New Agents in Multiple Myeloma Treatment
The new agents used in multiple myeloma treatment include proteasome inhibitors, immunomodulatory and antiangiogenic agents, and monoclonal antibodies—making options a, d, and e correct. 1
Proteasome Inhibitors (Option A: CORRECT)
Second-generation proteasome inhibitors represent a major advance in myeloma therapy. 1
- Carfilzomib and ixazomib are approved second-generation proteasome inhibitors that have been incorporated into clinical guidelines and transformed treatment approaches 1
- These agents work by inhibiting the 26S proteasome, which is critical for myeloma cell pathogenesis and proliferation 2
- Ixazomib is the first oral proteasome inhibitor, offering improved convenience compared to intravenous bortezomib 1
- The Mayo Clinic recommends carfilzomib-based regimens (KRd, KPd) and ixazomib-based regimens (IRd, ICd) as standard options for relapsed disease 1
Immunomodulatory and Antiangiogenic Agents (Option D: CORRECT)
Third-generation immunomodulatory drugs with antiangiogenic properties are established new agents. 1
- Pomalidomide is a third-generation IMiD that has been approved and incorporated into clinical guidelines 1
- These agents interrupt myeloma-stromal cell interactions in the bone marrow microenvironment and possess antiangiogenic properties 3
- The American Society of Clinical Oncology recommends pomalidomide-based regimens for dual-refractory patients 4, 5
- IMiDs work through multiple mechanisms including direct apoptosis induction and disruption of cytokines with angiogenic properties 3
Monoclonal Antibodies (Option E: CORRECT)
Monoclonal antibodies represent an entirely new class of agents that have revolutionized myeloma treatment. 1
- Daratumumab (anti-CD38) and elotuzumab (anti-SLAMF7) were approved and have transformed treatment approaches 1
- The International Myeloma Society recommends daratumumab-lenalidomide-dexamethasone (DRd) as primary treatment for lenalidomide-sensitive first relapse, providing median progression-free survival of 45 months 4
- Elotuzumab is approved in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone 6
- Isatuximab (anti-CD38) and belantamab mafodotin (BCMA-targeted antibody-drug conjugate) are additional monoclonal antibody-based therapies 7
Tyrosine Kinase Inhibitors (Option B: INCORRECT)
Tyrosine kinase inhibitors are not established agents in multiple myeloma treatment. The guideline evidence from Blood and Mayo Clinic Proceedings does not list tyrosine kinase inhibitors among the approved classes of agents for myeloma 1
Anti-JAK2 Agents (Option C: INCORRECT)
Anti-JAK2 agents are not used in multiple myeloma treatment. These agents are relevant for myeloproliferative neoplasms, not myeloma. The comprehensive guideline reviews do not include JAK2 inhibitors among the six established drug classes (alkylators, steroids, PIs, IMiDs, DACIs, and mAbs) 1
Clinical Context
The availability of at least six different classes of agents that can be combined in doublet or triplet regimens has led to median overall survival approaching 6-10 years 1. The International Myeloma Society recommends triplet regimens containing at least two drug classes that patients are not refractory to for optimal outcomes 4.