Session: 652. Multiple Myeloma: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Research, Plasma Cell Disorders, Diseases, Lymphoid Malignancies
The high sensitivity of M-InSight enables the quantification of M-protein at much lower concentrations than current blood techniques used for diagnostic, which makes it possible to track low level M-protein and potentially detect a relapse before the apparition of new symptoms.
The main objective of this study was to show that M-insight can monitor MRD in blood samples of MM patients treated by isatuximab during the maintenance phase.
Samples from 15 newly diagnosed non eligible for transplantation MM patients from a Sanofi clinical trial (NCT02513186) were chosen to monitor MRD by M-InSight. All patients were selected from the VRDI Part B (bortezomib, lenalidomide, dexamethasone) consisting of evaluating the preliminary efficacy (complete response [CR] rate) of isatuximab administered at the selected dose in combination with bortezomib based regimen. The treatment period included 4 induction cycles (24-week duration), followed by a maintenance period consisting of 4 weeks cycles until progression, unacceptable AE, or patient willingness to discontinue. M-InSight was used to sequence the M-protein (collected predose at Day 1 of Cycle 1) and to measure M-protein concentration in the serum samples collected during the maintenance phase. Results were compared to SPEP, IFE and MRD at 10-6 sensitivity by clonoSEQ®️ (Adaptive Biotechnologies).
After 4 cycles of induction, all patients had Very Good Partial Response. Rate of 9/15 CR, 5/15 VGPR and 1 sCR was observed as the best overall response. NGS MRD data were obtained for 14 patients of which 8 reached MRD negativity at 10-6 sensitivity. 4 of the remaining 6 patients relapsed during maintenance.
Clonotypic peptides were identified in all 15 patients from the baseline sample. A total of 302 serum samples collected during maintenance were analyzed. M-protein quantification was highly concordant with the one obtained by SPEP when available (Pearson R=0.78, p<0.01). 100% of patients that were MRD positive by NGS 10-6 were MS-MRD positive and could be quantified by M-InSight. 60% of patients that were MRD negative by NGS 10-6 were still positive and quantifiable by M-InSight, suggesting higher sensitivity. The remaining 40% was negative by both NGS and MS. M-insight was able to monitor the disease on 5 patients that had sustained MRD (consecutive MRD negativity) and stable M-protein levels (no increase or decrease of M-protein by 2-fold for 2 consecutive time points). All 4 patients that developed PD had an increase of M-protein of at least 2-fold in 2 consecutive time points showing that M-InSight was able to provide an earlier detection of relapse, when SPEP was still negative for 3 of these. Only one patient had unmeasurable M-protein concentration, staying unmeasurable for 1 year and negative by NGS MRD. The lowest M-protein concentration measured by M-InSight was 0.01 mg/dL (10 mg/dL).
This study shows that MRD monitoring on blood is feasible using an ultra-sensitive technique, avoiding invasive bone-marrow aspiration. M-InSight shows accurate monitoring of the depth and kinetics of response to treatment thanks to frequent timepoints. M-InSight can track low level of M-protein in CR patients and detect early relapse.
Disclosures: Di Stefano: Sebia: Current Employment. Mouktadi: Sebia: Current Employment. Bonifay: Sebia: Current Employment. Rougé Dubroc: Sebia: Current Employment. Sonigo: Sebia: Current Employment.
OffLabel Disclosure: Isatuximab is not approved in front line.
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