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Background: CT053 is a fully human autologous chimeric antigen receptor (CAR) T-cell therapy comprising a B-cell maturation antigen (BCMA)-specific single-chain variable fragment (25C2). A clinical trial of CT053 is ongoing in LUMMICAR STUDY 1 (NCT03975907) for patients with relapsed and refractory multiple myeloma (RRMM) in China. The pivotal Phase 2 of LUMMICAR STUDY 1 is actively enrolling patients. Here, we report clinical data from Phase 1 with 12 months of follow-up. Methods: Subjects with RRMM who had received ≥3 prior therapies, including at least one proteasome inhibitor and one immunomodulatory drug were enrolled in Phase 1 study. Adverse events (AEs) were graded according to CTCAE, v5.0; Cytokine release syndrome (CRS) and neurotoxicity were graded according to ASTCT CRS consensus grading system (Lee DW et al, 2019). Response was assessed per IMWG 2016 criteria. Minimal residual disease (MRD) was tested by next-generation flow cytometry on bone marrow aspirates by the EuroFlow assay with a minimum sensitivity of 1 in 10⁵ nucleated cells or higher, and CAR copies in the subject peripheral blood were monitored by quantitative real-time polymerase chain reaction (qPCR). Results: Fourteen subjects with a median age of 54 years (range 34-62) received CT053 infusion. Three subjects received 1.0×10 8 CAR+ T cells and eleven subjects received 1.5×10 8 CAR+ T cells. As of July 8, 2021, 14 subjects with a median follow-up of 13.6 months since infusion. Of the 14 subjects, 11 (78.6%) had received autologous stem cell transplantation, 2 (14.2%) had extramedullary disease at baseline, 2 (14.3%) had ISS stage III, and 5 (35.7%) had high-risk cytogenetics. The median prior therapies was 6 (range 3-7) and no subject received bridging therapy. The most common AEs were expected hematological toxicities. All subjects (100%) experienced ≥ grade 3 neutropenia, 91.7% experienced ≥ grade 3 thrombocytopenia, and most recovered to ≤ grade 2 within 2 weeks. No dose limiting toxicity or treatment-related death was reported. Additionally, no ≥ grade 3 CRS or neurotoxicity was observed, 92.9% subjects (13/14) experienced grade 1 or 2 CRS (9 grade 1, 4 grade 2). CRS occurred at a median of 6 days (range 2-12) post-infusion with a median duration of 7 days. No severe infections were reported except one case of grade 3 lung infection. A 100% overall response rate was achieved in 14 subjects, with 11 stringent complete responses (sCR, 78.6%), 2 very good partial responses (VGPR), and 1 partial response, with a ≥VGPR rate of 92.9%. Four subjects achieved sCR at week 52. As of July 8, 2021, 12 subjects with at least 12 months of efficacy assessment were still in the study, and the 12-month progression-free survival (PFS) rate was 85.7%. With a median follow-up of 13.6 months, the median duration of response and the median PFS had not been reached. All 11 subjects with sCR were MRD-negative, and 9 subjects reached sustained CR/sCR for more than 12 months (Figure 1). Three subjects had disease progressed including two subjects with extramedullary disease progressed at week 16. Interestingly, the CR/sCR rate for the subjects without extramedullary disease is 91.7% (11/12). The 1-year PFS rate for subjects without extramedullary disease reached 100%。 CT053 cells expanded and persisted well. No immunogenicity was detected. Conclusion: These results demonstrate that CT053 CAR T cells at a dose of 1.0-1.5×10 8 cells achieve a deep and durable response, including a high MRD-negative sCR rate, with an acceptable safety profile in subjects with heavily pretreated RRMM. Figure 1 Figure 1. Disclosures Li: CARsgen: Current Employment, Current equity holder in publicly-traded company. Wang: CARsgen Therapeutics Corp: Current Employment. Xiao: CARsgen Therapeutics Corp: Current Employment. Wang: CARsgen Therapeutics Co. LtD: Current Employment, Current equity holder in publicly-traded company. Tang: CARsgen Therapeutics Corp: Current Employment.

Background Bortezomib with lenalidomide and dexamethasone (VRd) is a standard regimen for the induction treatment of multiple myeloma (MM) transplant eligible and ineligible patients. Deregulation of histone acetylation has been recognized to serve a critical role in the pathogenesis of MM, which histone deacetylase (HDACs) are overexpressed in plasma cells derived from patients with MM. Therefore, HDACs may promise targets for MM therapy, and panobinostat was approved by FDA for the treatment of relapsed/refractory MM in 2015. Chidamide, a novel oral benzamide type HDAC inhibitor independently developed and approved as anticancer drugs in China, selectively suppresses the activity of class I HDACs. Our studies have shown that chidamide can enhance cytotoxic effect of bortezomib or lenalidomide on MM cells in vitro, which suggested a synergistic combination of chidamide with bortezomib or lenalidomide at low dose. In ASH 2019 we reported Phase 1 Suzhou MM02 study in which chidamide at 4 dose levels (15mg/20mg/25mg/30mg d 0,3,7,10) were administered to 12 patients with VRd for 4-cycle induction therapy. No DLT in Chi-VRd group were observed. This phase 2 trial was designed to further assess the safety and efficacy of Chi-VRd versus VRd for induction treatment in patients with newly diagnosed high risk MM before autologous transplantation (NCT 04025450). Methods In this study, we enrolled patients from the First Affiliated Hospital of Soochow University and Soochow Hopes Hematology Hospital with newly diagnosed high-risk multiple myeloma who were aged 18 years or older and eligible for autologous stem-cell transplant (ASCT) according to International Myeloma Working Group diagnostic criteria. All the patients were randomly assigned to Chi-VRd and VRd group. Chi-VRd group patients received Chidamide 20mg orally on days -1,2,6 and 9 in combination with VRd (bortezomib 1.3mg/m2 subcutaneously on days 1,4,8,11; lenalidomide 25mg orally on days 1-14; dexamethasone 20mg iv or orally on days 1,2,4,5,8,9,11,12) for 4 cycles. VRd group patients received VRd (bortezomib 1.3mg/m2 subcutaneously on days 1,4,8,11; lenalidomide 25mg orally on days 1-14; dexamethasone 20mg iv or orally on days 1,2,4,5,8,9,11,12) for 4 cycles. All the patients proceed with ASCT after four cycles or continue VRd therapy for