title: Outcomes of primary refractory multiple myeloma and the impact of novel therapies.
abstract: Over the past decade, use of novel agents, including immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) has resulted in high response rates and improvement in overall survival (OS) for patients with multiple myeloma (MM); however, the prognostic significance of refractoriness to these agents when used as initial therapy has not been extensively studied. We reviewed the outcomes of 816 consecutive patients treated for MM at our institution since 2006 to evaluate the survival difference between those achieving at least a partial response (PR) to induction therapy and those who were primary refractory. The median OS from start of therapy was significantly shorter for the primary refractory group at 3.6 vs. 7.6 years for the responding patients (P < 0.001). The difference in median OS persisted when only patients receiving a novel agent as part of induction therapy were considered (3.6 vs. 7.9 years, P < 0.001) and in a 4-month landmark analysis (4.2 vs. 7.6 years, P < 0.001). The median OS for patients achieving a complete response (CR), very good partial response (VGPR), PR, or less than PR was not reached (NR), 6.1, 6.4, and 4.2 years from the 4-month landmark, respectively (P < 0.001). The comparatively poor outcomes of patients refractory to induction therapy in the current era of novel agents suggests that this high-risk subpopulation must be further studied for predictors of resistance and, when identified, should be targeted for clinical trials.
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Neil
authors.initials: N
authors.lastname: Majithia
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: S
authors.initials: S
authors.lastname: Vincent Rajkumar
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Francis K
authors.initials: FK
authors.lastname: Buadi
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Hayman
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: David
authors.initials: D
authors.lastname: Dingli
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kapoor
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hwa
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: John A
authors.initials: JA
authors.lastname: Lust
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Go
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Shaji K
authors.initials: SK
authors.lastname: Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D000069286:Bortezomib / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077269:Lenalidomide; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000401:mortality; D011241:Prednisone / Q000627:therapeutic use; D016016:Proportional Hazards Models; D061988:Proteasome Inhibitors / Q000627:therapeutic use*; D011859:Radiography; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D061988:Proteasome Inhibitors; D013792:Thalidomide; D000069286:Bortezomib; D004317:Doxorubicin; D003520:Cyclophosphamide; D000077269:Lenalidomide; D008558:Melphalan; D011241:Prednisone