title: Thalidomide, dexamethasone, Doxil and Velcade (ThaDD-V) followed by consolidation/maintenance therapy in patients with relapsed-refractory multiple myeloma.
abstract: In newly diagnosed multiple myeloma (MM), three/four-drug combinations as induction therapy seem to be more effective compared with two-drug associations in terms of response rate and duration of remission. Moreover, there is an emergent body of evidences that consolidation/maintenance therapy improves the quality of response and remission duration. However, the impact of these strategies in relapsed/refractory MM (r-rMM) is still unknown. This phase II study explored the four-drug combination of thalidomide, dexamethasone, pegylated liposomal doxorubicin (pLD), and bortezomib (ThaDD-V) as induction followed by consolidation therapy based on bortezomib-dexamethasone and thalidomide-dexamethasone and maintenance therapy with thalidomide in r-rMM patients. The primary end points of this study were best response and toxicity of the planned therapy. Forty-six patients were enrolled. At the end of therapy, the best response was as follows: 37% complete response (CR), 34.5% VGPR, and 4.5% PR with an ORR of 76%. Patients receiving ≤ 2 prior regimens had a CR rate significantly higher than those heavily treated (41% vs 0%; p=0.010). With a median follow-up of 31 months, median time to progression (TTP) and OS were 18.5 months and 40 months, respectively. By a 6-month landmark analysis, patients who completed the protocol had a significantly longer TTP compared with those who did not because of toxicity (not reached vs 7 months; p<0.0001). After the dose intensity of bortezomib was reduced due to an excess of peripheral neuropathy (PN), grade 3 PN occurred in 7.5% of patients. ThaDD-V followed by consolidation-maintenance therapy seems to be very effective in patients with r-rMM provided that this procedure is used early on relapse when very deep responses seem to be the rule.
authors: Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Via Conca, 71, 60020, Ancona, Italy. m.offidani@ospedaliriuniti.marche.it
authors: Massimo
authors: M
authors: Offidani
authors: Laura
authors: L
authors: Corvatta
authors: Claudia
authors: C
authors: Polloni
authors: Silvia
authors: S
authors: Gentili
authors: Anna
authors: A
authors: Mele
authors: Rita
authors: R
authors: Rizzi
authors: Massimo
authors: M
authors: Catarini
authors: Patrizia
authors: P
authors: Caraffa
authors: Arduino
authors: A
authors: Samori
authors: Nicola
authors: N
authors: Blasi
authors: Mario
authors: M
authors: Ferranti
authors: Lara
authors: L
authors: Malerba
authors: Marino
authors: M
authors: Brunori
authors: Pietro
authors: P
authors: Leoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D003907:Dexamethasone / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D011719:Pyrazines / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D013792:Thalidomide / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin