Thalidomide Does Not Compromise Mobilization with Cytokine Alone in Multiple Myeloma after Triplet Induction Regimen
Authors: Skerget Matevz , Sever Matjaz , Skopec Barbara 
Published: October 2019

Abstract
Background
Multiple myeloma (MM) is a hematologic disease characterized by accumulation of malignant plasma cells in the bone marrow. Triplet induction regimens incorporating bortezomib, thalidomid and dexamethasone (VTD) or bortezomib, cyclophosphamide and dexamethasone (VCD) are current standard of care because of improved response and prolonged progression free survival (PFS) and overall survival (OS). Autologous hematopoietic stem cell transplantation (aHSCT), performed in first remission or at relapse, is standard of care for younger fit patients. Successful mobilization and collection of peripheral blood stem cells (PBSC) is required before aHSCT. A target dose of 2 x 106 PBSC per kg body weight is considered a minimum for timely hematopoetic reconstitution, although a higher dose, 3 to 5 x 106 PBSC per kg body weight, is thought to be optimal for earlier engraftment. Mobilization with chemotherapy (intermediate doses of cyclophosphamide) and granulocyte-colony stimulating factor (G-CSF) is a standard in most transplant centers and provides higher stem cell yields in fewer apheresis procedures, at the cost of increased toxicity and less predictable onset date of apheresis in comparison to G-CSF alone mobilization. G-CSF alone mobilization fails to achieve the target doses of PBSC in up to 20 % of patients. There is limited information on possible impact of novel agents on ability to successfully mobilize and harvest PBSC. From available data, the impact of thalidomide on stem cell mobilization is small and probably not of clinical significance, but most of it comes from trials incorporating mobilization with chemotherapy and not G-CSF alone mobilization. Due to feasibility and safety reasons our institution uses G-CSF alone mobilization in MM patients. Mobilization with chemotherapy and/or prelixafor is reserved for poor mobilizers. The aim of our study was to retrospectively evaluate the success of GCSF alone mobilization in patients who received either VTD or VCD induction and possible differences between two groups.
Patients and methods
We retrospectively analyzed data from our national registry from the 1/1/2014 until 12/31/2017. Seventy-two patients with newly diagnosed MM that received induction treatment with VTD or VCD and underwent stem cell mobilization with G-CSF alone were included. VTD treatment consisted of 3 week cycles of bortezomib 1.3 mg/m2 subcutaneous on days 1, 4, 8 and 11, thalidomide 100 mg daily and dexamethasone 40 mg on days 1 - 4 of the first cycle and once per week thereafter. VCD treatment incorporated bortezomib and dexamethasone at the same schedule as for VTD plus cyclophosphamide 500 mg/m2 on day 1, 8 and 15 of each cycle. Following 3 - 4 cycles of induction treatment, stem cells were mobilized using daily subcutaneous injections of G-CSF 10 mg/kg body weight (doses were rounded up according to available 300 mcg and 480 mcg vials) for 5 consecutive days. The number of circulating PBSC was determined in peripheral blood on day 5 by flow cytometry and apheresis was initiated at a CD34+ cell count > 20/μL. A dose of 2 × 106 PBSC per kg body weight and 3 × 106 PBSC per kg body weight were considered the minimal and optimal dose for a single transplant.
Results
Twenty-eight and 44 patients received induction treatment with VCD or VTD respectively (Table 1). The mobilization failure rate between the groups was 7 % and 9 % for VCD and VTD. There was no statistical difference in the number of apheresis procedures, collected PBSC and the ability to collect a minimal and optimal dose for 2 aHSCT between the two groups (Table 2).
Conclusions
Due to higher efficacy, VTD is preferred over VCD with no data available on the impact of these regimens on stem cell mobilization with G-CSF alone. The results of our retrospective study showed that thalidomide in the VTD regimen did not influence the number of collected PBSC or the number of apheresis procedures compared to VCD. The failure rate for both groups was low. There was no statistical difference in collecting the optimal dose for two aHSCT between the groups. In conclusion, induction with VTD can be safely used in centers using G-CSF alone mobilization without compromising the ability for stem cell harvest.

Disclosures
No relevant conflicts of interest to declare.