title: Current and emerging triplet combination therapies for relapsed and refractory multiple myeloma.
abstract: Despite significant improvement in outcomes have been observed for multiple myeloma (MM) patients over the past 10-15 years, mainly due to the introduction of novel agents targeting the tumor clone and the bone marrow microenvironment, treatment of refractory and/or relapsed (RR) disease remains a challenge, particularly for patients who have failed prior bortezomib- and lenalidomide-based therapies. More recently, new drugs with different mechanisms of action, including second generation proteasome inhibitors, third generation immunomodulatory drugs, histone deacetylase inhibitors and monoclonal antibodies, have been developed and are under investigation, further increasing treatment options for RRMM patients. Overall, novel agent-based triplet combinations demonstrated superior response rates and prolonged disease control when compared with two-drug regimens in several randomized clinical trials, without adding any relevant additional toxicity. Salvage triplet therapies are likely to play a key role in overcoming drug-resistance and hold promise to further improve long-term outcomes of RRMM patients.
authors.affiliation: a "Seràgnoli" Institute of Hematology , Bologna University School of Medicine , Bologna , Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pantani
authors.affiliation: a "Seràgnoli" Institute of Hematology , Bologna University School of Medicine , Bologna , Italy.
authors.forename: A
authors.initials: A
authors.lastname: Brioli
authors.affiliation: a "Seràgnoli" Institute of Hematology , Bologna University School of Medicine , Bologna , Italy.
authors.forename: P
authors.initials: P
authors.lastname: Tacchetti
authors.affiliation: a "Seràgnoli" Institute of Hematology , Bologna University School of Medicine , Bologna , Italy.
authors.forename: B A
authors.initials: BA
authors.lastname: Zannetti
authors.affiliation: a "Seràgnoli" Institute of Hematology , Bologna University School of Medicine , Bologna , Italy.
authors.forename: K
authors.initials: K
authors.lastname: Mancuso
authors.affiliation: a "Seràgnoli" Institute of Hematology , Bologna University School of Medicine , Bologna , Italy.
authors.forename: S
authors.initials: S
authors.lastname: Rocchi
authors.affiliation: a "Seràgnoli" Institute of Hematology , Bologna University School of Medicine , Bologna , Italy.
authors.forename: M
authors.initials: M
authors.lastname: Martello
authors.affiliation: a "Seràgnoli" Institute of Hematology , Bologna University School of Medicine , Bologna , Italy.
authors.forename: I
authors.initials: I
authors.lastname: Rizzello
authors.affiliation: a "Seràgnoli" Institute of Hematology , Bologna University School of Medicine , Bologna , Italy.
authors.forename: C
authors.initials: C
authors.lastname: Terragna
authors.affiliation: a "Seràgnoli" Institute of Hematology , Bologna University School of Medicine , Bologna , Italy.
authors.forename: E
authors.initials: E
authors.lastname: Zamagni
authors.affiliation: a "Seràgnoli" Institute of Hematology , Bologna University School of Medicine , Bologna , Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cavo
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069286:Bortezomib / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D061988:Proteasome Inhibitors / Q000627:therapeutic use; D016879:Salvage Therapy; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D007155:Immunologic Factors; D061988:Proteasome Inhibitors; D013792:Thalidomide; D000069286:Bortezomib; D000077269:Lenalidomide
keywords: IMiDs; Multiple myeloma; monoclonal antibodies; proteasome inhibitors; relapsed refractory