Rita Fazzi1, Iacopo Petrini2, Nicola Giuliani3, Riccardo Morganti4, Giovanni Carulli1, Benedetta Dalla Palma3, Laura Notarfranchi3, Sara Galimberti1, Gabriele Buda1. 1. Hematology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 2. General Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. 3. Hematology Unit and CTMO, Department of Medicine and Surgery, University of Parma, Parma, Italy. 4. Statistic analysis Unit, Department of Medicine and Oncology, Pisa University Hospital, Pisa, Italy.
Abstract
Background: Maintenance treatment after autologous bone marrow transplantation in multiple myeloma improves the outcome of patients. We designed a phase II clinical trial to evaluate the treatment with IL2 and zoledronate after autologous bone marrow transplantation in myeloma patients. Methods: Patients with a histologically proven diagnosis of multiple myeloma become eligible if achieved a very good partial remission in bone marrow samples after 3 months from autologous bone marrow transplantation. IL2 was administered from day 1 to 7. In the first cycle, the daily dose was 2 × 106 IU, whereas, in subsequent ones the IL2 dose was progressively escalated, with +25% increases at each cycle, until evidence of toxicity or up to 8 × 106 IU. Four mg of zoledronic acid were infused on day 2. Flow cytometry analysis of γδ-lymphocytes was performed at days 1 and 8 of treatment cycles. Results: Forty-four patients have been enrolled between 2013 and 2016. The median time to progression was 22.5 months (95% CI 9.7-35.2). A complete remission with a negative immunofixation was obtained in 18% of patients and correlated with a significantly longer time to progression (p = 0.015). Treatment was well tolerated without G3 or 4 toxicities. After a week of treatment with IL2 and zoledronate, γδ lymphocytes, Vγ9δ2, CD57+, effector, late effector, and memory γδ increased but in subsequent cycles, there was a progressive reduction of this expansion. Conclusions: The maintenance treatment with IL2 and Zoledronate has a modest activity in myeloma patients after autologous bone marrow transplantation. EudraCT Number: 2013-001188-22.
Background: Maintenance treatment after autologous bone marrow transplantation in multiple myeloma improves the outcome of patients. We designed a phase II clinical trial to evaluate the treatment with IL2 and zoledronate after autologous bone marrow transplantation in myelomapatients. Methods:Patients with a histologically proven diagnosis of multiple myeloma become eligible if achieved a very good partial remission in bone marrow samples after 3 months from autologous bone marrow transplantation. IL2 was administered from day 1 to 7. In the first cycle, the daily dose was 2 × 106 IU, whereas, in subsequent ones the IL2 dose was progressively escalated, with +25% increases at each cycle, until evidence of toxicity or up to 8 × 106 IU. Four mg of zoledronic acid were infused on day 2. Flow cytometry analysis of γδ-lymphocytes was performed at days 1 and 8 of treatment cycles. Results: Forty-four patients have been enrolled between 2013 and 2016. The median time to progression was 22.5 months (95% CI 9.7-35.2). A complete remission with a negative immunofixation was obtained in 18% of patients and correlated with a significantly longer time to progression (p = 0.015). Treatment was well tolerated without G3 or 4 toxicities. After a week of treatment with IL2 and zoledronate, γδ lymphocytes, Vγ9δ2, CD57+, effector, late effector, and memory γδ increased but in subsequent cycles, there was a progressive reduction of this expansion. Conclusions: The maintenance treatment with IL2 and Zoledronate has a modest activity in myelomapatients after autologous bone marrow transplantation. EudraCT Number: 2013-001188-22.
Authors: Gareth J Morgan; Walter M Gregory; Faith E Davies; Sue E Bell; Alexander J Szubert; Julia M Brown; Nuria N Coy; Gordon Cook; Nigel H Russell; Claudius Rudin; Huw Roddie; Mark T Drayson; Roger G Owen; Fiona M Ross; Graham H Jackson; J Anthony Child Journal: Blood Date: 2011-10-20 Impact factor: 22.113
Authors: Philip L McCarthy; Kouros Owzar; Craig C Hofmeister; David D Hurd; Hani Hassoun; Paul G Richardson; Sergio Giralt; Edward A Stadtmauer; Daniel J Weisdorf; Ravi Vij; Jan S Moreb; Natalie Scott Callander; Koen Van Besien; Teresa Gentile; Luis Isola; Richard T Maziarz; Don A Gabriel; Asad Bashey; Heather Landau; Thomas Martin; Muzaffar H Qazilbash; Denise Levitan; Brian McClune; Robert Schlossman; Vera Hars; John Postiglione; Chen Jiang; Elizabeth Bennett; Susan Barry; Linda Bressler; Michael Kelly; Michele Seiler; Cara Rosenbaum; Parameswaran Hari; Marcelo C Pasquini; Mary M Horowitz; Thomas C Shea; Steven M Devine; Kenneth C Anderson; Charles Linker Journal: N Engl J Med Date: 2012-05-10 Impact factor: 91.245