up to eight cycles, followed by maintenance therapy for up to 2 years. Primary efficacy endpoints were overall response rate (ORR), rate of very good partial response (VGPR) or better and rate of complete response (CR) for Chi-VRd and VRd. Safety data described rates of adverse events. Results Between Mar 16, 2020, and Jul 22, 2021, 40 patients were enrolled and randomly assigned to either the VRd regimen (n=20) or the Chi-VRd regimen (n=20). In the Chi-VRd group, 1 patient was discharged due to severe tumor lysis syndrome, and another 1 patient was discharged from sick sinus syndrome (considering lenalidomide related). By the deadline for submission, 18 patients in the VRd group and 11 patients in the Chi-VRd group had completed induction chemotherapy. The total adverse events were listed in the table below. The main treatment-related adverse events were hematological toxicity, hepatotoxicity, constipation, and peripheral neuropathy. ORR was 90.9% (10/11) for Chi-VRd and was 100% for VRd. Response of VGPR or better was 81.8% (9/11) for Chi-VRd and was 83.3% (15/18) for VRd. And rate of CR was 63.6%(7/11) for Chi-VRd and was 44.4%(8/18) for VRd. Conclusion The Chi-VRd group had more adverse events of thrombocytopenia, peripheral neuropathy and pulmonary. No treatment-related death was observed in two groups. Patients received Chi-VRd get more CR rate. Updated PFS and OS with comparison between VRd and Chi-VRd will be presented at the following study. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: CT053 are autologous T cells genetically modified with a second-generation chimeric antigen receptor (CAR) incorporating a fully human B-cell maturation antigen (BCMA)-specific single-chain fragment variant (25C2) with high binding affinity. Twenty-four subjects were previously treated in investigator-initiated (IIT) studies with 87.5% overall response rate (ORR), 79.2% complete response (CR) and a median duration of response of 21.8 months without inducing immunogenicity [Blood (2019) 134 (Supplement_1): 4435]. We report herein the first disclosed results from the ongoing phase 1 study (LUMMICAR-1) in China (NCT03975907). Methods: The phase 1 study included subjects with relapsed/refractory multiple myeloma (RRMM) who had received ≥3 prior therapy regimens including a proteasome inhibitor and an immunomodulatory drug, and had measurable disease per 2016 International Myeloma Working Group (IMWG) criteria. All subjects received conditioning treatment of cyclophosphamide (300 mg/m2/day ×3 days) and fludarabine (25 mg/m2/ day × 3 days). After conditioning, subjects received a single infusion of CT053 at the 1.0-1.5×108 CAR+ T-cell dose. Primary objectives for phase 1 were to evaluate the safety and tolerability of CT053 and to identify the recommended phase 2 dose. Adverse events (AEs) were graded using CTCAE, v5.0; cytokine release syndrome (CRS) and neurotoxicity were graded according to ASTCT CRS consensus grading system (Lee DW et al, 2019). Response was assessed per 2016 IMWG criteria. Results: As of July 20, 2020, a total of 14 subjects have been enrolled in the study. All 14 subjects have been apheresed and received CT053 infusion, including 3 subjects who received 1.0×108 CAR+ T cells and 3 subjects who received 1.5×108 CAR+ T cells at dose escalation, followed by 8 subjects who received 1.5×108 CAR+ T cells at dose expansion. The 14 batches of CT053 were manufactured in a median of 8 days (range 7-10). Treated subjects had a median age of 54 years (range 34-62) and had received a median of 6 (range 3-7) prior lines of therapy. Of the 14 subjects, 10 (71.4%) received autologous stem cell transplantation, 2 (14.2%) had extramedullary disease at baseline, and 5 (35.7%) had high-risk cytogenetics. No subject received bridging therapy. At data cutoff, 12 subjects had at least 4 weeks of safety and efficacy assessment with median follow-up of 5 months (range, 1-11). No dose-limiting toxicities were detected. The most common ≥ grade 3 AE was hematological toxicity. Of the 12 subjects with at least 4 weeks follow-up, all experienced ≥ grade 3 neutropenia (100%), 91.7% of subjects had ≥ grade 3 thrombocytopenia, and most recovered to ≤ grade 2 within 2 weeks. No grade 3 or higher CRS or neurotoxicity was observed. Eleven of 12 subjects (91.7%) experienced grade 1 or 2 CRS, including 3 subjects who experienced grade 2 CRS and 8 subjects who experienced grade 1 CRS. CRS events occurred at a median of 6 days (range 2-12) post-infusion with a median duration of 7 days, following a generally predicable onset pattern. Eight subjects received tocilizumab treatment, of whom one subject with grade 2 CRS received both tocilizumab and steroid. At the data cutoff, among 12 subjects with at least 4 weeks of efficacy assessment, a 100% ORR was observed, with 4 stringent complete responses (sCR), 1 CR, 3 very good partial responses and 4 partial responses. All 5 subjects with CR/sCR were minimal residual disease (MRD)-negative at the 10 5 sensitivity level. Responses were independent of baseline BCMA expression in bone marrow. CT053 transgene levels showed expansion and persistence in peripheral blood, with peak expansion at 7-14 days after dosing in all subjects, with peak copies 45,469 (range 11,825-258,574). Serum C-reactive protein and cytokine levels (i.e., IL-6, IFNγ, IL-8, IL-10) increased post-infusion within 7 days and correlated with the onset of CRS symptoms. No immunogenicity was detected. Conclusion: These results demonstrate that CT053 at a target dose of 1.0-1.5×108 CAR+ T cells delivers early and deep responses, including MRD negativity in all complete responders, with an acceptable safety profile in subjects with heavily pretreated RRMM. The results from this LUMMICAR-1 study are consistent with the previous IIT phase 1 studies and the ongoing North American LUMMICAR-2 study and support the launch of pivotal LUMMICAR-1 study in China. Updated results will be presented at this conference. Disclosures Li: CARsgen Therapeutics Co. LtD: Current Employment, Current equity holder in private company. Wang:CARsgen Therapeutics Corp.: Current Employment. Xiao:CARsgen Therapeutics Corp.: Current Employment. Wang:CARsgen Therapeutics Co. LtD: Current Employment, Current equity holder in private company. Ma:CARsgen Therapeutics Corp.: Current Employment.

