title: Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma.
abstract: Comprehensive recommendations for maintenance therapy after autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to the safety and efficacy of this agent compared with lenalidomide in the post-ASCT setting are limited. Therefore, we retrospectively analyzed the outcomes of 102 patients with MM who received maintenance therapy with bortezomib after ASCT at Duke University's adult bone marrow transplant clinic between 2005 and 2015. Maintenance with bortezomib was initiated between 60 and 90 days after ASCT as a single agent 1.3 mg/m2once every 2 weeks (n = 92) or in combination with lenalidomide (10 mg/day) (n = 10). The median age at ASCT was 64 (range, 31 to 78). Of the 99 patients with molecular data available, 42% had high-risk cytogenetics (including d17p, t(4;14), +1q, and t(14;16) by fluorescein in situ hybridization). Overall, 46% of patients experienced side effects from maintenance therapy, with 31% of all patients experiencing peripheral neuropathy. In total, 2% of patients required discontinuation of bortezomib maintenance because of adverse events. No secondary malignancies were reported from the therapy. The median progression-free survival (PFS) for patients receiving maintenance therapy with bortezomib after ASCT was 36.5 months (95% confidence interval [CI], 21.3 to not available) and median overall survival was 72.7 months (95% CI, 63.9 to not available). The PFS of patients with high-risk cytogenetics was not statistically significantly different from those with standard-risk cytogenetics, suggesting that maintenance with bortezomib may help overcome the impact of high-risk cytogenetics on early progression. These results indicate that maintenance therapy with bortezomib represents a safe, well-tolerated, and efficacious option for patients with high-risk cytogenetics, renal insufficiency, an inability to tolerate lenalidomide, or a previous history of another cancer.
authors.affiliation: Division of Cellular Therapy, Duke University, Durham, North Carolina. Electronic address: Dharshan.sivaraj@duke.edu.
authors.forename: Dharshan
authors.initials: D
authors.lastname: Sivaraj
authors.affiliation: Division of Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Green
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Sung
authors.affiliation: Division of Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sarantopoulos
authors.affiliation: Division of Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Division of Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: Gwynn D
authors.initials: GD
authors.lastname: Long
authors.affiliation: Division of Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Horwitz
authors.affiliation: Division of Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Lopez
authors.affiliation: Division of Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Sullivan
authors.affiliation: Division of Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
authors.affiliation: Division of Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
authors.affiliation: Division of Cellular Therapy, Duke University, Durham, North Carolina.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004341:Drug Evaluation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy; D061988:Proteasome Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D061988:Proteasome Inhibitors; D013792:Thalidomide; D000069286:Bortezomib; D000077269:Lenalidomide
keywords: Autologous stem cell transplantation; Bortezomib; Maintenance therapy; Multiple myeloma