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1352 Immune Profiling Evaluation of Newly Diagnose Multiple Myeloma (NDMM) Transplant Eligible (TE) Patients Treated with Daratumumab, Cyclophosphamide, Thalidomide and Dexamethasone. Preliminary Results

Program: Oral and Poster Abstracts
Session: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster I
Hematology Disease Topics & Pathways:
multiple myeloma, Biological, antibodies, therapy sequence, Diseases, Combinations, Therapies, Biological Processes, immune cells, Cell Lineage, Plasma Cell Disorders, Lymphoid Malignancies, immune mechanism, microenvironment
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Allan de souza Santos, BS1*, Herbert Henrique de Melo Santos, MD2*, Marco Aurelio Salvino, MD, PhD3,4, Sarah Queiroz Silva, MD5*, Larissa Ferreira Lucas, MD6*, Alessandro de M. Almeida, MD7,8, Mariane Melo Santos, BS, MsC9*, Juliana Andrade Santos, MD10*, Vania T. M. Hungria, MD, PhD11, Maria da Gloria B. Arruda, MD, PhD12,13*, Alex Torres, PhD14* and Edvan De Queiroz Crusoe, MD, PhD15,16

1Immunology, mollecular and cytometry Laboratory- ICS, Federal University of Bahia, Salvador, Brazil
2Immunology, molecullar and Cytometry Laboratory- ICS, Federal University of Bahia, Salvador, Brazil
3Hematology and Bone Marrow Transplantation UNIT, Rede D'or Oncologia, Salvador, Brazil
4Universidade Federal De Bahia, Salvador, Brazil
5Hematology, Rede D'or Oncologia- Salvador, Salvador, Brazil
6Hematology, CLinica CEHON Rede D'or Oncologia, salvador, Brazil
7Stem Cell Transplant Unit, Federal University of Bahia, Salvador, Brazil
8Hematology and Bone Marrow Unit, Rede D´or Oncologia, salvador, Brazil
9Immunology, mollecullar and cytometry Laboratory- ICS, Federal University of Bahia, salvador, Brazil
10Hematology, Clinica CEHON Rede D'or oncologia, Salvador, Brazil
11Department of Hematology, Clinica São Germano and Santa Casa Medical School, São Paulo, Brazil
12Federal University of Bahia, Salvador, Brazil
13Hematology, Clinica CEHON Rede D'or Oncologia, salvador, Brazil
14Immunology, Federal University of Bahia, salvador, Brazil
15Rua Dra Doutro Vianna S/n, Universidade Federal da Bahia- Hospital Universitario, Salvador, Brazil
16Hematology department- D'or Oncologia, Clinica CEHON Rede D'or Oncologia, Salvador, Brazil

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<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.

*signifies non-member of ASH