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Background: Newly drugs access for MM treatment still a challenge in some countries. One of the most available inductions for TE NDMM patients (pts) worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)-(CTd). Dara the first anti- CD38, had been combined with VCd, VTd and VRd and markedly increased the depth and duration of the response. We hypothesized that Dara and CTd combination could be safe and allow deeper activity as an alternative protocol. Aims: The aims of this analysis were to evaluate Progression Free Survival (PFS) of Dara-CTd treatment and minimal residual disease (MRD) after one year of Dara maintenance. Primary endpoint of the study was to evaluate the VGPR after two consolidation cycles post-autologous stem cell transplantation (ASCT). Methods: This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TE NDMM, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the Easter Cooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, (d) at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. All pts received up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. G-CSF was used for stem cell (SC) mobilization and plerixafor had been allowed whenever the pts need. The MRD was evaluated by next-generation flow (NGF) based and PET-CT was performed when the patient obtained NGF negativity or finished consolidation. PFS outcome was estimated using Kaplan-Meier method. All pts received antiviral, anti-pneumocystis and anti-thrombotic prophylaxis. Data cut-off was June 15, 2021. Results: The first pts was enrolled in November 2018. A total of 24 pts were included, the median age being 60 (range 37- 67 years), 23 (92%) were non-white, 5 (21%) had an R-ISS = 1, 12 (54%) had an R-ISS = 2 and 4 (16%), an R-ISS = 3. Six (25%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, all pts have completed induction, 20 have received transplant and 17 have completed D+90 post-transplant assessment. No SC mobilization failure was observed, and six (30%) pts needed plerixafor use. By ITT analysis after a median follow up of 20 months the PFS at 12 and 18 months was 86%. No PFS difference was observed between different subgroups. Regarding response rates, after the end of induction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity by NGF. 17 pts have completed two consolidation cycles after transplant and 94% obtained > VGPR as best response, 13 (76%) obtained MRD negativity by NGF and 10 (58%) had negative PET-CT. Seven (41%) pts had both flow and PET-CT negativity. Six pts completed one year of maintenance and five of them (83%) still MRD negativity by NGF. Four pts died from infection, two of them related with covid infection (one before transplant and one during maintenance). Another case post-transplant, considered not related to the investigational agent and one after consolidation, related to the investigational agent. Two pts have discontinued treatment due to progression - 1 before ASCT e 1 during maintenance. The most common adverse events (AEs) grades 3 and 4 were neutropenia (n = 12), infusion reaction (n = 7), neuropathy (n = 6), lymphopenia (n = 4), infection (n = 3), hypertension (n = 1) and rash (n = 1). Summary/Conclusion: The Daratumumab - CTd protocol is an active regimen capable of producing deep and sustainable responses and improve the PFS of NDMM TE pts with a favorable safety profile. Clinical trial information: NCT03792620. Disclosures De Queiroz Crusoe: Janssen: Research Funding. Hungria: Sanofi: Honoraria, Other: Support for attending meetings/travel ; Takeda: Honoraria; Abbvie: Honoraria; Amgen, BMS, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings/travel .

