bluuebunny/crossref_metadata_2025 huggingface dataset:
PF812 INTRAVENOUS IRON SUPPLEMENTATION PROTOCOL FOR POST‐PARTUM ANEMIA
Authors: Volpato E. , Cuppari I. , Lissoni D. , Pugliano M.T. , Crocchiolo R. , Rossini S.
Published: June 2019

Background:

The World Health Organization (WHO) determines as post‐partum anemia values of harmoglobin (Hb) less than 10 g/dl. In most cases, it's an iron deficiency anemia and affects about the 27% of new mothers and has as a consequence a strong socio‐economic impact. One of the most important causes is the post partum haemorrhage (PPH), that's to say 500 ml of blood loss in the first 24 hours after a vaginal delivery or more than 1000 ml after a caesarean section. Nowadays PPH is one of the most common causes of mortality and morbidity rate among obstetric population and its frequency is between the 5% and the 22 % of the total deliveries.

Aims:

The objective of the present study is to determine the efficacy of an iron supplementation protocol for post‐èartum anemia.

Methods:

Our protocol provides a valuation of Hb in the post partum period. When Hb is greater than 8..5 g/dl, the new mother can be discharged from hospital and is treated by oral iron supplementaion with ferrous sulfate but it will be necessary to control the Hb value after 30 days. In case of HB belove 8..5 g/dl, parenteral iron is used (iron carbossymaltose) in the Obstretician Unit, then there will be a new assessment after 10/15 days at Service of Immunohaematology and Trasfusional Medicine to decide if to go on supplementation.

Results:

From 01/06/2017 to 31/12/2018 36 new mothers, average age 34 years (range 23 ‐ 43) have been enrolled. During the recovery, 34 new mothers have been treated with ferric carboxymaltose: 26 with a dosage of 500 mg and 8 with 1 g. Among these 34 women, 4 have been trasfused after a severe PPH and concomitant thalassaemic trait. Only 2 of the new mothers have been discharged with ferrous sulfate. At discharge, average Hb was 7.3 g/dl. At first access in Transfusional Center, the average Hb value was 10.8 g/dl with a medium delta of 3.5 g/dl. According to the hemoglobin values, 18 new mothers have continued oral iron therapy, 14 have been treated with ferric carboxymaltose and only 2 didn’t need therapy.

Summary/Conclusion:

Our protocol has been implemented thanks to the indications of National Blood Center about the PMB to ensure, through the multidisciplinarity, the transfusion appropriatness, the resource optimization and the improvement of the patient's outcome. The intravenous iron therapy with ferric carboxymaltose in new mothers suffering a severe iron deficiency anemia allows a fast rise of hemoglobin values and an improvment of psychophysical wellbeing of the new mother and a lowering of the number of blood transfusions.
S824 A PHASE 3 RANDOMIZED, OPEN‐LABEL, MULTICENTER STUDY OF ISATUXIMAB, POMALIDOMIDE, AND LOW‐DOSE DEXAMETHASONE VS POMALIDOMIDE AND LOW‐DOSE DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM)
Authors: Attal M. , Richardson P.G. , Rajkumar S.V. , San‐Miguel J. , Beksac M. , Spicka I. , Leleu X. , Schjesvold F. , Moreau P. , Dimopoulos M.A. , Huang J.S.‐Y. , Minarik J. , Cavo M. , Prince H.M. , Mace S. , Corzo K.P. , Campana F. , Le‐Guennec S. , Dubin F. , Anderson K.C.
Published: June 2019

Background:

Despite recent advances, multiple myeloma (MM) remains incurable, and new treatment options are needed to continue to improve patient outcomes. This is the first randomized, phase 3 trial of an anti‐CD38 antibody in combination with pomalidomide (P) and dexamethasone (d) in RRMM.

Aims:

The primary objective of this phase 3 trial (NCT02990338) was to demonstrate progression free survival (PFS) improvement of isatuximab (Isa), a novel anti‐CD38 monoclonal antibody targeting a specific epitope, combined with Pd versus (vs) Pd in RRMM.

Methods:

Patients (pts) with RRMM who received ≥2 prior lines, including lenalidomide (len) and a proteasome inhibitor (PI), refractory to last therapy were enrolled. IsaPd arm received Isa 10 mg/kg IV weekly for first 4 weeks (wks), then every 2 wks. Both arms received approved schedules of pom and dex (4 mg PO days 1–21; 40 mg [20 mg if >75 yrs] PO or IV weekly) every 28 days until progression or unacceptable toxicity.

Results:

307 pts (154 IsaPd, 153 Pd) were randomized and analyzed (ITT). Patient characteristics were well balanced across arms. Median age: 67 (36–86) yrs; median prior lines of therapy: 3 (2–11); estimated GFR: <60 ml/min in 33.9% pts; 92.5% refractory to len, 75.9% to PI; and 19.5% pts had high‐risk cytogenetics. At median follow‐up of 11.6 months (mos), median PFS was 11.5 mos IsaPd vs 6.5 mos Pd; HR 0.596 (95% CI 0.44–0.81), P = 0.001. PFS benefit was consistent across all major subgroups. ORR (≥PR) was 60.4% IsaPd vs 35.3% Pd, P < 0.0001. VGPR rate or better was 31.8% IsaPd vs 8.5% Pd, and MRD negativity (NGS, 10−5) was seen in 5.2% IsaPd pts vs 0% Pd. At analysis date, overall survival (OS) was immature (99 events) but a trend to OS improvement in IsaPd (vs Pd) was observed (HR 0.687; 95% CI 0.461–1.023). Median treatment duration was 41 wks IsaPd vs 24 wks Pd; median Isa infusion (inf.) duration was 3.3 h at 1st inf. and 2.8 h at subsequent inf. Grade ≥3 AEs were observed in 86.8% IsaPd vs 70.5% Pd; 7.2% IsaPd and 12.8% Pd pts discontinued due to AEs; 7.9% IsaPd and 9.4% Pd pts died due to AEs. Inf. reactions were reported in 38.2% (2.6% grade 3–4) IsaPd. Grade ≥3 infections were seen in 42.8% IsaPd and 30.2% Pd, grade ≥3 neutropenia in 84.9% (febrile 11.8%) IsaPd and 70.1% (febrile 2.0%) Pd.