CT053 comprises autologous T cells genetically modified with a second-generation chimeric antigen receptor (CAR) incorporating a fully human B-cell maturation antigen (BCMA)-specific single-chain fragment variant (25C2) with high binding affinity. Twenty-four subjects have been treated in phase 1 studies with an 87.5% overall response rate (ORR), 79.2% complete response (CR), and a median duration of response of 21.8 months without inducing immunogenicity [Blood (2019) 134 (Supplement_1): 4435]. Here we present the ongoing phase 1b/2 study (LUMMICAR-2) conducted in North America (NCT03915184) to evaluate safety and clinical efficacy. Eligible subjects with relapsed/refractory multiple myeloma (RRMM) had received ≥3 prior lines of therapy including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 antibody, and had measurable disease per International Myeloma Working Group (IMWG) criteria. All subjects received a lymphodepletion regimen of cyclophosphamide (500 mg/m2/day ×2 days) and fludarabine (25 mg/m2/ day × 3 days). A single infusion of CT053 at the targeted 1.5-3.0×108 CAR+ T-cell dose was administered after lymphodepletion. Primary objectives for phase 1b were to evaluate the safety and tolerability of CT053 and to identify the recommended phase 2 dose. Adverse events (AEs) were graded using CTCAE, v5.0; cytokine release syndrome (CRS) and neurotoxicity were graded according to ASTCT CRS consensus grading system (Lee DW et al, 2019). The response was assessed per 2016 IMWG criteria, and minimal residual disease (MRD) was assessed by next generation flow cytometry or sequencing. As of July 28, 2020, 20 subjects have enrolled, and 14 subjects have received CT053 infusion in the phase 1b portion of the study, including 8 subjects who received 1.5-1.8×108 CAR+ T cells while 6 subjects received 2.5-3.0×108 CAR+ T cells. The treated subjects had a median age of 59 years (range 42-73), had received a median of 6 (range 3-11) prior lines of treatment, 93% were triple refractory to a PI, IMiD, and anti-CD38 antibody, and 64% were penta-refractory. In addition, 36% of the subjects had extramedullary disease at baseline, and 64% had high-risk cytogenetics. All subjects received bridging therapy. The most common ≥ grade 3 AE was hematological toxicity. All subjects experienced ≥ grade 3 neutropenia (100%) and leukopenia (100%), and 36% of subjects had ≥ grade 3 thrombocytopenia within 30 days of treatment. No grade 3 or higher CRS or neurotoxicity was observed. Twelve of 14 subjects (86%) experienced grade 1 or 2 CRS, including 2 subjects who experienced grade 2 CRS and 1 subject who had grade 2 neurotoxicity. CRS events had a generally predictable time to onset, occurring at a median of 2 days post infusion with a median duration of 4 days (range 1-6). Two subjects received tocilizumab, and one subject with grade 2 CRS received both tocilizumab and steroids. One subject experienced grade 2 neurotoxicity with complete resolution within 24 hours upon administration of dexamethasone. At the data cutoff, 10 subjects were evaluable for at least two months of efficacy assessment with a median follow-up of 4.5 months (range 2-8). A 100% ORR was observed, with 2 stringent complete responses, 2 CRs, 1 very good partial response, and 5 partial responses. Of the 12 subjects with evaluable bone marrow samples, 11 were MRD-negative at the 10-5 sensitivity level. Responses were independent of baseline bone marrow BCMA expression. CT053 transgene levels showed expansion and persistence in peripheral blood, with peak expansion at 7-14 days after infusion. All subjects showed similar kinetics of rapid declines in serum free light chains and soluble BCMA (sBCMA) levels within 1 month, and continued depletion in sBCMA suggests CT053-mediated pharmacodynamic activity. Serum C-reactive protein and cytokine levels (i.e., IL-6, IFNγ, IL-8, IL-10) increased post-infusion within 7 days and correlated with the onset of CRS symptoms. Collectively, these results demonstrate that CT053 at a target dose of 1.5-3.0×108 CAR+ T cells delivers early and deep responses, including MRD negativity, with an acceptable safety profile in subjects with heavily pretreated relapsed or refractory MM. The promising results from the ongoing LUMMICAR-2 study are consistent with the previous phase 1 studies and support the launch of a pivotal Phase 2 LUMMICAR-2 study. Updated results will be presented at the conference. Disclosures Kumar: Carsgen: Other, Research Funding; Kite Pharma: Consultancy, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Adaptive Biotechnologies: Consultancy; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Dr. Reddy's Laboratories: Honoraria; Tenebio: Other, Research Funding; Genecentrix: Consultancy; BMS: Consultancy, Research Funding; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; MedImmune: Research Funding; Cellectar: Other; Merck: Consultancy, Research Funding; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; Novartis: Research Funding; Karyopharm: Consultancy. Baz:Sanofi, Karypharm, Janssen, Celgene: Other: Advisory board; Karyopharm, janssen, Bristol Myers Squibb, Celgene, Merck, Sanofi, Abbvie Inc.: Research Funding. Orlowski:Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; STATinMED Research: Consultancy; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding. Anderson:Amgen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Ma:CARsgen Therapeutics Corp.: Current Employment. Bilgi:CARsgen Therapeutics Corp.: Other: Current shareholder in the company. Kansagra:Alnylam Pharmaceuticals, Bristol Myers Squibb /Celgene, GlaxoSmithKline, Janssen, Pharmacyclics, Takeda Pharmaceuticals, Pfizer, Karyopharm Therpeutics: Other: Advisory Board. Kapoor:Janssen: Research Funding; Cellectar: Consultancy; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Celgene: Honoraria; Amgen: Research Funding; Sanofi: Consultancy, Research Funding. Li:CARsgen Therapeutics Co. LtD: Current Employment, Current equity holder in private company. Brayer:Bristol-Myers Squibb, WindMIL Therapeutics: Research Funding; Janssen: Consultancy; Bristol-Myers Squibb, Janssen, Amgen: Speakers Bureau.

