Evidence for cytogenetic and fluorescence in situ hybridization risk stratification of newly diagnosed multiple myeloma in the era of novel therapie.
Overall survival (OS) has improved with increasing use of novel agents in multiple myeloma (MM). However, the disease course remains highly variable, and the heterogeneity largely reflects different genetic abnormalities. We studied the impact of the Mayo risk-stratification model of MM on patient outcome in the era of novel therapies, evaluating each individual component of the model-fluorescence in situ hybridization (FISH), conventional cytogenetics (CG), and the plasma cell labeling index-that segregates patients into high- and standard-risk categories. This report consists of 290 patients with newly diagnosed MM, predominantly treated with novel agents, who were risk-stratified at diagnosis and were followed up for OS. Of these patients, 81% had received primarily thalidomide (n=50), lenalidomide (n=199), or bortezomib (n=79) as frontline or salvage therapies. Our retrospective analysis validates the currently proposed Mayo risk-stratification model (median OS, 37 months vs not reached for high- and standard-risk patients, respectively; P=.003). Although the FISH or CG test identifies a high-risk cohort with hazard ratios of 2.1 (P=.006) and 2.5 (P=.006), respectively, the plasma cell labeling index cutoff of 3% fails to independently prognosticate patient risk (hazard ratio, 1.4; P=.41). In those stratified as standard-risk by one of the 2 tests (FISH or CG), the other test appears to be of additional prognostic significance. This study validates the high-risk features defined by FISH and CG in the Mayo risk-stratification model for patients with MM predominantly treated with novel therapies based on immunomodulatory agents.
Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
Prashant
P
Kapoor
Rafael
R
Fonseca
S Vincent
SV
Rajkumar
Shirshendu
S
Sinha
Morie A
MA
Gertz
A Keith
AK
Stewart
P Leif
PL
Bergsagel
Martha Q
MQ
Lacy
David D
DD
Dingli
Rhett P
RP
Ketterling
Francis
F
Buadi
Robert A
RA
Kyle
Thomas E
TE
Witzig
Philip R
PR
Greipp
Angela
A
Dispenzieri
Shaji
S
Kumar
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D056747:Immunomodulation; D017404:In Situ Hybridization, Fluorescence; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D011719:Pyrazines / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D016879:Salvage Therapy; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D000077269:Lenalidomide