Suzanne Lentzsch1, Galina G Lagos1, Raymond L Comenzo2, Jeffrey A Zonder3, Keren Osman4, Samuel Pan1, Divaya Bhutani1, Silva Pregja3, Vaishali Sanchorawala5, Heather Landau6. 1. Division of Hematology/Oncology, Columbia University Medical Center, New York, NY. 2. Division of Hematology/Oncology, Tufts Medical Center, Boston, MA. 3. Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI. 4. Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY. 5. Amyloidosis Center, Boston University School of Medicine and Boston Medical Center, Boston, MA. 6. Division of Hematologic Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
Abstract
PURPOSE: No established treatments exist for relapsed/refractory systemic light-chain (AL) amyloidosis. Bendamustine has shown potential in the treatment of multiple myeloma. We conducted a phase II, multicenter trial to assess the efficacy and safety of bendamustine with dexamethasone (ben-dex) in patients with persistent or progressive AL amyloidosis after ≥ 1 prior therapy. METHODS: The trial enrolled 31 patients who received bendamustine on days 1 and 2 (100 mg/m2 intravenously) with 40 mg of weekly dexamethasone in 28-day cycles until disease progression or up to 6 cycles after complete hematologic response. The primary objective was the rate of partial hematologic response (PR) or better. RESULTS: Patients received a median of 4 cycles (range, 2-12 cycles) with 57% of patients achieving a PR or better (11% complete response, 18% very good PR). The overall organ response was 29% among the 24 patients who had measurable organ involvement. Treatment was well tolerated with no grade 5 treatment-related adverse events (AEs). Sixty-five percent of patients had a therapy-related grade 3-4 AE. The most common AEs included myelosuppression, fatigue, and nausea/vomiting. The median overall survival was 18.2 months (95% CI, 11.3 to 43.8 months), and hematologic response was associated with prolonged survival (P = .0291). The median progression-free survival was 11.3 months (95% CI, 5.0 to 15.4 months). CONCLUSION: Overall, ben-dex is a viable treatment option with substantial efficacy and limited toxicity for patients with pretreated AL amyloidosis who have limited therapeutic options. This trial was registered at (ClinicalTrials.gov identifier: NCT01222260).
PURPOSE: No established treatments exist for relapsed/refractory systemic light-chain (AL) amyloidosis. Bendamustine has shown potential in the treatment of multiple myeloma. We conducted a phase II, multicenter trial to assess the efficacy and safety of bendamustine with dexamethasone (ben-dex) in patients with persistent or progressive AL amyloidosis after ≥ 1 prior therapy. METHODS: The trial enrolled 31 patients who received bendamustine on days 1 and 2 (100 mg/m2 intravenously) with 40 mg of weekly dexamethasone in 28-day cycles until disease progression or up to 6 cycles after complete hematologic response. The primary objective was the rate of partial hematologic response (PR) or better. RESULTS:Patients received a median of 4 cycles (range, 2-12 cycles) with 57% of patients achieving a PR or better (11% complete response, 18% very good PR). The overall organ response was 29% among the 24 patients who had measurable organ involvement. Treatment was well tolerated with no grade 5 treatment-related adverse events (AEs). Sixty-five percent of patients had a therapy-related grade 3-4 AE. The most common AEs included myelosuppression, fatigue, and nausea/vomiting. The median overall survival was 18.2 months (95% CI, 11.3 to 43.8 months), and hematologic response was associated with prolonged survival (P = .0291). The median progression-free survival was 11.3 months (95% CI, 5.0 to 15.4 months). CONCLUSION: Overall, ben-dex is a viable treatment option with substantial efficacy and limited toxicity for patients with pretreated AL amyloidosis who have limited therapeutic options. This trial was registered at (ClinicalTrials.gov identifier: NCT01222260).
Authors: Gregory P Kaufman; Stanley L Schrier; Richard A Lafayette; Sally Arai; Ronald M Witteles; Michaela Liedtke Journal: Blood Date: 2017-06-14 Impact factor: 22.113
Authors: Paolo Milani; Stefan Schönland; Giampaolo Merlini; Christoph Kimmich; Andrea Foli; Tobias Dittrich; Marco Basset; Carsten Müller-Tidow; Tilmann Bochtler; Giovanni Palladini; Ute Hegenbart Journal: Blood Date: 2018-08-14 Impact factor: 22.113
Authors: Juliane Beck; Andreas Schwarzer; Dietrich Gläser; Lars-Olof Mügge; Jens Uhlig; Simone Heyn; Brigitte Kragl; Martin Mohren; Franz Albert Hoffmann; Thoralf Lange; Thomas Schliwa; Thomas Zehrfeld; Cornelia Becker; Ute Kreibich; Cornelia Winkelmann; Thomas Edelmann; Marc Andrea; Marius Bill; Madlen Jentzsch; Sebastian Schwind; Dietger Niederwieser; Wolfram Pönisch Journal: J Cancer Res Clin Oncol Date: 2017-08-21 Impact factor: 4.553
Authors: Umit Tapan; David C Seldin; Kathleen T Finn; Salli Fennessey; Anthony Shelton; Jerome B Zeldis; Vaishali Sanchorawala Journal: Blood Date: 2010-12-02 Impact factor: 22.113
Authors: Angela Dispenzieri; Francis Buadi; Kristina Laumann; Betsy LaPlant; Suzanne R Hayman; Shaji K Kumar; David Dingli; Steven R Zeldenrust; Joseph R Mikhael; Robert Hall; S Vincent Rajkumar; Craig Reeder; Rafael Fonseca; P Lief Bergsagel; A Keith Stewart; Vivek Roy; Thomas E Witzig; John A Lust; Stephen J Russell; Morie A Gertz; Martha Q Lacy Journal: Blood Date: 2012-04-04 Impact factor: 22.113
Authors: James R Berenson; Ori Yellin; Alberto Bessudo; Ralph V Boccia; Stephen J Noga; Donald S Gravenor; Dipti Patel-Donnelly; Robert S Siegel; Tarun Kewalramani; Edward J Gorak; Youram Nassir; Regina A Swift; Debra Mayo Journal: Br J Haematol Date: 2012-11-15 Impact factor: 6.998
Authors: M Offidani; L Corvatta; L Maracci; A M Liberati; S Ballanti; I Attolico; P Caraffa; F Alesiani; T Caravita di Toritto; S Gentili; P Tosi; M Brunori; D Derudas; A Ledda; A Gozzetti; C Cellini; L Malerba; A Mele; A Andriani; S Galimberti; P Mondello; S Pulini; U Coppetelli; P Fraticelli; A Olivieri; P Leoni Journal: Blood Cancer J Date: 2013-11-22 Impact factor: 11.037