Background Multiple myeloma (MM) is a heterogenous plasma cell malignancy. About 30-40% of newly diagnosed and 20-60% of relapsed/refractory MM patients carry 1q21 amplification worldwide, a high-risk indicator for poor prognosis in RRMM. Different BCL-2 family anti-death proteins play important roles in MM survival and drug resistance. High expression of BCL-2 due to t (11;14) renders cell vulnerability to BCL-2 antagonist, however, patients carrying other genetic abnormality including 1q21 amplification have limited response to the newly emerged treatment choice. With MCL-1 upregulation accompanied with 1q21 amplification, we tested whether BCL-2 antagonist combined with IMiDs (immunomodulatory imide drugs), improves cell killing in high-risk MM patient models, including those resistant to bortezomib and lenalidomide. For that aim, we studied APG-2575, a novel and potent BCL-2 inhibitor developed by Ascentage Pharma Group and it is currently in clinical trials for hematologic malignances, including MM. Methods 1. Cells were treated with APG-2575 single agent or in combination with lenalidomide; 2. Cell line viability was assessed by CellTiter-Glo (CTG) assay; 3. Flow cytometry analysis was used to detect CD138+ cell surface marker in primary cells derived from MM patients; 4. Western blot analysis for BCL-2 family and IMiD signaling proteins. Results We first determined the cell sensitivity of APG-2575 as a single agent in a panel of MM cell lines, and as expected, those carrying t (11;14) were very sensitive to APG-2575, with low IC50 values ranging 7-23 nM. The IC50 values for cells carrying other genetic markers were greater than 5-10 μM. We then evaluated cell-death inducing activity of APG-2575 in MM patient-derived primary cells ex vivo, which were freshly prepared from patients' bone marrow aspirates. Primary cells were treated with APG-2575 or ABT-199 (venetoclax) for 18-24 hours, and the loss of CD138 surface marker was used to quantify cell death. As shown in Figure 1a, APG-2575 induced cell death (CD138+ loss) in a dose-dependent manner, and significant cell death was observed at 0.37-3.3 μM of APG-2575, indicating primary cells more sensitive than MM cell lines. Interestingly, the sensitivity to APG-2575 is similar in primary MM cells with or without 1q21 amplification. Since moderate cell death inducing activity was observed in MM cells when APG-2575 used as a single agent, we combined APG-2575 with lenalidomide. Cell death was increased in the combination groups compared with single agent, and it was dose-dependent (Figure 1b).Similar enhanced antiproliferative activity was confirmed in RPMI 8226 cell line, which carries 1q21 amplification (Figure 1c). We furthered to understand the mechanism of action (MoA) of this combination. In Figure 1d, Western blot analysis of RPMI 8226 cell line revealed that IKZF1 and IKZF3 proteins from the NF-KB pathway were downregulated by lenalidomide. And the decrease of MCL-1 protein and the strong induction of pro-death protein BAK were evident in the combination group of APG-2575 and lenalidomide, which helps to illustrate MoA underlying the synergistic effect of APG-2575 and lenalidomide in MM models. Conclusions In both cell lines and primary samples derived from MM patients, APG-2575 demonstrates cell death inducing activity as a single agent, and enhanced/synergistic effects when it combines with lenalidomide in RRMM resistant to lenalidomide and bortezomib. The combination decreases IKZF1, IKZF3 and MCL-1 proteins, and upregulates pro-death protein BAK, thus providing a strong rationale to combine BCL-2 inhibitor and lenalidomide to treat high-risk patient populations carrying 1q21 amplification. Disclosures FU: Ascentage Pharma (SuZhou) Co., Ltd: Other: research agreement contract . Yin:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment. Mao:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment. Deng:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment. Fang:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment. Yang:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests. Zhai:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests.

Background: Multiple myeloma (MM) is an incurable plasma cell malignancies despite the advent of numerously new drugs especially for high risk patients. Our previous study showed good response for the de novo high risk patients who received CD19 and BCMA-specific CART cell therapy after ASCT in the front line with mild CRS and other side effects (reported on the 2018 ASH meeting). To determine the best time to do ASCT and CART cell treatment for those patients, we retrospectively analyzed the patients' outcome according to their time to do autologous transplantation (NCT 03455972). Methods:The high risk MM patients defined in this study were in R-ISS stage III, IgD/IgE type, or with measurable EMD,or who only achieved PR or less after 4 cycles of triplet induction or relapsed. Lymphocytes were collected from PBSCs and cultured with an anti-CD3 monoclonal antibody to activate T-cell proliferation after stem cell collection. The cells were transduced with recombinant lentiviral verctors which respectively contained the anti-BCMA or anti-CD19 single chain variable fragment (scFv), the cytoplasmic portion of the OX40 and CD28 costimulatory moiety, and the CD3z T-cell activation domain. This is the new third generation CAR technique applied in clinic. BuCy or Melphalan were used as conditioning, followed by infusion of autologous stem cells. CART-19 (1×107/kg on d0) and CART-BCMA cells as split-dose (40% on d1 and 60% on d2) were infused directly on d14 to d20 after transplantation. The cytokine release syndrome (CRS) was graded according to the UPen cytokine release syndrome grading system. Neurotoxic side effects and other toxicities were assessed according to the CARTOX and CTCAE v 4.03. Plasma levels of IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma, and IL-17A proteins were determined with a cytokine kit. IMiDs alone were given as maintenance therapy. Responses were assessed by IMWG criteria. 10-color flow cytometry was used to monitor MRD regularly after CART treatment. The median of follow-up was 13 (1~23) months. Results: To date, 32 patients have completed the CART cells infusion (Table 1). The median age was 53 years with 24 male and 8 female. CRS occurred in 31 patients (97%) with grade 1 or 2 and just 1 patient (3%) with grade 3. Tocilizumab was used to treating only one patient with grade 3 CRS. Six patients needed to use low-dose vascular active drugs. Other acute and chronic toxicities were slight and reversible. The ORR was 100% (32/32) in this study, with 72% of patients achieved CR or above. There was no TRM or neurologic complications or administration of corticosteroid. All patients were divided into three groups according to their time to transplant. Group 1 underwent ASCT and CART cell treatment as first line therapy; Group 2 underwent ASCT and CART cell treatment at second line because of induction failure or re-induction after PD or relapse; Group 3 underwent salvage ASCT and CART treatment at third line or more after disease progress or relapse.With a median follow-up of 13 months, the latest response of CR and above were 78% in group 1, 100% in group 2 and 44% in group 3. Except the group 3 patients, MRD negativity in BM of the other two groups increased continuously after CART therapy, and some patients achieved MRD negativity at the level 10-6 (shown in Table 1). Patients in group 1 and 2 were in continuous response but 5/9 (56%) patients relapsed in group 3 and 2 patients died of disease. The median PFS and OS of the patients in three groups were all not reached but 1-year PFS was 100%, 100%, 68% for group1, 2, 3 respectively (p Conclusions: Combined infusion of anti-CD19 and anti-BCMA CART cells after ASCT for high risk MM was safe and effective, especially as conjunction therapy to early or later transplant at front line even with primary resistant disease or early disease progress. For those RRMM patients, CART cell therapy followed by ASCT seems to be better to prolong patients' PFS than CART treatment alone with FC chemotherapy reported in our another study (NCT 03196414). Disclosures No relevant conflicts of interest to declare.

