Multiple Myeloma
A cancer of plasma cells in bone marrow, the second most common blood cancer. Proteasome inhibitors bortezomib and carfilzomib are cornerstone treatments. Motixafortide (CXCR4 antagonist) mobilises stem cells for autologous transplant in myeloma patients.
Technical Context
Myeloma pathophysiology: malignant plasma cells accumulate in bone marrow → monoclonal protein (M-protein/paraprotein) production → organ damage (CRAB criteria: Calcium elevation, Renal insufficiency, Anaemia, Bone lesions). Treatment evolution: pre-2000 (melphalan/prednisone, median survival 3 years) → 2003+ (bortezomib/Velcade — first proteasome inhibitor, combined with immunomodulatory drugs and dexamethasone, median survival increased to 5-7 years) → current era (quadruplet combinations including anti-CD38 antibody + proteasome inhibitor + IMiD + dexamethasone, with ASCT consolidation; median survival approaching 10+ years). Bortezomib mechanism: reversible 20S proteasome inhibition → accumulation of pro-apoptotic proteins + NF-κB suppression → myeloma cell apoptosis. Carfilzomib (Kyprolis): irreversible proteasome inhibition with greater selectivity — for relapsed/refractory disease. Motixafortide's role: CXCR4 antagonist mobilising HSCs for autologous stem cell transplant, which remains a key component of myeloma therapy for eligible patients.