Summary/Conclusion:

Isatuximab in combination with pomalidomide and dexamethasone significantly improved PFS and ORR vs pomalidomide and dexamethasone, with a manageable safety profile. Isatuximab in combination with pomalidomide and dexamethasone is an important new treatment option for the management of RRMM.
PS953 SURVIVAL OUTCOME OF SECOND ALLOGENEIC‐HCT IN ADULT ALL PATIENTS WHO RELAPSED AFTER PREVIOUS ALLOGENEIC‐HCT
Authors: Yoon S.Y. , Yoon J.‐H. , Kim C. , Lee J. , MIn G.J. , Eom K.‐S. , Kim H.‐J. , Lee J.W. , Lee S.
Published: June 2019

Background:

Allogeneic hematopoietic cell transplantation (allo‐HCT) is a potentially curative option for adult patients with acute lymphoplastic leukemia (ALL). However, no standard therapy is elucidated for patients who relapsed after allo‐HCT.

Aims:

We analyzed patients treated with second allo‐HCT and tried to find out risk factors for survival outcomes.

Methods:

We retrospectively analyzed 35 adult ALL patients (median 35 years old, range 16–66) treated with second allo‐HCT in second remission from 2010 to 2017, all of them relapsed after previous allo‐HCT (median 12.8 months, range 2.9–99.4). After second remission, most patients underwent second allo‐HCT from available donor within 6 months, but some patients with Ph‐positive ALL responding to salvage tyrosine kinase inhibitors or with isolated EMR were delayed for second allo‐HCT.

Results:

Of 35 patients, 3 patients were T‐ALL, 16 were Philadelphia chromosome (Ph)‐negative, and 16 were Ph‐positive B‐ALL. Extramedullary relapse (EMR) were observed in 11 patients, and 5 of them were isolated EMR without hematological relapse. At the time of second allo‐HCT, 17 were in complete remission (CR) and 18 were in CR without full hematological recovery. Among 16 Ph‐positive ALL patients, 9 were in complete molecular response, 2 were in major molecular response, and 5 were in poor molecular response. After median follow‐up of 38.2 months (range 7.5–86.3), 3‐year overall survival (OS) and disease‐free survival (DFS) were 31.9% and 26.0%, respectively. Cumulative inicidence of non‐relapse mortality (NRM) and relapse (CIR) at 3 years were 29.1% and 45.4%, respectively. Acute GVHD was observed in 17 (12 with grade I‐II, 4 with grade III, 1 with grade IV) and chronic GVHD was observed in 14 (mild 7, moderate 4, severe 3) out of 31 patients who were alive at least 100 days after HCT. We identified late relapse > 6 months and early allo‐HCT within 6 months (48.1% vs. 12.5% ; HR = 0.27, 95%CI 0.1–0.7, p = 0.014) and chronic GVHD (49.0% vs. 27.8% ; HR = 0.28, 95%CI 0.1–0.8, p = 0.021) showed favorable 3‐year OS in the entire cohort. Among patients with Ph‐positive subgroup, post‐HCT complete molecular response was related with superior OS (66.7% vs. 0.0% ; HR = 0.09, 95%CI 0.01–0.69, p = 0.021).

Summary/Conclusion:

Our data suggested that second allo‐HCT might be a feasible choice for some patients relapsed after previous allo‐HCT as a curative treatment option when allo‐HCT is performed earlier in late relapse case. Safe salvage therapy and additional post‐HCT preemptive therapy should be considered for better transplant outcomes.
PS980 GRIK5 DRIVES SELF RENEWAL PATHWAYS IN HUMAN ACUTE MYELOID LEUKEMIA CELLS
Authors: Xia J. , Garg S. , He L. , Jagdhane P. , Carsten M.‐T. , Caroline P.
Published: June 2019

Background:

Acute myeloid leukemia (AML) is characterized by a block in differentiation and uncontrolled proliferation of immature hematopoietic precursor cells. Self‐renewing leukemia stem cells (LSCs) are supposed to initiate and promote the disease. In our previous study, we had identified a set of genes associated with high LSC frequency in normal karyotype AML. Among these, we identified the Glutamate receptor ionotropic, kainate 5 (GRIK5) coding for a transmembrane protein, which is known to be expressed in the central nervous system as a ligand‐gated ion channel receptor.

Aims:

In this study, we aimed to understand the functional role of GRIK5 in normal HSPCs and AML cells. In particular, we investigated how GRIK5 drives self‐renewal pathways in AML and whether GRIK5 might represent a novel cell surface target for anti‐leukemic therapy.

Methods:

We performed knockdown (KD) experiments using small hairpin (sh) RNAs to determine whether GRIK5 was essential for proliferation, differentiation, and survival of primary human cord blood CD34+ HSPCs, leukemic cell lines, and primary human‐derived AML xenograft cells. Furthermore, lentivirally transduced HSPCs and leukemia cells were analyzed in vitro for proliferative output, viability, immunophenotype, and colony formation potential. RNA sequencing (RNA‐Seq) and whole cell mass spectrometry followed by enrichment analysis were used to identify key signaling pathways affected by GRIK5 KD.