Background Deregulation of histone acetylation has been recognized to serve a critical role in the pathogenesis of multiple myeloma (MM), which histone deacetylase (HDACs) are overexpressed in plasma cells derived from patients with MM. Therefore, HDACs may promise targets for MM therapy, and panobinostat was approved by the FDA for the treatment of relapsed/refractory MM in 2015. Chidamide, a novel oral benzamide type HDAC inhibitor independently developed in China and approved as peripheral T-cell lymphoma, selectively suppresses the activity of class I HDACs. Studies have shown that chidamide can enhance cytotoxic effect of bortezomib or lenalidomide on MM cells in vitro, which suggested a synergistic combination of chidamide with bortezomib or lenalidomide at a low dose. This Phase I clinical trial was designed to investigate the efficacy and safety of dose-escalating chidamide with VRD as induction chemotherapy for newly-diagnosed high-risk multiple myeloma (MM) patients before autologous transplantation (NCT 04025450). Methods The de novo MM patients who had any one of the followings was defined as high-risk MM: a. high-risk cytogenetics including 17p-, t (4, 14), t (14, 16), t (14, 20), 1q gain, 1p-, double hit myeloma, triple hit myeloma. b. R-ISS stage III. c. IgD/IgE type. d. with measurable extra-medullary plasmacytoma. e. peripheral blood clonal plasma cell≥0.165% by 10-colour flow cytometry. Chidamide at 4 dose levels (15mg/20mg/25mg/30mg d0,3,7,10) were administered to 12 patients with VRD (bortezomib 1.3mg/m2 d1,4,8,11, lenalidomide 25mg d1-14, and dexamethasone 20mg/d d1-2,4-5,8-9,11-12), every 21 days for 4-cycle induction therapy. Safety, DLT and efficacy of Chi-VRD were observed. Pain sore before each cycle and the whole body DWI-MR before and after 4-cycles were done to see whether improvement in osteodynia and sclerotin reparation of patients. All patients will be collected autologous stem cell to see whether there is effect of the regimen on stem cells after 4-cycle induction therapy. Results The median age of these 12 patients was 57.5 (45, 65), 50.0% was male and 25% (3/12) patients had renal insufficiency with creatinine≥177umol/l or Ccr≤40ml/min. 2 patients were R-ISS stage III; 4 had measurable extra-medullary plasmacytoma; 7 had circulating plasma cells ≥0.165%; and one had t(4;14). The total adverse events were listed in the table below (table1). The main treatment-related adverse events were hematological toxicity, hepatotoxicity, edema, deterioration of renal function and heart failure. Two patients with renal insufficiency had to stop this induction therapy, one for serious adverse event of acute heart failure and acute renal failure at the first cycle in the 20mg dose group and another one for intermittent medication in the 15mg group. All patients had osteodynia relief. Among the 9 patients who have had response evaluation, the ORR was 100% and 77.8% (7/9) patients had gotten very good partial response (VGPR) or better after one cycle. Conclusion This was the first report of ChiVRD induction treatment for newly diagnosed high risk MM. The preliminary results of Chi-VRD suggested excellent efficacy with rapid response. The most common adverse events were hematological toxicity and hepatotoxicity. No dose limiting toxicity (DLT) was observed at 4 dose levels. Hematological toxicity and hepatotoxicity may increase with the dosage increase, but could be quickly controlled. Although chidamide does not affect renal function itself, patients with renal insufficiency may have more adverse reactions that may need dose adjustment. Updated results with comparison between VRD and Chi-VRD will be presented at the following phase II trial. Disclosures No relevant conflicts of interest to declare.

Background: Relapsed and/or refractory multiple myeloma (RRMM) has a very poor prognosis, especially for chinese patients with limited therapeutic options. Chimeric antigen receptor transduced T cells (CARTs) had been approved to be one of the rescue strategies for malignant B cell hematological tumors. CARTs targeting B-Cell Maturation Antigen (BCMA) were effective against RRMM in recent published clinical studies. CD19 is expressed by B cells before terminal differentiation into plasma cells and is associated with the enhancement of tumor-propagating and drug-resistance properties of myeloma. Thus, CD19 is also a potential therapeutic target. To our knowledge, we firstly designed the clinical study to evaluate the safety and efficacy of sequential infusion of CD19 and BCMA-Specific CARTs for RRMM patients (pts) (NCT 03196414). Our initial results showed this stragety had substantial anti-myeloma activity and well tolerated toxicities, which had been released at the 59th ASH meeting. Here, we will report the latest clinical data of a total of 28 RRMM patients receiving combined autologous CARTs infusion. Methods: Human T cells were collected from autologous peripheral blood mononuclear cells (PBSC). CART production was performed by the Unicar-Therapy Bio-medicine Technology Company (Shanghai, China). In this trial, RRMM pts firstly receive FC regimen as lymphodepleting conditioning , then were infused into CART-19 (1×107/kg on day 0) and CART-BCMA (total dose range: 2-6.8×107/kg) cells as split-dose infusions (40% on day 1 and 60% on day 2). After one month from CARTs infusion, some pts were adminstrated IMiDs for maintence therapy after hematopoietic recovery, including oral thalidomide 50mg/d or lenalidomide 10mg/d. This trial design and observation was seen in Blood,2017,130(Suppl.):506.The median follow-up time was 16 (3-28) months. Results: By January 2019, 28 pts were enrolled in this clinical trial. Among them, 23 (82.1%) pts were males and 5 (17.9%) pts were females. The median age was 57.5 (range: 42-69) years old. All pts were resistant to proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), or both. These pts had received an average of 3 (2-8) lines of therapy prior to enrollment. The most common adverse event of CART therapy was acute cytokine release syndrome (CRS), which occurred in 28 pts (100%). 19 pts (67.9%) were evaluated grade 1-2 CRS. 7 pts (25.0%) were evaluated grade 3 CRS, and 2 pts (7.1%) were grade 4. High-grade CRS was associated with elevated levels of IL-6, IFNγ, IL-10 and CRP, especially IL-6 upgradation to thousands of times the baseline. Other toxicities within two weeks of CARTs infusion included fatigue (n=28; 100%), cytopenia (n=28; 100%), anemia (n=28; 100%), prolonged APTT (n=23; 82.1%), elevated creatinine (n=13; 46.4%), gastrointestinal reaction(n=9; 32.1%), elevated transaminase (n=9; 32.1%). Notably, one patient (CRS grade 4) developed grade 4 CRES who exhibited generalized seizure. But this life-threatening complication was quickly relieved after corticosteroids and sodium valproate administration. Two pts (7.1%) had HLH/MAS. No fatal or severe adverse events emerged after two weeks following the infusion. Chronic side effects included chronic diarrhea, hematocytopenia, mild infection, grade ≤2 bilirubin and/or transaminase elevation, hypogammaglobulinemia, etc. No treatment related mortality occurred in this group of pts. Among the 28 pts who completed the CARTs infusion, 27 pts were monitored at predetermined time points and one patient lost follow-up. The overall response rate was 92.6%, and 88.9% of the pts were above PR. 11 pts (40.7%) were CR or sCR, 8 pts (29.6%) were VGPR, 5 pts (18.5%) were PR and one (3.7%) was MR. The remaining 2 pts, one (3.7%) was evaluated as SD and another (3.7%) was PD. 4 pts died from myeloma progression during the follow-up. Of those pts, the median PFS was 8 months. The median OS was 16 months. Conclusions: Combined sequential administration of CART-19 and CART-BCMA cells can be manufactured from heavily-treated MM pts, and could elicit sustained remission for RRMM pts. Toxicities can be well tolerated. CARTs early expansion and persistence in vivo post infusion may be predictive of clinical outcome. How to prolong the survival time of CARTs in vivo is one of the subjects worth studying in the future. Disclosures No relevant conflicts of interest to declare.

