Stem Cell Mobilization with Ixazomib and G-CSF in Patients with Multiple Myeloma

Simple Summary High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is the standard consolidation strategy for patients with newly diagnosed multiple myeloma (MM), as well as for a subset of patients with relapsed/refractory disease. ASCT reduces the duration of myelosuppression induced by HDCT. Chemotherapy agents combined with granulocyte-colony stimulating factors (G-CSF), as well as plerixafor, are key components of currently used stem cell mobilization regimens. However, chemotherapy mobilizing agents are associated with risk of infectious complications and peripheral neuropathy, which is as well a common toxicity of many drugs used in MM treatment. Ixazomib is an oral proteasome inhibitor and has lower neurotoxic potential. We for the first time combined ixazomib with G-CSF (filgrastim) for stem cell mobilization in patients with MM undergoing HDCT and ASCT, and assessed safety and efficacy of this mobilization strategy. Ixazomib was globally well tolerated and no new toxicities have been observed. The combination of ixazomib and G-CSF showed promising stem cell mobilizing activity and led to successful stem cell mobilization in 17 out of 19 (89%) patients. However, 9 (47%) patients required the addition of plerixafor to ensure optimal stem cell collection. Future larger studies might further investigate the role of ixazomib in stem cell mobilization regimens for MM. (1) Background: High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is the standard consolidation strategy for patients with newly diagnosed multiple myeloma (MM) and for a subset of patients with relapsed/refractory disease. For stem cell mobilization, G-CSF alone or in combination with chemotherapy mobilizing agents and/or plerixafor are commonly used. Ixazomib is an oral proteasome inhibitor with less neurotoxic potential, which previously showed the ability to mobilize stem cells in preclinical studies. (2) Methods: Prospective single-center phase 1 study assessing the efficacy and safety of stem cell mobilization with ixazomib and G-CSF in patients with newly diagnosed or relapsed/refractory MM undergoing HDCT and ASCT. Primary endpoint was percentage of patients achieving a yield of at least 6.0 x 10(6)/kg CD34+ cells within the first apheresis. G-CSF (filgrastim) 10 mu g/kg/day was administered subcutaneously (s.c.) from day 1 to day 5 (planned apheresis) and ixazomib 4 mg orally at day 4. Plerixafor 24 mg s.c. was administered if the stem cell mobilization with ixazomib and G-CSF was not sufficient. (3) Results: 19 patients were treated within the study between 06/2020 and 02/2021. The primary endpoint was reached in 17 (89%) patients, with a median of 7.1 x 10(6)/kg CD34+ cells collected within the first apheresis, comparable to previously published results, and only 2 (11%) patients required a second apheresis. Median number of circulating CD34+ cells was 14.0 x 10(6)/L (2.0-95.2) before the administration of ixazomib, and 33.0 x 10(6)/L (4.2-177.0) pre-apheresis. However, 9 (47%) patients required the addition of plerixafor to ensure optimal stem cell collection. (4) Conclusions: The combination of ixazomib and G-CSF showed promising stem cell mobilizing activity in patients with MM prior to HDCT and ASCT. Future larger studies might further investigate the role of ixazomib in stem cell mobilization regimens for MM.