Daratumumab-containing Induction Effects on Stem Cells Mobilization, colLection and Engraftment in Newly Diagnosed Multiple MyelomA Patients.

Study Overview
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Brief Summary
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Daratumumab is a human first-in-class monoclonal antibody that targets a cluster of differentiation (CD) 38, a cell surface protein that is overexpressed on multiple myeloma (MM) cells, showing significant activity in relapsed/refractory disease. More recently, it was demonstrated that the addition of daratumumab to pre-autologous hematopoietic stem cell transplant (ASCT) induction regimens in newly diagnosed multiple myeloma increased the rate of complete responses and disease-free survival. However, in consideration of the expression of CD38 antigen also by stem cells, daratumumab could exert effects on their mobilization, collection, and engraftment. The primary objective of this retrospective/prospective observational study is to investigate the impact of adding daratumumab to standard induction regimens (VTD:bortezomib-thalidomide and dexamethasone, VD: bortezomib and dexamethasone) on stem cell mobilization in patients with newly diagnosed multiple myeloma (NDMM) who are candidates for ASCT.

Official Title
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Daratumumab-containing Induction Effects on Stem Cells Mobilization, colLection and Engraftment in Newly Diagnosed Multiple MyelomA Patients (DILEMMA).

Conditions
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Multiple Myeloma, Daratumumab, Autologous Stem Cell Transplantation, Leukapheresis

Intervention / Treatment
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* Drug: Daratumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. NDMM candidate to stem cell mobilization, collection, and ASCT who received a Daratumumab-containing induction regimen. Signed written informed consent to study participation. Exclusion Criteria: Age <18 y.o. Inability to obtain written informed consent. Patients not proceeding to stem cell mobilization because of disease progression. Patients not eligible for high-dose cyclophosphamide according to baseline cardiologic evaluation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases (prospective cohort)<br>Patients who fulfill the inclusion criteria (newly diagnosed multiple myeloma patients undergoing daratumumab-containing induction regimens). | Drug: Daratumumab<br>* NDMM (newly diagnosed multiple myeloma) who fulfill the inclusion criteria, candidate to stem cell mobilization, collection, and autologous stem cell transplant who receive a Daratumumab-containing induction regimen.<br>* Other names: Darzalex;|
| Controls<br>Patients with newly diagnosed multiple myeloma who received standard VTD (VTD:bortezomib-thalidomide and dexamethasone) induction, subsequent stem cell mobilization, and tandem autologous stem cell transplant before the introduction of daratumumab in our local practice from January 2020 to December 2021. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the difference in the mean number of collected CD34+ cells/kg during total harvest between Daratumumab and control group. | To assess the difference in the mean number of collected CD34+ cells/kg during total harvest between Daratumumab and control group. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion (%) of patients achieving at least two minimum transplant doses (4x10^6 CD34+ cells/kg) at first day of apheresis in Daratumumab versus control group. | Proportion (%) of patients achieving at least two minimum transplant doses (4x10^6 CD34+ cells/kg) at first day of apheresis in Daratumumab versus control group. | 12 months | 
| Proportion (%) of patients who received plerixafor rescue for poor mobilization in Daratumumab versus control group. | Proportion (%) of patients who received plerixafor rescue for poor mobilization in Daratumumab versus control group. | 12 months | 
| Graft composition in Daratumumab group in term of concentration of CD34+ cells x10^6/kg, TNC (total nucleated cells) x 10^8/kg, and MNC (mononuclear cells) x 10^8/kg. | Graft composition in Daratumumab group in term of concentration of CD34+ cells x10^6/kg, TNC (total nucleated cells) x 10^8/kg, and MNC (mononuclear cells) x 10^8/kg. | 12 months | 
| Rate (%) of CD38 expression and clonogenic potential of collected CD34+ cells in both groups. | Rate (%) of CD38 expression and clonogenic potential of collected CD34+ cells in both groups. | 12 months | 
| To compare transplant outcome in term of time (days) to platelets and neutrophils engraftment in Daratumumab versus control group. | To compare transplant outcome in term of time (days) to platelets and neutrophils engraftment in Daratumumab versus control group. | 12 months |