Background: Multiple myeloma (MM) is an incurable plasma cell malignancies despite the advent of numerously new drugs. Survival was poor particularly for high risk patients such as R-ISS stage III. The preliminary data from our center showed that the median PFS after auto-HSCT was 24 months for patients with R-ISS III stage, while 17 months for patients that achieved PR or less after induction. Chimeric antigen receptor (CAR)-transduced T cells is a promising strategy for cancer immunotherapy. Our previous study showed good response for RRMM patients after CD19 and BCMA-specific CART therapy without severe CRS and other deadly side effects. To improve the survival of high risk patients, this study was designed to observe the safety and efficacy of combined infusion of CD19 and BCMA-specific CART cells after autologous transplantation (SZ-MM-CART02 study, NCT 03455972). Methods:18-65y NDMM in R-ISS stage III, or who only achieved PR or less after 4 cycles of PAD triplet induction were enrolled with serum creatinine (Cr) Results: To date, 9 patients have completed the CART cells infusion (cohort 1). All cases expressed BCMA >50% without CD19 expression on MM cells. CRS occurred in 9 patients (100%) grade1 or 2 associated with fever(n=9), fatigue (n=9), elevated IL-6 and CRP (n=9), elevated ALT (n=1, grade 1). Two patients needed to use low-dose vascular active drugs (pts 04 and 07). Other toxicities to date included coagulopathy (n=6, grade 1 for 4 pts and grade 2 for 2 pts), elevated troponin T (n=4, grade 1), and atrial flutter (n=1). There was no serious CRS or neurologic complications occurred in this group of patients. The ORR was 100% with all patients were monitored for a period of more than 2 months, which may be eventually further improved. There were 2 CR, 1 VGPR, 4 PR, 2 SD after induction; 3 CR, 2 VGPR, 4 PR after APBSCT; 3 CR, 6 VGPR after CART therapy. MRD negativity in BM increased from 37.5% after transplantation to 66.7% after CART therapy latest. Four patients (pts 02, 03, 06 and 07) obtained partial PR after transplantation, and got VGPR after CART cells infusion. We found dramatic in vivo CART expansion that median of peak value of CART copies was 1059.54 folds (ranged from 536.90 to 10997.93 folds) which was 100 folds to that with RRMM patients in our previous study. Conclusions: Tandom autologous transplantation and combined infusion of CART-19 and CART-BCMA cells could be another choice of consolidation treatment for high risk MM patients. Toxicities to date including CRS and organ function impairment seemed to be mild and reversable. It is worthy of further study to compare DFS, OS between single autologous transplantation and tandom transplantation with CART therapy. Immune environment in high risk patients with multiple myelomaI remodelled by auto-HSCT may contribute to more rapid expansion of CART cells than that in RRMM patients, suggesting that the extent of CART expansion depends more than tumor burden. Table Table. Disclosures No relevant conflicts of interest to declare.

Abstract 5217 Objective: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare and distinct type of T-cell lymphoma. The objective of this study was to explore the clinical presentation, treatment, and prognosis of patients with SPTCL. Methods: Twelve cases of SCPTCL, treated in our hospital between June 2005 and June 2010, were included in this study. Their clinicopathological data were reviewed and analyzed retrospectively. Results: The median age at diagnosis was 41 years (range 25–69 years) and 7 (58%) were women. 9 cases had a CD3+, CD4-, CD8- phenotype; 2 cases, a CD3+, CD4-, CD8+ phenotype; and 1 case, a CD3+, CD4+, CD8- T-cell phenotype. In all cases, strong expression of cytotoxic proteins (granzyme B, TIA-1, perforin) was observed. CD56 was expressed in 8 of 12 cases. 4 patients had presented with solitary or localized skin lesions. Ulceration was observed in 3 patients. B symptoms, such as fever, chills, night sweats, and weight loss, had been recorded in 7 of 12 patients. Laboratory abnormalities, mainly anemia, leucopenia, thrombocytopenia or combined cytopenias, and elevated liver function tests and lactate dehydrogenase, were reported in 4 patients. Bone marrow examination showed histiocytic hyperplasia, hemophagocytosis, or decreased cellularity in 3 cases, but no evidence of lymphoma. A HPS was diagnosed in 4 of 12 patients (33%), and was fatal in 2 of them. Four patients presenting with solitary or localized skin lesions had been treated with radiotherapy (2 cases) or surgery (2 cases). All 4 patients reached complete remission and only 1 of them showed a skin relapse, which was treated successfully with radiotherapy again. Eight patients with diffused lesions were treated with chemotherapy (CHOP or CHOP-like courses). After initial treatment 5 (63%) of 8 patients had developed new skin lesions, and 2 of them had developed extracutaneous localizations. Then the 3 of the relapsed patients were treated with autologous stem cell transplantation, all of whom obtained complete remission. At the time of last follow-up (median follow-up: 34 months; range: 10–60 months), 5 patients are in complete remission, 4 patients have ongoing skin disease, while 3 patients have died, 2 of the complications of HPS or therapy-related side effects and 1 of unrelated disease. The 3-year OS and DSS of the patients were 75% and 42%, respectively. Patients without HPS had a significantly better 3-year OS (88%) than patients with HPS (50%; P Conclusion: SPTCL seems to be a kind of heterogeneity disease. The factors associated with an unfavorable disease course were: diffuse lesions, a low white blood cell count, elevated lactate dehydrogenase, and combine with HPS. Autologous stem cell transplantation may improve the overall survival of high risk patients. Disclosures: No relevant conflicts of interest to declare.

Abstract 4461 Background WT1 is a panleukemic marker that is expressed in 90% of acute leukemias and has been used as MRD marker after chemotherapy or transplantation. However, the threshold of WT1 to predict relapse and outcome in acute leukemia (AL) patients post transplantation has not been well studied. Objective We evaluated the predictive value of quantitative Wilms’ tumor gene (WTl) assessment for relapse following hematopoietic stem cell transplantation (HSCT) in patients of AL. Methods The quantitative assessment of WT1 expression by real-time quantitative PCR (RQ-PCR) was measured in 63 AL patients (pts) with 326 bone marrow samples at the different time points post transplant. ROC (Receiver Operating Characteristic) curve was used to determine the WT1 threshold in order to predict clinical relapses. Furthermore, AL patients were divided into WT1 positive and negative groups according to the threshold of WT1, and the clinical outcomes of these patients post transplant were analysed retrospectively. Results BM samples from 19 pts who relapsed post transplanted showed significantly higher WT1 expression levels compared to the samples from 44 pts in remission (P585,n=21) and the negative group (≤585,n=42). The WT1-negative group had longer relapse- free survival (RFS) (P Conclusion Our data suggest that, in the HSCT setting, the sequential and quantitative analysis of WT1 may be useful as a leukemia marker for monitoring MRD, and predicting AL relapse post transplant. Disclosures: No relevant conflicts of interest to declare.

