Phase II Trial of Maintenance Treatment With IL2 and Zoledronate in Multiple Myeloma After Bone Marrow Transplantation: Biological and Clinical Results

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 x 10(6) 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 x 10(6) IU. Four mg of zoledronic acid were infused on day 2. Flow cytometry analysis of gamma delta-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, gamma delta lymphocytes, V gamma 9 delta 2, CD57+, effector, late effector, and memory gamma delta 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.