Total therapy 2 without thalidomide in comparison with total therapy 1: role of intensified induction and posttransplantation consolidation therapies.
Patients with myeloma, treated on the thalidomide arm of total therapy 2 (TT2), had a higher complete response (CR) rate and improved event-free survival (EFS) but not overall survival (OS). To evaluate the benefit of TT2's posttandem autotransplant consolidation chemotherapy and dexamethasone maintenance, outcomes were compared on TT2 without thalidomide (n = 345; median follow-up, 3.5 years) and on predecessor trial TT1 (n = 231; median follow-up, 11.5 years). CR rates were similar (43% vs 41%); however, 5-year estimates of continuous CR (45% vs 32%, P < .001) and 5-year EFS (43% vs 28%, P < .001) were superior with TT2, with a trend for improved OS (62% vs 57%; P = .11). OS was also superior among patients achieving CR and receiving the second transplantation early after the first transplantation. Superior EFS and OS with TT2 versus TT1 was noted in the two thirds presenting without cytogenetic abnormalities (CAs); 4-year posttandem transplantation OS for patients with CAs was 47% with TT1 and 76% with TT2 when combination chemotherapy rather than DEX was applied for consolidation (P = .040). Thus, TT2 (without thalidomide) improved OS of patients without CAs; those with CAs benefited from posttransplantation consolidation chemotherapy. The favorable effects of CR and rapidly sequenced second transplantation attest to the validity of a melphalan dose-response effect in myeloma.
Barlogie
Bart
B
Medicine and Pathology, Myeloma Institute for Research & Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. barlogiebart@uams.edu
Tricot
Guido
G
Rasmussen
Erik
E
Anaissie
Elias
E
van Rhee
Frits
F
Zangari
Maurizio
M
Fassas
Athanasios
A
Hollmig
Klaus
K
Pineda-Roman
Mauricio
M
Shaughnessy
John
J
Epstein
Joshua
J
Crowley
John
J
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy*; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D013792:Thalidomide / Q000627:therapeutic use*; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D013792:Thalidomide; D003907:Dexamethasone