Abstract 658 Background Relapse remains a major cause of failure for allogeneic stem cell transplantation (allo-HSCT). Donor lymphocyte infusion (DLI) is routinely employed as salvage for patients who relapsed after allo-HSCT. In order to improve the graft versus leukemia (GVL) effect of DLI, we investigated the efficacy and safety of combining interferon-α with DLI (aDLI) in patients with high risk acute leukemia who relapsed after allo-HSCT, and compared the efficacy, toxicity and leukemia free survival (LFS) of aDLI and traditional donor lymphocyte infusion(tDLI)in our transplantation center. Methods Sixteen acute leukemia patients were enrolled in this study. All patients were treated with interferon-α-2b therapy at a dose of 3×106U/day subcutaneously for 5 days followed by G-CSF mobilized donor peripheral stem cell infusion. IFN-α treatment continued until complete remission or development of graft-versus-host disease (GVHD). We coined the term “aDLI” for this novel treatment protocol. The median duration of interferon-α treatment was 17 (range, 5–50) days, and the median CD3+ cells dose was 9.25×107/kg(range, 4–20×107/kg)of recipient weight. Bone marrow smear, real-time PCR, STR-PCR,FISH,cytogenetic analysis and flow cytometry were used to monitor engraftment and minimal residual disease. In parallel, we retrospectively analyzed the results of tDLI for 14 acute leukemia patients with hematological relapse post allo-HSCT treated in the same period in our transplantation center, and compared the efficacy, toxicity and LFS of tDLI with aDLI. Results Patients treated on the aDLI protocol included 9 ALL and 7 AML, with a median age of 26.5 years. Fourteen of 16 patients had high risk acute leukemia: 3 patients with Ph+ ALL, 6 patients relapsed after CR1, 4 patients had complicated chromosome abnormality, and 1 patient had testicular leukemia. The median relapse time was 5.5 (range, 1–25) months post transplant. Salvage chemotherapy was administrated in 7 patients before aDLI, with only 3 patients achieved CR. The overall complete remission (CR) rate for aDLI protocol was 75% (12/16), with CR rate of aDLI alone without chemotherapy at 66.7% (6/9). The median time from aDLI to bone marrow CR was 7(range, 6–14)days, and the median time to molecular complete remission (MCR) and full donor chemerism (median level was 96.3%) in responsive patients was 2 weeks post DLI. With a median follow-up of 5.5 (range, 1–34) months, 7 patients were alive with durable MCR. Two-year LFS was 50%. Treatment related toxicities included reversible episode of fever, GVHD and myelosuppression. The tDLI group had similar demographic characteristics with respect to age, disease subtypes, transplant and relapse history. Compared to tDLI, the aDLI protocol had higher CR rate (75.0% vs 14.3%, p =0.001), faster response (median time to obtain BM CR and full donor chimerism were 7 days vs 23 days, and 30 days vs 60 days respectively), higher incidence of acute GVHD (56.3 % vs 27.3%, p=0.05), and significant better 2-year LFS(50.0% vs 7.1%,p=0.05. Importantly, there was no significant difference between the two groups with respect to the incidence of pancytopenia (53.8% vs 75%, p>0.05) and treatment related mortality(18.8% vs 7.1%, p>0.05). Conclusion Interferon-α-2b in combination with donor lymphocyte infusion appears to induce rapid and durable remissions in high risk acute leukemia patients who relapsed following allo-HSCT, with acceptable treatment-related toxicity. This novel adoptive immunotherapeutic strategy warrants additional studies in allo-HSCT settings Disclosures: No relevant conflicts of interest to declare.

Abstract 4599 Background: POEMS syndrome is a multisystem disorder associated with plasma cell dyscrasias which characterized by polyneuropathy (P), organomegaly (O), endocrinopathy (E), serum M-protein (M), and skin changes (S). Recently, we successfully treated two POEMS syndrome patients by using bortezomib-based regimen(VDD) and followed by autologous peripheral blood stem cell transplantation (APBSCT) with bortezomib combined with high-dose melphalan(Mel) conditioning regimen. Methods: According to the latest Mayo Clinic criteria, two patients’ diagnosis of POEMS syndrome could be comfirmed. Both of them had no response to the classical treatments, but achieved near complete remission(CR) after 4 cycles and 1 cycle of VDD respectively(Bortezomib 1.3–1.6 mg/m2/w×4 weeks; 40 mg of Liposomal doxorubicin on the fourth day of the first week; and 10 mg of dexamethasone during the initial 4 days of first cycle. Each course was at 21 days interval). Then, autologous peripheral blood stem cell collection was performed sucessfully (2.16×106/kg and 3×106/kg respectively) after mobilization by cyclophosphamide (3g/m2/d for 1 day) with subcutaneous G-CSF. APBSCT were performed approximately 1 month after stem cell collection. Two patients were conditioned with Bortezomib 1.6mg/m2(d-13,d-6,d+1,d+7)+Mel 200mg/m2(d-3)and Bortezomib 1.3 mg/m2(d-8,d-1,d+6,d+13)+ Mel 200mg/m2(d-2) respectively. Results: No toxic death or serious adverse effects occurred during APBSCT. Neutrophil and platelet recoveried at +10d, +27d and +7d, +20d respectively. Only case 1 patient developed mild hypoxemia during neutrophil engraftment period, but was successfully treated with corticosteroid and antibiotic therapy. The case 2 presented mucositis, diarrhea and nausea during neutropenic peroid. A follow-up period were 12 and 6 months respectively. Both of them achieved continuous CR. There was a dramatic improvement in clinical symptoms and serum VEGF levels in all two patients post VDD treatment including organomegaly (splenomegaly), M-protein, pericardiac/pleural effusion,ascites and polyneuropathy. Conclusion: This is the first report of POEMS patients treated by APBSCT with bortezomib and high dose Melphalan conditioning regimen. Our results suggest that Bortezomib is a new effective and relative safe therapeutic option for POEMS syndrome not only in the conventional treatment but also in APBSCT procedure. Disclosures: No relevant conflicts of interest to declare.

