Table 1.

Management of adverse events in multiple myeloma patients treated with novel agents

Toxicity	Novel agent suspected to cause the event	How to manage the event	Dose-adjustment recommended
Neutropenia	Lenalidomide, Bortezomib	G-CSF until neutrophil recovery in case of uncomplicated grade 4 AE or grade 2-3 AEs complicated by fever or infection.	25% to 50% drug reduction
Thrombocytopenia	Bortezomib, Lenalidomide	Plate let transfusion in case of occurrence of grade 4 AE.	25% to 50% drug reduction
Anaemia	Bortezomib, Lenalidomide	Erythropoietin or darbepoietin if hemoglobin level is ≤ 10 g/dL.	25% to 50% drug reduction
Infection	All	Trimetoprin-cotrimoxazoie for Pneumocystis carinii prophylaxis during high-dose dexamethasone. Acyclovir or valacyclovir for HVZ prophylaxis during bortezomib-containing therapy.	25% to 50% drug reduction
Neurotoxicity	Bortezomib, Thalidomide	Neurological assessment before and during treatment. Prompt dose reduction is recommended	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.
Skin toxicity	Thalidomide, Lenalidomide	Steroids and antihistamines.	Interruption in case of grade 3-4 AE. 50% reduction in case of grade 2 AE.
Gastrointestinal toxicity	All	Appropriate diet, laxatives, physical exercise, hydration, antidiarrheics.	Interruption in case of grade 3-4 AEs 50% reduction in case of grade 2 AEs.
Thrombosis	Thalidomide, Lenalidomide	Aspirin 100-325 mg if no or one individual/myeloma thrombotic risk factor is present. LMWH orfull dose warfarin if there are two or more individual/myeloma risk factors and in all patients with thalidomide-related risk factors.	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 with dialysis required: 5 mg/day after dialysis on dialysis day.
Bone pain	None	Start with simple non-opioid analgesics. If no improvement is detected continue with weak opioid analgesics. In case of no relief, use synthetic opioids or strong (natural) opioids. Local radiotherapy is also an effective strategy.	–––––
Bone disease	None	Vetebropalsty (percutaneous injection of poiymethacryiate or equivalent material into the vertebral body). Use of balloon kyphoplasty enhances vertebral height. Long-term bisphosphonates may prevent bone disease. Further strategies are intravenous pamidronate, intravenous zoledronic acid as well as oral clodronate.	–––––