Results:

We found that knockdown of GRIK5 expression strongly impaired leukemic cell proliferation and totally abrogated human leukemic engraftment in immunocompromised mice. In the healthy system, however, GRIK5 KD predominantly reduced the proliferative output of more committed progenitors, while more immature HSPCs were less affected. RNA‐Seq data points towards a major involvement in several key self‐renewal pathways.

Summary/Conclusion:

Here we found that the surface receptor GRIK5 is overexpressed in the majority of AML samples compared to healthy HSPCs. GRIK5 plays a pivotal role in proliferation, differentiation, and engraftment capacity of primary human leukemia cells in xenotransplantation assays and might, therefore, be used as a novel therapeutic target for anti‐leukemic therapies.
PS1066 AXICABTAGENE CILOLEUCEL (AXI‐CEL) IN REFRACTORY LARGE B CELL LYMPHOMA: OUTCOMES IN PATIENTS ≥ OR < 65 YEARS OF AGE IN THE PIVOTAL PHASE 1/2 ZUMA‐1 STUDY
Authors: Neelapu S.S. , Jacobson C.A. , Oluwole O.O. , Munoz J. , Deol A. , Miklos D.B. , Bartlett N.L. , Braunschweig I. , Jiang Y. , Kim J.J. , Zheng L. , Rossi J.M. , Locke F.L.
Published: June 2019

Background:

Axi‐cel is an autologous anti‐CD19 chimeric antigen receptor (CAR) T cell therapy approved in the European Union and United States for the treatment of patients with relapsed or refractory large B cell lymphoma with ≥ 2 prior systemic therapies. In the 2‐year follow‐up of ZUMA‐1, the objective response rate was 83%, with a complete response rate of 58%, and 39% of patients were in ongoing response (Locke et al. Lancet Oncol. 2019).

Aims:

To assess efficacy and safety outcomes of axi‐cel in patients ≥ or <65 years of age from ZUMA‐1.

Methods:

Eligible patients with refractory large B cell lymphoma underwent leukapheresis and conditioning chemotherapy followed by a target dose of 2 × 106 anti‐CD19 CAR T cells/kg. The Phase 2 primary endpoint was investigator‐assessed objective response rate. Additional key endpoints were adverse events, overall survival, and levels of CAR gene‐marked cells in peripheral blood. Efficacy was evaluated for Phase 2 patients; safety was evaluated for all treated patients (Phases 1 and 2). Patients were analyzed by age ≥ 65 years vs <65 years.

Results:

As of August 11, 2018, 108 patients were treated. Patients ≥ 65 years (n = 27) vs <65 years (n = 81) had a median age of 69 years vs 55 years, respectively, and were 81% vs 63% male; 70% vs 36% had an International Prognostic Index score of 3–4, 59% vs 57% had an Eastern Cooperative Oncology Group performance status of 1, 67% vs 72% had ≥ 3 prior therapies, and median tumor burdens were 3790 mm2 vs 3574 mm2. Median follow‐up was 27.1 months for Phase 2 patients (n = 101). The objective response rate for patients ≥ 65 years (n = 24) and <65 years (n = 77) was 92% and 81% (complete response rate, 75% and 53%), respectively, with ongoing responses in 42% and 38% of patients (ongoing complete response, 42% and 35%). The 24‐month overall survival rate was 54% for patients ≥ 65 years and 49% for patients <65 years. Most patients experienced Grade ≥ 3 adverse events (100% of patients ≥ 65 years; 98% of patients <65 years), and 4% of each group (1/27 patients ≥ 65 years and 3/81 patients <65 years) died due to adverse events as previously reported. Grade ≥ 3 neurologic events and cytokine release syndrome occurred in 44% vs 28% and 7% vs 12% of patients ≥ 65 years vs <65 years, respectively. CAR T cell expansion by peak level (43 vs 35 cells/μL) or area under the curve (562 vs 448 days × cells/μL) was similar in patients ≥ 65 years vs <65 years, respectively.

Summary/Conclusion:

The 2‐year follow‐up of ZUMA‐1 demonstrates that axi‐cel can induce high rates of durable responses with a manageable safety profile for patients ≥ and <65 years. Axi‐cel offers substantial clinical benefit for older patients with refractory large B cell lymphoma who otherwise have limited treatment options.
PS1114 PATIENTS WITH GAUCHER DISEASE SHOW AN IMMUNE‐DYSREGULATION PATTERN SECONDARY TO A DEFECT OF APOPTOSIS
Authors: Miano M. , Madeo A. , Cappelli E. , Fioredda F. , Palmisani E. , Terranova P. , Lanza T. , Vené R. , Vernarecci C. , Beccaria A. , Maggiore R. , Guardo D. , Dufour C. , Micalizzi C. , Di Rocco M.
Published: June 2019

Background:

Gaucher Disease (GD) is a congenital disorder secondary to GBA1 gene mutations that cause a defective function of the catabolic enzyme β‐glucocerebrosidase (GBA) and a progressive accumulation of its substrate‐ glucocerebroside (GC) in various organs, in particular in mononuclear phagocite system. Bone infiltration, hepatosplenomegaly and cytopenia represent the most common features of the disease. Since clinical manifestation can be subdolous, in some cases, phenotype can overlap with Autoimmune Lymphoproliferative Sindrome (ALPS). Nonetheless, GD patients were also shown to have hyperinflammatory features‐ secondary to machrophages engorgement and actviation‐ and an aspecific impaiment involving B, T and NK cells. In addition, some patients also showed more specific ALPS‐like immune‐dyregulation features suggesting an underlying apoptosis defect.