Abstract 3550 Background and Objectives Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still a major cause for the failure in treatment. It has been shown that there was a closely relationship between the level of minimal residual disease (MRD) and relapse in acute leukemia (AL) patients; However, the application of multiparameter flow cytometry (MFC) for MRD assessment in high risk patients with AL who undergoing allo-HSCT is little concerned. We retrospectively analysed the serial results of MRD of 52 high risk patients with AL to evaluates the prognostic value of MRD pre and post transplantation. Methods 52 patients with a median age of 29 (13–55) years have been enrolled on this study in our hospital from January 2003 to September 2008.Diagnoses included AML (n=27) and ALL (n=25). The patients had been analyzed retrospectively the level of MRD pre-(day-30)and post-HSCT(day+30 and +100)using three color FCM with CD45/SSC gating and a comprehensive panel of monoclonal antibodies, at least one leukemia associated aberrant immunophenotype (LAIP) at diagnosis. According to the cutoff value 0.1%, two groups were defined based on the level of patient's MRD level< (low level group) or >= (high level group) 0.1%. Results The median follow up were 23 (range 1–60) months. 1.MRD level declines significantly (P=0.03) post transplant. 2. There were significantly difference between low level and high level group at day -30 before transplant with 3 years event free survival(EFS) and relapse free survival (RFS)(77.4% and 88.4% vs. 22.3% and 25.7%, p=0.007and p=0.001 respectively). 3. Concerning about MRD at day +100 after transplant, outcome was significantly better among patients with low level MRD group versus high group including 3 years OS,EFS and RFS(84.2%, 79.5% and 89.5% versus 22.9%, 9.5% and 11.2%).4. The median time from high level MRD detected first time to clinical relapse was 2.5 (range from 1 to 33) months in relapsed patients. 5. The patients with cGVHD had better 3 years OS and EFS than that without cGVHD(86.3% vs 12.1%, p Conclusions MRD monitoring pre- and post-transplant is an important tool to predict the outcome of transplantation for patients with high risk AL. The MRD check point at day +100 should be considered crucial for subsequent therapeutic decisions after allogeneic transplantation. Disclosures: No relevant conflicts of interest to declare.

Abstract 4107 Objectives To determine the pulmonary pathological changes in patients of hematological malignancies with pulmonary complications using surgical or thoracoscopic technologie. Methods 17 hematological malignant patients who underwent surgical treatment were evaluated retrospectively in our study. Pulmonary infection was presented in 14 cases following chemotherapy, and lesions can not be completely absorbed after a broad-spectrum anti-bacterial and anti-fungal treatment. Furthermore, computerized tomographic scanning showed that there remained several kinds of localized lesions. Subsequently, all the 17 patients underwent open lung or thoracoscopic biopsies (lobar, partial, or wedge resection). The pathological changes of all the surgical specimens were examined postoperatively by standard hematoxylin and eosin staining. Results Pathological examination confirmed: Aspergillus infection in 9 patients, sub-acute inflammation (fibrosis and hematoma formation) in 3 patients, pulmonary infarction with granulomatous tissue in the periphery in 1 patient, granulomatous inflammation with calcified tubercle in 1 patient, alveolar dilation and hemorrhage, interstitial fibrosis and focal vasculitis in 1 patient, intercostal neurilemmoma in 1 patient, and moderate-differentiated adenocarcinoma accompanied by intrapulmonary metastasis in 1 patient. And several operative complications (1 case of fungal implantation, 3 cases of pleural effusion and adhesions and 2 cases of pulmonary hematoma) were occurred. The coincidence rate of pre- and post-operative diagnosis was 9/14 (64.3%). After surgery, 8 patients were received hematopoietic stem cell transplantation (HSCT, allo-gene or autologous), in which 7 cases were succeeded. Following the effective secondary antifungal prophylaxis,4 of 5 patients of aspergillosis were succeeded in transplantation free from mycotic relapse,just one patient was dead from fungal relapse. Conclusion Hematological malignancies with certain pulmonary complications, that is, persistent and/or medical-management-resistant pulmonary infection, hemoptysis, or lung diseases of diagnosis unknown, should be treated in time by surgical resection to effectively eliminate the residual disease and to achieve definitive diagnosis, so as to create a prerequisite condition for the following treatments. Moreover, the secondary antifungal prophylaxis could provide positive roles in protecting patients scheduled for chemotherapy and/or HSCT. Keywords hematological malignancies; immunocompromise; pulmonary aspergillosis; pulmonary resection; histopathology ; secondary antifungal prophylaxis Disclosures: No relevant conflicts of interest to declare.

Abstract 4966 POEMS syndrome is a rare multisystem disease characterized by polyneuropathy (P), organomegaly (O), endocrinopathy (E), serum M-protein (M), and skin changes (S). Owing to the fairly little refined mechanisms underlying the pathogenesis of POEMS syndrome, standard and general-accepted regimens have not been established to date. Recently, we successfully treated a POEMS syndrome patient who was unresponsive to conventional therapies by using bortezomib-based regimen. This 37-year-old patient represented a number of typical manifestations including: 1) paresthesia, 2) increased level of IgA » type of M protein, 3) elevated concentration of serum VEGF (vascular endothelial growth factor), 4) splenomegaly, gynaecomastia, limbs edema, hydropericardium, hydrothorax, and plethora. According to the latest Mayo Clinic criteria, the diagnosis of POEMS syndrome could thus be comfirmed. After several courses of classical regimens [VAD (Vincristine, doxorubicin, dexamethasone), CMP (cyclophosphamide, melphalan and prednisone) and AD (doxorubicin and dexamethasone)], the patient poorly responded with only slight improvement and failed to achieve remission. Following the patient's informed consent and Ethics Committee approval, a tentative VDD regimen was carried out. The details were as follows: Bortezomib, at a dose of 1.3-1.6 mg/m2 (initial cycle: 1.3 mg/m2 in the first week, 1.6 mg/m2/w in following three weeks; next three cycles: 1.6 mg/m2/w×4 weeks in each cycle); 40 mg of Liposomal doxorubicin on the fourth day of the first week; and 10 mg of dexamethasone during the initial 4 days of first cycle. Each course was at 21 days interval. Following four cycles of VDD, the patient acquired remarkable improvement (concerning neurological disease, skin changes, clonal plasmacytosis, and organomegaly) and finally achieved complete remission. To our knowledge, It should be the first time in the world that the bortezomib-based new strategy could be applied effectively against the POEMS syndrome. Further, we could speculate that the VDD regimen would be a potent candidate in the treatment of POEMS syndrome, at least in the conventional therapy-resistant condition. Disclosures No relevant conflicts of interest to declare.