title: Primary failure of bortezomib in newly diagnosed multiple myeloma--understanding the magnitude, predictors, and significance.
abstract: Botezomib-based induction is highly effective for the treatment of newly diagnosed multiple myeloma (NDMM). We investigated the outcomes of NDMM patients who failed to respond to bortezomib-based induction in a 'real-life' clinical setting. In a cohort of 295 consecutive NDMM patients in 3 medical centers, 74 (25%) failed to achieve at least partial response after 4 induction cycles, and were classified as non-responsive. Compared to induction responders, they were older, more frequently anemic, had a higher incidence of del17p and ISS-3, and a worse performance status. In multivariable analysis, bortezomib-based induction failure occurred in 25% of patients and was the strongest independent factor predicting mortality with a 5-fold hazard ratio (95% CI 1.44-8.68). Three-year overall survival in responsive vs. non-responsive patients were 76% vs. 53%, respectively (p < 0.0001). Survival from time of salvage second-line treatment was significantly shorter among induction non-responders vs. responders (25 months vs. not-reached, p = 0.024).
authors.affiliation: a Department of Hematology , Sourasky Medical Center and Tel Aviv University , Tel Aviv , Israel ;
authors.forename: Yael C
authors.initials: YC
authors.lastname: Cohen
authors.affiliation: a Department of Hematology , Sourasky Medical Center and Tel Aviv University , Tel Aviv , Israel ;
authors.forename: Erel
authors.initials: E
authors.lastname: Joffe
authors.affiliation: b Department of Hematology , Rambam Medical Center , Technion , Israel ;
authors.forename: Noam
authors.initials: N
authors.lastname: Benyamini
authors.affiliation: c Department of Clinical Therapeutics , National & Kapodistrian University of Athens School of Medicine , Athens , Greece.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: c Department of Clinical Therapeutics , National & Kapodistrian University of Athens School of Medicine , Athens , Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.affiliation: a Department of Hematology , Sourasky Medical Center and Tel Aviv University , Tel Aviv , Israel ;
authors.forename: Svetlana
authors.initials: S
authors.lastname: Trestman
authors.affiliation: b Department of Hematology , Rambam Medical Center , Technion , Israel ;
authors.forename: Viki
authors.initials: V
authors.lastname: Held-Kuznetsov
authors.affiliation: a Department of Hematology , Sourasky Medical Center and Tel Aviv University , Tel Aviv , Israel ;
authors.forename: Irit
authors.initials: I
authors.lastname: Avivi
authors.affiliation: c Department of Clinical Therapeutics , National & Kapodistrian University of Athens School of Medicine , Athens , Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010266:Paraproteins; D011379:Prognosis; D016016:Proportional Hazards Models; D012074:Remission Induction; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010266:Paraproteins; D000069286:Bortezomib
keywords: Bortezomib; induction; myeloma; resistance; survival