title: Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: a meta-analysis.
abstract: Trials comparing efficacy of melphalan prednisone (MP) with MP plus thalidomide in transplant ineligible, elderly patients with multiple myeloma have provided conflicting evidence. Although there is agreement regarding improved response rates (RRs) and higher toxicity with the addition of thalidomide to MP, the impact on progression free survival (PFS) and overall survival (OS) is less clear. We performed a meta-analysis comparing efficacy of melphalan, prednisone and thalidomide (MPT) and MP by pooling results on RR, PFS and OS reported in all the identified randomized controlled trials (RCTs) under a random effects model. Overall, six prospective RCTs, with data extractable from five published trials (n=1571) [corrected] were identified. The pooled odds ratio of responding to therapy with MPT vs MP was 3.39 (P<0.001, 95% CI: 2.24-5.12). The pooled hazard ratios for PFS and OS were and 0.68 (P<0.001; 95% CI: 0.55-0.82) and 0.80 (P=0.07; 95% CI: 0.63-1.02), respectively, in favor of MPT. The odds ratios for high grade peripheral neuropathy and deep venous thrombosis were 6.6 and 2.4, respectively, in favour of MP. There was significant heterogeneity among the RCTs. Our meta-analysis demonstrates that in previously untreated, transplant ineligible, elderly myeloma patients, the addition of T to MP results in significantly improved RR and PFS with a trend towards improvement in OS compared with MP alone, but at a cost of significantly greater toxicity.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kapoor
authors.forename: S V
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: A
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: M A
authors.initials: MA
authors.lastname: Gertz
authors.forename: M Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: D
authors.initials: D
authors.lastname: Dingli
authors.forename: J R
authors.initials: JR
authors.lastname: Mikhael
authors.forename: V
authors.initials: V
authors.lastname: Roy
authors.forename: R A
authors.initials: RA
authors.lastname: Kyle
authors.forename: P R
authors.initials: PR
authors.lastname: Greipp
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: S J
authors.initials: SJ
authors.lastname: Mandrekar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage; D019737:Transplants; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D008558:Melphalan; D011241:Prednisone