |
| Thrombocytopenia | Bortezomib, lenalidomide, and combinations | Platelet transfusion if grade 4 adverse events | 25%–50% reduction in case of grade 3–4 adverse event |
| Anemia | Bortezomib, lenalidomide, and combinations | Erythropoietin or darbepoietin in case of hemoglobin concentration ≤ 10 g/dL | 25%–50% reduction in case of grade 3–4 adverse event |
| Extra-hematologic toxicity | |||
| Infection | All the agents | Trimetoprin-cotrimoxazole for Pneumocystis carinii prophylaxis during high-dose dexamethasone. Acyclovir or valacyclovir for HVZ prophylaxis during bortezomib- based therapy | 25%–50% reduction in case of grade 3–4 adverse event |
| Neurotoxicity | Bortezomib, thalidomide, and combinations | Neurological assessment before and during treatment. Consider symptomatic treatment with gabapentin, pregabalin, vitamin B complex compounds, amitryptilin or L-carnitina (uncontrolled trials) | Bortezomib: 25%–50% reduction for grade 1 with pain or grade 2 peripheral neuropathy; dose interruption until peripheral neuropathy resolves to grade 1 or better with restart at 50% dose reduction for grade 2 with pain or grade 3 peripheral neuropathy; treatment discontinuation for grade 4 peripheral neuropathy. Thalidomide: 50% reduction for grade 2 neuropathy; discontinuation for grade 3; resume Thalidomide at a decreased dose if neuropathy improves to grade 1 |
| Cutaneous toxicity | Thalidomide, lenalidomide and combinations | Steroids and antihistamines | Interruption in case of grade 3–4 adverse events. 50% reduction in case of grade 2 adverse events. |
| Gastrointestinal toxicity | Thalidomide, bortezomib, and combinations | Appropriate diet, laxatives, exercise, hydration, antidiarrheic drugs | Interruption in case of grade 3–4 adverse events. 50% reduction in case of grade 2 adverse events. |
| Thrombosis | Thalidomide, lenalidomide, and combinations | Aspirin 100–325 mg if no or one individual/myeloma thrombotic risk factor is present. LMWH or full-dose warfarin if two or more individual/myeloma risk factors are present and in all patients who receive high-dose dexamethasone or doxorubicin or multiagent chemotherapy | Drug temporary interruption and full anticoagulation, then resume treatment. |
| Renal toxicity | Lenalidomide | Correct precipitant factors (dehydration, hypercalcemia, hyperuricemia, urinary infections, and concomitant use of nephrotoxic drugs) | Reduce dose according to creatinine clearance: if 30–60 mL/min: 10 mg/day, if < 30 mL/min without dialysis needing: 15 mg every other day; if < 30 mL/min and dialysis: 5 mg/day after dialysis on dialysis day |