Future directions in multiple myeloma treatment.
Future therapy options for multiple myeloma may be directed at asymptomatic disease, as only symptomatic myeloma is treated currently. Additional genetic information from gene array analysis will mean that the identification of cases with poor prognosis will become more sophisticated. New markers are being discovered constantly, and these continuously change the picture regarding prognostic factors. More intensive treatment options increase the depth of remissions, thereby improving outcomes. In pilot studies, cyclophosphamide, thalidomide and dexamethasone (CTD) was a highly effective, well-tolerated regimen for patients refractory to initial therapy with VAD or with relapsed disease. It is being further evaluated as induction therapy in the current MRC Myeloma IX trial. Also under investigation is a small molecule derivative of thalidomide, CC-4047 (Actimid). It has between 1,000 and 10,000 times more potent antitumour necrosis factor alpha activity, with an additional immunomodulatory effect. It has been shown to be between 50 and 2,000 times more potent in the stimulation of T-cell proliferation and 50-100 times more potent in augmenting interleukin-2 and interferon-gamma production. With many possible approaches to study and work through, future strategies will revolve around exploration of the effectiveness of combinations that incorporate new agents in various disease and treatment settings. The use of genetic profiles to further delineate groups for different treatment approaches should enable the introduction of patient-specific treatment programmes in the future.
Child
J Anthony
JA
General Infirmary and University of Leeds, Leeds, UK. jachild@doctors.org.uk
Russell
Nigel
N
Sonneveld
Pieter
P
Schey
Steve
S
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic / Q000639:trends; D003520:Cyclophosphamide / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D018572:Disease-Free Survival; D004341:Drug Evaluation; D005544:Forecasting; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D012074:Remission Induction; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use
D014408:Biomarkers, Tumor; D007376:Interleukin-2; D013792:Thalidomide; D003907:Dexamethasone; D007371:Interferon-gamma; D003520:Cyclophosphamide; C467566:pomalidomide