Aims:

To evaluate specific ALPS‐like immunological and serological pattern (Double Negative T‐cells, TCR alfa/beta B220, B‐memory cells, T‐regs/HLA‐DR ratio, IL‐10, IL‐18,) in a cohort patients with GD and to test apoptosis pathway function in those showing ALPS‐like features.

Methods:

All patients were diagnosed with GD by enzyme assay on lymphocytes culture or fibroblasts and by characterization of pathogenetic variants of GBA1. Lymphocytes subsets and ALPS‐related serum biomarkers (IL‐10, IL‐18, sFAS, Vit.B12) were analyzed in 41 GD patients followed‐up at Istituto Giannina Gaslini. Furthermore, in those patients who showed an ALPS‐like phenotype, apoptosis function was analyzed after FAS–induced stimulation of EBV‐immortalized B‐cells and Western blot analysis of CASP10, CASP8, and PARP proteins.

Results:

10/41 (24%) patients showed an ALPS‐like immunological pattern which was more frequent in naïve patients (p = 0.003) and in patients with an earlier onset of the diesease (p = 0.010). EBV‐immortalized B‐cells of 7 out of these 10 patients were further studied and all of them showed a defective FAS‐induced apoptosis and caspases activation. Fig 1 shows apoptosis evalutation of the selected population.

Summary/Conclusion:

To the best of our knowledge, this study shows for the first time that untreated subjects with early‐onset GD present an immune‐dysregulation pattern secondary to a defect of apoptosis as seen in ALPS patients. These results suggest that diagnostic work‐up of both diseases must take into consideration their clinical and biochemical overlap. Further studies are needed to evaluate the potential role of cell‐membrane lipids impairment on FAS receptor structure as a cause of such defect.

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PS1119 PNH CLONE SIZE BY FLOW CYTOMETRY AND ITS CORRELATION TO PIG GENE MUTATION
Authors: Jeong D. , Park H.S. , Choi S. , Seo H. , Kim S.‐M. , Im K. , Lim K. , Yun J. , Kim J.‐A. , Kim K. , Kim J.H. , Lee D.S.
Published: June 2019

Background:

Routine diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) is based on flow cytometric measurement of PNH clone in RBC and granulocyte. However there is no well‐established consensus on the clinically significant size of PNH clone.

Aims:

So we investigated whether quantitative results of PNH clone size measured by flow cytometry (FCM) correlate with mutant burden of PIG gene.

Methods:

A total of 89 specimens from 63 patients whose PNH clone size was ≥0.1% by FCM was enrolled. We performed ultra‐deep sequencing for PIGA, PIGM and PIGX genes on these 89 consecutive specimens. Also, we followed up 6 patients who were treated with Eculizumab and analyzed their laboratory changes including hemoglobin, lactate dehydrogenase level, PNH flow cytometry and PIG gene mutant burden. Treatment response was evaluated every 6 months.

Results:

Sixteen out of 63 patients had >10% granulocyte PNH clone and they all had PIG gene mutation. Fifteen (93.8%) had PIGA mutation and one (6.3%) PIGM mutation. Patients with >15% RBC PNH clone (n = 12) all had PNH‐related symptoms (p <0.001). Granulocyte clone size showed better correlation with VAF than RBC clone size (Granulocyte r = 0.61, p = 0.01, RBC r = 0.39, p = 0.14). On the other hand, RBC clone size was better reflective of PNH‐related symptoms with a cut‐off of 15% (p <0.001). We found no significant laboratory parameter for prediction of Eculizumab treatment response.

Summary/Conclusion:

Patients with >10% granulocyte PNH clone by FCM were always accompanied by PIG gene mutation. Those with >15% RBC PNH clone by FCM all had PNH‐related symptoms. Weak correlation between granulocyte clone size and VAF of PIG gene mutation implies that granulocyte clone reflects the real PNH clonal burden.

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PS1193 CHARACTERISTICS AND OUTCOMES OF THE TREATMENT PATIENTS WITH T315I MUTATION CML
Authors: Vlasova J. , Morozova E. , Barabanshikova M. , Gindina T. , Alyanskiy A. , Darskaya E. , Afanasyev B.
Published: June 2019

Background:

Resistance to tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukemia (CML) is frequently caused by point mutations in the BCR‐ABL kinase domain, including the gatekeeper mutant T315I, which confers a high degree of resistance to all currently approved tyrosine kinase inhibitors except ponatinib.

Aims:

To evaluate the results of different treatments in CML patients with mutation T315I.

Methods:

Retrospective analysis of 79 BCR‐ABLT315I ‐positive CML patients (pts) was done. Allogeneic bone marrow transplantation (allo‐HSCT) was made in 20 pts, 59 pts received only pharmacological therapy (41 pts received TKI as monotherapy or in combination with other drugs, 10‐ α‐IF, other 8 pts received hydroxyurea or chemotherapy). At the time of allo‐HSCT 6 pts were in CP 1, 7‐ CP≥2, 6 pts had AP and 3 pts were in BC. Median (Me) age at the time of mutation detected was 42 years (13–75) (38 years in HSCT‐group). In allo‐HSCT group 13 pts had unrelated donors, 13(65%) pts received more than 2 lines TKIs before HSCT. The number of points on EBMT scale: 3–4 points ‐ 16 pts, 5–7 points ‐ 6 pts. Conditioning regimen in 13 (70%) pts had reduced intensity. Me time to HSCT after T315I detection was 7 months (0–72).

