Second malignancies in total therapy 2 and 3 for newly diagnosed multiple myeloma: influence of thalidomide and lenalidomide during maintenance.
Thalidomide and lenalidomide constitute an important part of effective myeloma therapy. Recent data from the Intergroup Francophone du Myélome, Cancer and Leukemia Group B, and Gruppo Italiano Malattie Ematologiche dell Adulto MM-015 trials suggest that lenalidomide maintenance therapy is associated with a higher incidence of second primary malignancies (SPMs), including both hematologic and solid malignancies. In the present study, we analyzed data from the Total Therapy 2 (TT2) trial, along with the 2 Total Therapy 3 (TT3) trials. TT2 patients were assigned randomly to either a control group (no thalidomide) or to the experimental group (thalidomide during induction, between transplantations, and during consolidation and maintenance). The 2 TT3 trials used thalidomide and bortezomib during induction, before and in consolidation after tandem melphalan-based transplantation; TT3A applied VTD (bortezomib, thalidomide, dexamethasone) in the first year of maintenance and TD for 2 more years, whereas TT3B used VRD (bortezomib, lenalidomide, dexamethasone) maintenance for 3 years. The cumulative incidence of SPMs did not differ significantly among the TT trial components when measured from enrollment (P = .78) or from initiation of maintenance (P = .82). However, a pairwise comparison of the TT2 arms suggested a lower incidence of hematologic SPMs in the thalidomide maintenance arm (hazard ratio = 0.38; P = .09). These trials are registered at www.clinicaltrials.gov as NCT00573391 (TT2), NCT00081939 (TT3A), and NCT00572169 (TT3B).
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. susmani@uams.edu
Saad Z
SZ
Usmani
Rachel
R
Sexton
Antje
A
Hoering
Christoph J
CJ
Heuck
Bijay
B
Nair
Sarah
S
Waheed
Yazan
Y
Al Sayed
Nabeel
N
Chauhan
Nisar
N
Ahmad
Shebli
S
Atrash
Nathan
N
Petty
Frits
F
van Rhee
John
J
Crowley
Bart
B
Barlogie
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D060828:Induction Chemotherapy; D000077269:Lenalidomide; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D011719:Pyrazines / Q000008:administration & dosage / Q000627:therapeutic use; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D000077269:Lenalidomide