Table 1. Investigational drugs with significant single-agent activity in multiple myeloma.

Agent	Dosing schedule used in clinical trials	Postulated mechanism of action	Side effects
Isatuximab20	20 mg kg−1 weekly × 4, followed by maintenance therapy of 10 mg kg−1 IV Q2W	Monoclonal antibody targeting CD38	Infusion-related reactions, anemia, thrombocytopenia, fatigue, nausea
Marizomib24	0.5 mg m−2 IV over 2 h, Days 1, 4, 8 and 11 of a 21-day cycle	Inhibits the ubiquitin–proteasome catalytic pathway in cells by binding directly with the 20S proteasome complex	Dizziness, fever, fatigue, nausea, hallucinations
Oprozomib26	240 mg per day once daily, Days 1, 2, 8 and 9 of a 14-day cycle (+30 mg increments as tolerated to max 300 mg per day) OR 150 mg per day once daily Days 1–5 of a 14-day cycle (+30 mg increments as tolerated to max 180 mg per day)	Inhibits the ubiquitin–proteasome catalytic pathway in cells by binding directly with the 20S proteasome complex	Hypotension, thrombocytopenia, anemia, diarrhea, vomiting, nausea
Venetoclax40	1200 mg PO once daily (after a 2-week dose ramp-up)	Inhibits Bcl-2, a well-known regulator of apoptosis	Neutropenia, thrombocytopenia, anemia, fatigue, nausea
Dinaciclib30	50 mg m−2 IV infusion over 2 h, Day 1 of a 21-day cycle for a maximum of 12 cycles	Inhibits CDK in the cell cycle	Leukopenia, thrombocytopenia, fatigue, gastrointestinal side effects
Filanesib38	1.5 mg m−2 IV, Days 1, 2, 15 and 16 of a 28-day cycle	Inhibits KSP and thereby cell division	Neutropenia, thrombocytopenia, anemia, fatigue
LGH447(ref. 47)	500 mg PO once daily	Inhibits PIM kinase, which acts to regulate and express cell cycle progression and survival	Neutropenia, thrombocytopenia, anemia

Abbreviations: CDK, cyclin-dependent kinase; IV, intravenous; KSP, kinesin spindle protein; PIM kinase, proto-oncogene serine/threonine-protein kinase; PO, per ora.