Results:

Me follow‐up time after T315I detection was 21 months (1–100). 5‐years OS in whole group was 42%. According to multivariate analysis only CML phase at the time of mutation detection significantly affect to survival in whole group. All pts in BC (n = 7), 3 in HSCT group and 4 in non‐HSCT group, died within first year after T315I indication wherein Me survival time was 1,3 month. 5‐years OS in non‐HSCT group (n = 59) was 42% with Me survival time 2,8 years. 5‐years OS after allo‐HSCT (n = 20) was 37% with Me survival time 5 months. However, 7 pts live more than 2 years after allo‐HSCT, 2 ‐ more than 6 years. All living patients after allo‐HSCT are in deep molecular response. Pts in the 2nd CP have OS 47% (CI 95% 29–53%), p = 0.46. There was no significant difference in 5‐years OS between TKI (n = 41) and non‐TKI (n = 18) pharmacological therapy (non‐HSCT) groups (42% and 47% respectively, p = 0,53). In the group that received α‐interferon in the combination with other drugs (n = 10), the 5‐year OS is higher than in the group that did not receive interferon therapy (n = 49), 72% vs 45%, respectively (p = 0.21).

Summary/Conclusion:

Detection of T315I mutation in TKI‐resistant patients is extremely unfavorable factor for survival, and it is a great reason for switching to ponatinib or other new potential investigated drugs if possible. Allo‐HSCT is an effective method of treatment for this group of patients in case of good selection taking into consideration transplant risk, especially for patients in CP ≥2. The administration of pharmacological therapy in the 1st CP is an effective method of treatment, which allows to control the disease for a long time.
PS1223 INTERIM ANALYSIS OF A WT‐1 AND PRAME ‘FAST‐DC’ VACCINE SHOWS SAFETY AS ACTIVE IMMMUNOTHERAPY FOR THE PREVENTION OF AML RELAPSE
Authors: Fløisand Y. , Bigalke I. , Josefsen D. , Geiger C. , Pinkernell K. , Kvalheim G.
Published: June 2019

Background:

Patients with acute myeloid leukemia (AML), not eligible for allogeneic hematopoietic stem cell transplantation (HSCT), have a significant risk of disease relapse due to lack of long‐term disease control.

Aims:

To investigate the possibility of relapse prevention after initial chemotherapy, a safety and feasibility Phase I/II trial (NCT02405338) is currently being conducted using dendritic cells (DCs), generated with a rapid production protocol of 3 to 4 days. The manufacture uses RNA electroporation encoding the full‐length protein antigens PRAME (Preferentially expressed antigen in Melanoma) and WT‐1 (Wilm's Tumor‐1 Antigen) as well as a cocktail containing a TLR‐7/8 agonist for maturation. Data presented here reflect results of an interim analysis at the 1 year follow up time point, while vaccination continues until all patients reach the end of the trial at a follow up of 2 years.

Methods:

A total of 20 subjects (median age 59, range 24 to 73) with AML (risk groups good, intermediate, poor: 13, 5, 2), in morphologic complete remission or complete remission with incomplete hematologic recovery after induction or consolidation therapy, not eligible for allogeneic HSCT, were entered in the trial. Subjects had to be positive for WT‐1 with or without positivity for PRAME. DC vaccinations were carried out monthly, with a higher frequency within the first 6 weeks. AML diagnoses were established with a median of 9.8 months before the first vaccination (range 4.5 to 17.5 months), and the last chemotherapy infusion was performed at a median of 6.9 months (range 2 to 14.8 months).

Results:

The manufacture of the DC vaccine in these chemotherapy‐pretreated subjects was feasible for all 20 patients and aliquots of 5 to 10 x 106 cells were used per vaccination. The vaccinations were well tolerated with no serious adverse events (SAEs) related to the treatment. The most common adverse events (AEs) were injection site related, accounting for 35% of all AEs and were mild in nature (Grade 1). A total of 3 grade 3 adverse events, unlikely or not related to the treatment, were recorded: one Herpes zoster infection, one upper respiratory tract infection and 3 decreases in platelet counts. All three platelet count decreases were due to relapses of the leukemia.

After a 12‐months treatment period, the overall survival was 89% (18 of 20 patients, 95% confidence interval: 61 to 97%) and the progression free survival was 60% (12 of 20 patients, 95% confidence interval: 36 to 78%). Most relapses, 5 out of 8, occurred within the first 80 days after the start of the vaccination, out of which the 2 deaths were in patients with relapses on days 45 and 64, which could point to a starting relapse upon entering the study.

Summary/Conclusion:

In summary, at a follow up time of 1 year, DC vaccination against WT‐1 and PRAME appears to be safe and feasible for use in the prevention of AML relapse.
PS1228 SF3B1 KNOCKDOWN AT EARLY ERYTHROPOIESIS INDUCED CELL APOPTOSIS BY USING A TET‐ON LENTIVIRAL VECTOR
Authors: Huang Y. , Wu X. , Sun L. , An X.
Published: June 2019

Background:

SF3B1 has been drawing great interests of scientists due to their significantly high mutation frequency in one kind of hematological disease Myelodysplastic syndromes‐Refractory anemia with ring sideroblasts (MDS‐RARS), which is characterized by the anemia in clinic. However, the physiological roles of SF3B1 in erythropoiesis are poorly studied.

Aims:

To elucidate the biological functions of SF3B1 in specific stages of human erythropoiesis through precise temporal control of SF3B1 expression. To test the efficiency and safety of the new TET‐on lentiviral vector in differentiating cells.