Introduction- Next generation flow (NGF) is one of the approaches for testing multiple myeloma (MM) minimal residual disease (MRD) over conventional response assessments. Actually, bone marrow (BM) is the preference site of evaluation because of its sensitivity. Because of its invasively technic, other possible sites for MRD evaluation outside the BM have been studied. In the present study we analyzed the MRD between the BM and the hematopoietic stem cell collected product (HSC product), once the concentration of plasma cell in the HSC product could be higher than peripheric blood sample. Aims- To compare MRD quantification of plasma cell between BM and HSC product after induction from Newly Diagnosed MM(NDMM) Transplant Eligible (TE) patients (pts) exposed to daratumumab, cyclophosphamide, thalidomide and dexamethasone (Dara-CTD) protocol. Methods- The SC product and BM samples were collected after four 28 days cycles of induction therapy from pts treated with Dara-CTd protocol described before by (Crusoe E. et al. Blood 2020; 136 (supplement 1): 17-18). MRD was evaluated by next-generation flow (NGF) based in the EuroFlow® protocol. EuroFlow standards was used to identify clonality and aberrant PC immune phenotype, consisting by EuroFlow 8-color 2-tube method (MM MRD kit, Cytognos, Salamanca), with the acquisition of 5 million events each tube and then merged into a single analysis tube on approximately 10 million events. Plasma cells were identified by CD38 multiepitope and CD138. Other markers were used to detect abnormal phenotypes. For comparison of MRD results, Bland-Altman plot comparing BM-MRD and HSC product-MRD was performed. Results- The first pts was enrolled in November 2018. A total of 24 pts were included, the median age was 60 (range 37- 67 years), 23 (92%) were non-white, 5 (21%) had an R-ISS = 1, 12 (54%) had an R-ISS = 2 and 4 (16%), an R-ISS = 3. Six (25%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, all pts have completed induction and 20 have received transplant. Regarding response rates, after the end of induction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity by NGF. 19 pts were analyzed for MRD. Negative MRD in sensitivity =10 -5 and =10 -4 evaluated in bone marrow was 4/19(21%), 4/19(21%), 11/19(58%) respectively. Negative MRD in sensitivity =10 -5 and =10 -4 evaluated in the HSC product was 13/19(68%), 3/19(16%), 3/19(16%) respectively. Median bone marrow sensitivity 10 -4 lower quartile 10 -5 upper quartile 10 -3. Normal distribution of the differences between BM and SC product MRD was first assessed (Kolmogorov-Smirnov's p < 0.001, n = 19). Discussion-Conclusions- The use of HSC product could enhance the plasma cell concentration and may be an alternative and attractive method for MRD detection that diminished the invasiveness of repetitive bone marrow aspirations and tackling the heterogeneity distribution of MM cells. In this preliminary data the sample size did not allow to show a direct correlation between BM and HCS product. A larger sample would be needed to confirm the hypothesis. Figure 1 Figure 1. Disclosures Hungria: Amgen, BMS, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings/travel ; Abbvie: Honoraria; Sanofi: Honoraria, Other: Support for attending meetings/travel ; Takeda: Honoraria. De Queiroz Crusoe: Janssen: Research Funding.

Background: The inclusion of the CD38-targeting antibody daratumumab (Dara) increases the depth and duration of the response, as demonstrated by Dara-VTd and Dara-VRd protocols to treat NDMM - TE patients (pts). However, the access to new drugs is a challenge for some countries in Latin America. There are many induction protocols and one of the most used inductions worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)- (CTd). We hypothesized that the combination of daratumumab and CTd (Dara-CTd) could be safe and allow deeper activity in NDMM TE pts. Objective: The primary endpoint was the attainment of VGPR after two consolidation cycles post-autologous stem cell transplantation (ASCT). Secondary endpoints were the overall response rate during all treatment phases and minimal residual disease (MRD), based on the International Myeloma Working Group (IMWG) criteria that includes the next-generation flow by the EuroFlow® and PET-CT and the safety profile. An exploratory endpoint was the analysis of the immunologic change in the lymphocyte profile during the treatment. Methods: This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: NDMM TE, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the Easter Cooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol scheme was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, Dex at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 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 transplant and all patients received up to four 28-day consolidation cycles: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. All patients received antiviral, anti-pneumocystis and anti-thrombotic prophylaxis. Results: The first patient was enrolled in November 2018. A total of 21 pts were included, the median age being 56 (range 38 - 67 years), 18 (85%) were non-white, 3 (14%) had an R-ISS = 1, 12 (57%) had an R-ISS = 2 and 3 (14%), an R-ISS = 3. Five (24%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, 18 pts have completed induction, 12 have received transplants and 10 have completed D+90 post-transplant assessment. In an intention to treatment analysis, after the end of induction (cycle 4), 17 (95%) of the pts obtained > PR and 7 (33%) obtained VGPR or better. Ten patients have completed two consolidation cycles after transplant and 100% obtained > VGPR as best response, 8 (80%) obtained MRD = -10-5 negative remission by flow cytometry and 6 (60%) had negative PET-CTs. Five (50%) patients had both flow and PET-CT negativity. Two patients died from infection, one post-transplant, considered not related to the investigational agent, and another after consolidation, related to the investigational agent. The most common non-hematological adverse events (AEs) grades 3 and 4 before ASCT were neuropathy (n = 6), infusion reaction (n = 6), infection (n = 2), hypertension (n = 1) and rash (n = 1). Conclusion: This is the first study that combined daratumumab with CTd as induction for NDMM TE patients. This preliminary data has shown that the association of Dara-CTd achieved a deep response with a safety profile. Clinical trial information: NCT03792620. Disclosures De Queiroz Crusoe: Janssen: Research Funding.

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 Disclosures De Queiroz Crusoe: Janssen: Research Funding.