Immune Profiling Evaluation of Newly Diagnose Multiple Myeloma (NDMM) Transplant Eligible (TE) Patients Treated with Daratumumab, Cyclophosphamide, Thalidomide and Dexamethasone. Preliminary Results
Authors: Santos Allan de souza , Santos Herbert Henrique de Melo , Salvino Marco Aurelio , Silva Sarah Queiroz , Lucas Larissa Ferreira , Almeida Alessandro de M. , Santos Mariane Melo , Santos Juliana Andrade , Hungria Vania T. M. , Arruda Maria da Gloria B. , Torres Alex , De Queiroz Crusoe Edvan 
Published: November 2020

Background: CD38-targeting antibody Daratumumab (Dara) has been demonstrating significant improvement in (MM) patient's survival. Cyclophosphamide (C), thalidomide (T) and dexamethasone (D) - (CTd) is one of the most used induction protocols worldwide and the MAX-Dara study was the first that combine Dara-CTd as induction for (NDMM) (TE) patients. We hypothesized that this new combo + autologous stem cell transplantation (ASCT) could affect the quantitative recovery of distinct lymphocytes subsets. Objective: Primary endpoint was to quantify lymphocytes subpopulations in (NDMM) (TE) patients at different treatment phases. Secondary endpoint was to evaluate B cells subsets at same times. Methods: Peripheral blood of 10 NDMM TE patients was collected at three different moments: at diagnose, after 4 induction cycles and after two consolidation cycles post- (ASCT). Dara-CTd protocol was for up to four 28-day induction cycles: C-500mg per oral (PO) d 1,8 and 15, T at 100-200mg PO d 1 to 28, Dex at 40mg PO d 1,8,15 and 22 and Dara 16mg/Kg/dose IV on d 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. Consolidation was started at D+30 after ASCT and all patients received up to four 28-day consolidation cycles: Dara 16mg/Kg and (D) at 40mg every other week, associated with T at 100mg PO d 1 - 28. Dara 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. Flow cytometry was used to detect lymphocyte surface by CD3, CD4, CD5, CD8, CD16, CD19, CD20, CD38, CD45 and CD56 in the scatter plot. B cells were isolated and subpopulations (naïve B cells, class and non-class switched memory B cells, , IgD-CD27- memory B cells and plasma blasts) were detected by CD20, CD24, CD27, CD38, CD45 and IgD. Statistical analysis was performed using the SPSS® v25.0. Results: The median number of lymphocytes subsets at diagnosis were 1139 x 10³/μL for T cells, 155 x 10³/μL for B cells and 284 x 10³/μL for NK cells. After four cycles of Dara-CTD the median number of T, B and NK cells had dropped to 834, 7.5 and 8.0 x 10³/μL respectively (p&lt;0.05). After two consolidation cycles post-ASCT, the T cells showed full reconstitution (1246 x 10³/μL) while B cells and NK cells had weakly reconstitution (20 x 10³/μL and 33 x 10³/μL, respectively). Regarding B cells subpopulations, the median B cell naïve numbers decreased from 32 x 10³/μL to 1 x 10³/μL (after 4 cycles), and recovery post-ASCT to 14 x 10³/μL. Class and non-class switched memory B cells numbers decreased after induction from 30 to 3.5 x 10³/μL and 37 to 2.0 x 10³/μL respectively. These subpopulations recovery after ASCT+ two consolidation cycles were not observed. Discussion: Different cells populations expresses CD38 antigen in their surface and depending on that, transitional lymphocytes counts reduction have been shown with different protocols using Dara. The present study confirmed that there is a decrease on total lymphocytes numbers after Dara- use. After two consolidation cycles post-ASCT, T cells counts had been recovered, while NK and B cells had a slightly recovery suggesting that Dara-CTD combination had a slighted negative impact in those lymphocytes' reconstitution. Concerning specifically B cells populations, we found that naive B cell was the first to showed faster recovery, although it was still below the reference range (33 - 259 x 10³/μL). Conclusion: This is the first study that reported lymphocyte profile with Dara plus CTD protocol. The preliminary data suggests that Dara-CTD reduces all lymphocytes populations after induction phase, but after ASCT followed by two consolidations cycles full reconstitution of T cells and slight recovery of B and NK cells was observed.

Disclosures

De Queiroz Crusoe: Janssen: Research Funding.