Methods:

TET‐on lentiviral vector was constructed for conditional gene knockdown. Undifferentiated CD34+ cells were transduced with the Lentivirus and SF3B1 gene knockdown was induced by doxycycline in different differentiation stages across human erythropoiesis. The efficiency and safety of the TET‐on lentiviral vector were assessed by monitoring green fluorescent protein expression and erythroblasts differentiation, respectively. Knockdown of SF3B1 gene was checked by using qRT‐PCR and western blot analyses. The effects of SF3B1 ablation on progenitors were detected by colony forming assay and apoptosis was assessed by flow cytometry.

Results:

The TET‐on vector is efficient and safe for erythroblasts with no disturbance to the proliferation, differentiation, morphology and enucleation. Knockdown of SF3B1 in erythroblasts impairs erythroid colony forming and induced cell apoptosis. Interestingly, knockdown of SF3B1 shows temporal effects on erythropoiesis: in early stages, the deficiency of SF3B1 leads to significant cell apoptosis; however, it has no effect on cell growth at late stages of erythropoiesis.

Summary/Conclusion:

Our findings indicate that the TET‐on lentiviral vector is a powerful tool for precise temporal control of gene expression in differentiating cells, and SF3B1 is critical for the growth of early erythropoiesis.
PS1253 MAGNIFY: PHASE IIIB INTERIM ANALYSIS OF INDUCTION #R2 FOLLOWED BY MAINTENANCE IN PATIENTS WITH RELAPSED/REFRACTORY INDOLENT NON‐HODGKIN LYMPHOMA
Authors: Rummel M.J. , Andorsky D.J. , Coleman M. , Yacoub A. , Melear J.M. , Fanning S.R. , Kolibaba K.S. , Lansigan F. , Reynolds C. , Foon K. , Li J. , Llorente M. , Sharman J.
Published: June 2019

Background:

There is a lack of standard treatment approaches for patients with relapsed indolent non‐Hodgkin lymphoma (iNHL). Current study results with PI3K inhibitors have reported a median PFS of <1 y in the relapsed/refractory setting (R/R) for patients with iNHL. Lenalidomide, an immunomodulatory agent, enhances the activity of rituximab when combined into a regimen known as R2, which has recently reported a median PFS of 39.4 mo in patients with R/R iNHL patients from the phase III AUGMENT study (Leonard. ASH 2018:445).

Aims:

These analyses examine the interim primary endpoint of overall response rate (ORR; 1999 IWG) for induction R2 in efficacy‐evaluable patients receiving ≥ 1 treatment and who have available baseline and post‐baseline assessments.

Methods:

The multicenter, non‐registrational phase IIIb MAGNIFY trial in patients with R/R follicular lymphoma (FL) grade 1–3a and marginal zone lymphoma (MZL) was designed to determine the optimal duration of lenalidomide (NCT01996865). R2 treatment includes lenalidomide 20 mg/d, d1–21/28 plus rituximab 375 mg/m2/wk cycle 1 and q8wk cycles 3+ given for 12 cycles, and is followed by 1:1 randomization in patients with stable disease or better to continued R2 vs rituximab maintenance.

Results:

370 enrolled patients (80% FL grade 1–3a; 20% MZL) had a median age of 66 y, 83% stage III/IV disease, and a median of 2 prior therapies (95% prior rituximab‐containing). At a median 16.7 mo follow‐up, efficacy‐evaluable patients demonstrated a 73% ORR and 45% complete response (CR; Table). Similar efficacy results were shown for patients by histology. Overall, the median time to response (TTR) was 2.7 mo, median duration was response (DOR) was 36.8 mo, and median progression‐free survival (PFS) was 36.0 mo. According to their refractory status to rituximab at baseline, patients who were rituximab‐refractory and non‐refractory, respectively, had an ORR (CR) of 63% (40%) and 78% (47%), and median PFS of 18.1 mo and not reached. Of 370 patients who were randomized, 142 (38%) have entered the maintenance phase. The most common all‐grade adverse events were 48% fatigue, 40% neutropenia, 35% diarrhea, 30% nausea, and 29% constipation. Although the grade 3/4 adverse event neutropenia was 34%, all others were <6%.

Summary/Conclusion:

R2 therapy is an active treatment regimen in patients with R/R FL grade 1–3a and MZL, including patients refractory to rituximab, and with a tolerable safety profile.

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PS1258 CLONAL B‐CELL LYMPHOCYTOSIS OF MARGINAL ZONE ORIGIN (CBL‐MZ): CLINICAL SIGNIFICANCE OF ABSOLUTE CLONAL B CELL COUNTS
Authors: Kalpadakis C. , Pangalis G. , Konstantinou I. , Sachanas S. , Tsirkinidis P. , Moschogiannis M. , Yiakoumis X. , Siakantaris M. , Tsaftaridis P. , Iliakis T. , Befani M. , Dimopoulou M. , Asimakopoulos I. , Dimitrakopoulou A. , Butsikas G. , Korkolopoulou P. , Kontopidou F. , Koulieris E. , Pontikoglou C. , Ximeri M. , Psylaki M. , Roumelioti M. , Rontogiannis D. , Papadaki H. , Panagiotidis P. , Vassilakopoulos T. , Angelopoulou M.
Published: June 2019

Background:

CLL‐like MBL is divided into low and high count, with significant clinical and biological differences. No studies have been conducted so far in CBL‐MZ.

Aims:

In accordance to the proposed grouping of CLL‐like MBL, we aimed to investigate the clinical significance of such distinction in MZL‐like MBL.

Methods:

95 consecutive CBL‐MZ cases were analyzed, with any number of circulating CD5‐ CBL, no B‐symptoms, organomegaly, lymphadenopathy, cytopenias or any other features indicating a known lymphoproliferative disorder. Patients were grouped in 3 categories: A. low count (CBL≤500/μL), B. high count (CBL > 500/μL and ≤5000/μL) and C. frank lymphocytosis (CBL>5000/μL). Using this subdivision a comparison of several laboratory and disease evolution parameters was performed.

