Table 2.

Multiple myeloma therapy overview.

Class	Drug	Dosing/Administration	Renal/Hepatic Considerations	Adverse Reactions	Clinical Pearls	Hypersensitivity Reactions
IMiDs [7, 8, 9]	Thalidomide (Thalomid)	•50–200 mg by mouth daily continuously in evening at least 1 h after evening meal (200 mg usual starting dose)	•No specific recommendations	•Birth defects/fetal death •VTE •Peripheral neuropathy •Constipation •Sedation	•VTE prophylaxis required •REMS program present •Taken continuously without breaks	Not applicable
	Lenalidomide (Revlimid or Generic Equivalent)	•2.5–25 mg by mouth with or without food days 1–21 every 28d (25 mg usual starting dose)	•Renal: dose adjustments vary depending on indication for CrCl <60 mL/min	•Birth defects/fetal death •VTE •Cytopenias •Peripheral neuropathy •Pruritus, skin rash •Diarrhea, constipation •Muscle spasms	•VTE prophylaxis required •REMS program present •7-day treatment free period in induction regimens to allow for WBC count recovery	Not applicable
	Pomalidomide (Pomalyst)	•1–4 mg by mouth with or without food days 1–21 every 28d (4 mg usual starting dose)	•Renal: reduce dose to 3 mg with hemodialysis patients or if CrCl <15 mL/min •Hepatic: reduce dose to 3 mg for Child-Pugh A or B; reduce dose to 2 mg for Child-Pugh C	•Birth defects/fetal death •VTE •Cytopenias •Peripheral neuropathy •Pruritus, skin rash •Diarrhea, constipation	•VTE prophylaxis required •REMS program present •7-day treatment free period in induction regimens to allow for WBC count recovery	Not applicable
PIs [10, 11, 12]	Bortezomib (Velcade)	•1.3 mg/m2 SQ d1, 4, 8, 11 every 21d OR 1.3 mg/m2 d1, 8, 15, 22 every 28d	•Hepatic: reduce starting dose to 0.7 mg/m2 for total bilirubin >1.5x ULN; may consider dose escalation to 1 mg/m2 in subsequent cycles depending on tolerability	•Thrombocytopenia •Hepatotoxicity •Peripheral neuropathy •Diarrhea, constipation	•Consecutive doses should be separated by at least 72 h •Less peripheral neuropathy with SQ route of administration •HSV/VZV viral prophylaxis required	Not applicable
	Carfilzomib (Kyprolis)	•Once-weekly scheme: (cycle 1) 20 mg/m2 IV d1, 70 mg/m2 d8, 15; (subsequent cycles) 70 mg/m2 d1, 8, 15 every 28d •Twice-weekly scheme: (cycle 1) 20 mg/m2 IV d1, 2 then 36 mg/m2 d8, 9, 15, 16 every 28d; (subsequent cycles) 36 mg/m2 d1, 2, 8, 9, 15, 16 every 28d	•Hepatic: reduce dose by 25% for total bilirubin of > 1–3x ULN with any AST or for any AST > ULN; no recommendations provided for total bilirubin of >3 x ULN	•TLS •Cardiotoxicity (heart failure) •Pulmonary complications •Peripheral neuropathy •Cytopenias	•Hydration with 250–500 mL of IV fluid recommended prior to each dose of cycle 1 due to TLS risk; allopurinol not routinely recommended •Administer dexamethasone 30 min to 4 h prior to each carfilzomib dose; counsel patients to take their treatment dexamethasone dose prior to their infusion appointment •Baseline echocardiogram not required but recommended •HSV/VZV viral prophylaxis required	•Reinstate dexamethasone premedication. •No specific recommendations on infusion rate restart
	Ixazomib (Ninlaro)	•4 mg PO d1, 8, 15 every 28d	•Hepatic: reduce starting dose to 3 mg in patients with total bilirubin >1.5–3x •Renal: reduce starting dose to 3 mg in CrCl <30 mL/min or ESRD	•GI toxicities •Peripheral neuropathy •Peripheral edema •Cutaneous reactions •Hepatotoxicity •Cytopenias	•Take on an empty stomach •HSV/VZV viral prophylaxis required	•Not applicable
Monoclonal Antibodies [13, 14,15, 16, 17]	Elotuzumab (Empliciti)	With lenalidomide: •C1-2: 10 mg/kg IV d1, 8, 15, 22 •C2 onwards: 10 mg/kg IV d1, 15 With pomalidomide: •C1-2: 10 mg/kg IV d1, 8, 15, 22 •C2 onwards: 20 mg/kg IV d1	•Hepatic (transaminitis grade 3 or higher): withhold therapy until resolution	•Hypersensitivity reactions •Infections •Second primary malignancies •Hepatotoxicity •Interference with M-protein	•Premedicate with dexamethasone, acetaminophen, H1RA, and H2RA; 8–28 mg of total weekly dexamethasone dose should be given 3–24 h prior to elotuzumab depending on target weekly dexamethasone dose (see package insert for full details) •Infusion rate titrated based on tolerability	•Upon resolution to Grade 1, restart at 0.5 mL/min and gradually increase at a rate of 0.5 mL/min every 30 min as tolerated to the rate at which the hypersensitivity reaction occurred. Resume escalation if there is no recurrence of reaction.