Results:

3/95 patients belonged to group A, 59 to group B and 33 to group C. The characteristics and outcome of the three groups are shown in table. Apart from WBC, ALC and CBL that differed significantly by definition, the only parameters that were statistically different between the three groups, were absolute neutrophil counts, CD11c expression, BM infiltration, and the frequency of evolution to SMZL. More specifically, the frequency of CD11c expression was highest in group C (68%) compared to group B (33%) and A (0%). Surprisingly, ANC were significantly higher with rising ALC. The percentage of BM infiltration differed significantly between the three groups and was highest in the lymphocytosis group (C); however, this difference was mainly due to the difference between group B and C. Notably, the three patients with low‐count MBL had BM infiltration between 30–40%, which was similar to the group C. There was a trend for a higher frequency for SMZL evolution in group C. Four out of 5 patients who evolved to SMZL belonged to the group C, whereas the remaining one patient had a low‐count MBL. At a median follow‐up time of 42 months, need of therapy, time to progression (TTP), time to treatment (TTT) and overall survival (OS) did not differ significantly between the three groups. Not CBL counts, but elevated LDH and BM infiltration≥50% were the only significant factors for TTT by multivariate analysis. Treatment due to cytopenias was more frequent in group B.

Summary/Conclusion:

CBL‐MZ patients have an excellent prognosis. The cut‐off of 5x109//L CBL does not seem to be the optimal threshold to distinguish prognostically different subgroups, with the exception of SMZL development. BM infiltration≥50% and elevated LDH are associated with shorter TTT.

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PS1260 EFFICACY OF MOGAMULIZUMAB IN PREVIOUSLY TREATED PATIENTS WITH LESS ADVANCED MYCOSIS FUNGOIDES: RESULTS FROM THE MAVORIC STUDY
Authors: Zinzani P.L. , Scarisbrick J. , Bagot M. , Fisher D.C. , Elmets C. , Duvic M. , Beylot‐Barry M. , Kim E.J. , Moriya J. , Leoni M. , Geskin L.J.
Published: June 2019

Background:

In the MAVORIC Phase 3 study, patients (pts) with previously treated mycosis fungoides (MF)/Sézary syndrome (SS) stage IB‐IVB who received mogamulizumab (MOGA) had significantly prolonged progression‐free survival and greater overall response rates (ORRs) compared to pts on vorinostat (VORI) (Kim et al. Lancet Oncol 2018). Less advanced MF (stage IB/IIA) is a chronic skin malignancy that can involve blood and lymph nodes and may require many lines of systemic therapy over the disease course.

Aims:

This post‐hoc analysis specifically examined efficacy and safety of the recently approved MOGA in stage IB/IIA MF pts.

Methods:

In MAVORIC, stage IB‐IVB MF/SS pts who were treated with ≥1 prior systemic therapy were randomized to MOGA or oral VORI. In the post‐hoc analysis, time to next treatment (TTNT) was defined as time to any therapy excluding topical steroids or focal radiation treatment. ORR was based on global composite response in 4 disease compartments – skin, blood, lymph nodes, and viscera – achieved at 2 consecutive visits at least 8 weeks apart. Individual compartment responses were also assessed.

Results:

A total of 85 pts with stage IB/IIA CTCL were included (MOGA, IB n = 15, IIA n = 21; VORI, IB n = 27, IIA n = 22). Overall, 24% (10/42) of IB pts and 28% (12/43) of IIA pts had received ≥6 prior therapies. Median TTNT with MOGA in IB pts was 11.5 months (mo) (95% CI, 1.4,16.0) compared to 3.1 mo (95% CI, 2.7, 5.3) with VORI; in IIA pts, median TTNT was 10.1 mo (95% CI, 5.5, 12.6) and 4.9 mo (95% CI, 2.4, 8.0), respectively. ORR in IB pts receiving MOGA and VORI was 20% (3/15) and 18.5% (5/27), respectively; ORR in IIA was 19% (4/21) and 0% (0/22), respectively. For stage IB and IIA, compartmental response rates with MOGA were – skin: 20% (3/15) and 38% (8/21), blood: 0% (0/2) and 75% (6/8), and lymph nodes: 0% (0/0) and 15% (3/20), respectively. Adverse events were generally manageable and consistent with the ITT population.

Summary/Conclusion:

Though MAVORIC was not powered to determine treatment effect by disease stage, this post‐hoc analysis of TTNT, ORR, and compartmental response in stage IB/IIA demonstrates meaningful clinical benefit with MOGA in previously treated, less advanced MF pts.
PS1275 INVASIVE ASPERGILLOSIS CAUSED BY ”RARE“ PATHOGENS: CLINICAL REGISTRY DATA ANALYSIS
Authors: Shadrivova O. , Ryabinin I. , Desyatik E. , Borzova Y. , Volkova A. , Popova M. , Bogomolova T. , Zubarovskaya L. , Afanasyev B. , Vasilyeva N. , Klimko N.
Published: June 2019

Background:

Publications describing invasive aspergillosis (IA) caused by “rare” pathogens are limited. Species identification of the pathogen is necessary for the selection of antifungal therapy, as some Aspergillus spp. may be resistant to antifungal drugs.

Aims:

Analysis clinical registry data of patients with IA caused by “rare” pathogens

Methods:

Retrospective analysis of patients with IA caused by “rare” pathogens in 1998–2019 yy. For the IA diagnosis EORTC / MSD, 2008 criteria were used. In accordance with the European guidelines, DNA sequencing and MALDI‐TOF were used to identify of the “rare” Aspergillus spp.