	Daratumumab (Darzalex[IV] or Darzalex Faspro [SQ])	•C1: 8 mg/kg IV d1, 2, 16 mg/kg IV d8, 15, 22 •C2: 16 mg/kg IV d1, 8, 15, 22 •C3-6: 16 mg/kg IV d1, 15 •C7 onwards: 16 mg/kg IV monthly	•No specific recommendations	•Hypersensitivity reactions •Hypertension •Upper and lower respiratory tract infections, cough, bronchitis	•HSV/VZV viral prophylaxis required •Premedicate with dexamethasone, acetaminophen, and H1RA. Montelukast optional. •Infusion rate titrated based on tolerability •May cause false positive reactions in indirect antiglobulin tests (Coombs' test); obtain RBC type and screen prior to first dose	•For daratumumab: •Once reaction symptoms resolve, consider restarting the infusion at no more than half the rate at which the reaction occurred. •Future cycles initiated at 50 mL/h. •For daratumumab and hyaluronidase-fihj: •Pause or slow down delivery rate if the patient experiences pain. In the event pain is not alleviated by pausing or slowing down delivery rate, a second injection site may be chosen on the opposite side of the abdomen to deliver the remainder of the dose.
	Isatuximab-irfc (Sarclisa)	•C1: 10 mg/kg IV d1, 8, 15, 22 •C2 onwards: 10 mg/kg IV d1, 15	•No specific recommendations	•Hypersensitivity reactions •Hypertenstion •Upper and lower respiratory infections, dyspnea •Neutropenia	•HSV/VZV viral prophylaxis required •Premedicate with dexamethasone, acetaminophen, H1RA, and H2RA •Infusion rate titrated based on tolerability •May cause false positive reactions in indirect antiglobulin tests (Coombs' test); obtain RBC type and screen prior to first dose	•If symptoms improve, restart at half the initial rate, with supportive care and close monitoring. •If symptoms do not recur after 30 min, the rate may be increased to the initial rate, and then increased incrementally.
	Belantamab mafodotin-blmf (Blenrep)	•2.5 mg/kg IV every 21d	•No specific recommendations	•Ocular toxicity- blurred vision, keratitis, photophobia •Fevers •Thrombocytopenia	•REMS program: routine eye exams required (baseline, prior to each dose, and for worsening ocular symptoms) •Use of preservative-free lubricating eye drops four times daily during therapy recommended •Avoid contact lenses if possible	•If grade 2 or worse, stop the infusion and provide supportive care. Once symptoms resolve, resume at lower infusion rate, at least reduced by 50%.
Miscellaneous [18, 19]	Selinexor (Xpovio)	With dexamethasone: •80 mg by mouth d1-3 every 7d (with or without food) With bortezomib and dexamethasone: •100 mg by mouth every 7d	•No specific recommendations	•Thrombocytopenia •Neutropenia •GI toxicity •Hyponatremia •Neurological toxicity	•Associated with moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Administer a 5-HT3 antagonist and other antiemetics as clinically appropriate)	•Not applicable
	Venetoclax (Venclexta)	•800 mg once daily	•Hepatic: reduce the daily venetoclax dose by 50% for severe impairment (Child-Pugh class C) •Renal: no specific recommendations	•Edema •Skin rash •Electrolyte disorder •Anemia •Leukopenia •Neutropenia •Thrombocytopenia •Hepatotoxicity •Upper respiratory tract infection	•Associated with many drug-drug interactions including CYP3A4 inducers & inhibitors and P-glycoprotein inhibitors (may constitute dose reductions)	•Not applicable

Abbreviations: CrCl: creatinine clearance, ESRD: end-stage renal disease, GI: gastrointestinal, H1RA: histamine type 1 receptor antagonist; H2RA: histamine type 2 receptor antagonist, HSV/VZV: herpes simplex virus/varicella zoster virus, IMiDs: immunomodulators, PIs: proteosome inhibitors, LFTs: liver function tests, RBC: red blood cell, REMS: risk evaluation and mitigation strategy, SCr: serum creatinine, TLS: tumor lysis syndrome, VTE: venous thromboembolism, ULN: upper limit of normal, WBC: white blood cell.