Results:

In our registry we included 800 patients with IA. In 227 patients Aspergillus spp. were isolated. The “rare” pathogens were detected in 18 (8%), and these patients were included in group I; age varied from 5 to 67 years, median – 40.5,males – 50%. The control group consisted 209 patients with other Aspergillus spp. (A. fumigatus,A. niger and A. flavus), from 1 to 99 years old, median ‐ 47, males – 53%. In both groups IA predominantly occurs in patients with hematologic malignancies (73% vs 76%): acute leukemia – 27% vs 33%, lymphoma – 22% vs 27%, multiple myeloma 12% vs 6%, chronic leukemia 6% in each group, other hematological diseases – 6% vs 4%. We identified, IA caused by ”rare“ pathogens more often developed in children(22% vs 11%, p < 0.05).

In addition to standard risk factors, in patients with ”rare“ pathogens more often was detected lymphocytopenia 67% vs 55%, with duration 21 vs 14 days, p < 0.05, less frequent was noted fever (46% vs 78%, p <  0.05), but significantly more lung damage accompanied by hemoptysis (17% vs 10%, p <  0.05). “Rare” pathogens were A. ustus – 38%, A. nidulans – 22%, A. calidoustus – 8%,A. versicolor– 8%,A.glaucus – 8%,A. candidus – 8%, andA. sydowii – 8%. In controlgroup etiological agents were A. fumigatus – 52%,A. niger – 31%, A. flavus– 17%. Two or more species of Aspergillus were isolated in 44% vs 9%, p < 0.05. Antifungal therapy was used in 100% vs 97% of patients. Twelve weeks overall survival rate was 82% vs 81%. In the group with “rare” pathogens more frequently observed relapse of IA – 33% vs 12%, p <0.05.

Summary/Conclusion:

Patients with “rare” pathogens account for 8% of patients with isolated Aspergillus spp. cultures. IA caused by ”rare“ pathogens, more often occurs in children – 22%. The features of IA caused by “rare” pathogens are: long‐term lymphocytopenia (67%, median ‐ 21 days), combination of two or more pathogens – 44%, high relapse rate – 33%. Survival of patients with “rare” pathogens does not differ from the total cohort of patients – 82%.
PS1286 INVASIVE YEAST INFECTIONS IN HEMATOLOGICAL PATIENTS AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Popova M. , Rogacheva Y. , Volkova A. , Markova I. , Frolova A. , Shvetcov A. , Nikolaev I. , Goloshchapov O. , Bykova T. , Paina O. , Gevorgian A. , Darskaya E. , Vladovskaya M. , Bondarenko S. , Moiseev I. , Baykov V. , Zubarovskaya L. , Klimko N. , Afanasyev B.
Published: June 2019

Background:

Invasive yeast infection is rare invasive fungal disease but associated with high mortality rate in hematological patients. Data on Invasive yeast infection in hematopoietic stem cell transplantation (HSCT) recipients are limited.

Aims:

The aim of our study was to estimate epidemiology of invasive yeast infections in large HSCT recipients’ cohort for the 10‐year period transplant activity in CIC725.

Methods:

Between 2008 and 2017 2430 stem cell transplantation have been performed in CIC 725: 1647 allogeneic HSCT and 783 autologous HSCT. A retrospective study included 30 cases of invasive yeast infections in patients with hematological malignances and non‐malignant hematological diseases after HSCT. EORTC/MSG 2008 criteria were used for the diagnosis of proven yeast infections as well as to evaluate response to therapy.

Results:

Incidence of invasive yeast infections for the 10‐year period of high transplant activity was 1,2%: 1,4% in allo‐HSCT recipients (n = 23), 0,9% – auto‐HSCT (n = 7) predominantly in patients with acute leukemia – 67% (n = 20). The median age was 10 y.o. (range, 1 month‐59 years). In study population allo‐HSCT from unrelated donor was performed in 50% (n = 15), haplo‐HSCT in 27% (n = 8) and auto‐HSCT in 23% (n = 7). In study cohort 30% of patients had no complete remission at the moment of HSCT. As a primary antifungal prophylaxis was used: fluconazole – 37% (n = 11), echinocandins – 13% (n = 4), without prophylaxis – 23% (n = 7); as a secondary prophylaxis – voriconazole in 27% (n = 8). The median day of onset of invasive yeast infections after allo‐HSCT was 109 days (3–1337), auto‐HSCT – 20 days (8–33). The etiology of invasive yeast infections was: Candida spp. – 87% (n = 26), Malassezia furfur – 7% (n = 2), Trichosporon asahii – 3% (n = 1), Cryptococcus spp. – 3% (n = 1). Febrile fever was the main clinical symptom and septic syndrome developed in 60% of cases. OS at 30 days from diagnosis of invasive yeast infection was 63%. The central venous catheter removal was the only factor significantly improved OS at 30 days after invasive yeast infection diagnosis (91% vs 17%, p = 0,001).

Summary/Conclusion:

Incidence of invasive yeast infections for the 10 years of observation was 1,2%: 1,4% in allo‐HSCT recipients, 0,9% – auto‐HSCT. The main etiology was Candida spp. (87%). Overall survival at 30 days from the diagnosis of invasive yeast infections was 60%. Removing of central venous catheter improved overall survival in hematological patients after HSCT with invasive yeast infections.
PS1290 HEPARIN‐ANALOGUE SEVUPARIN INHIBITS STREPTOCOCCUS‐INDUCED VASCULAR HYPERPERMEABILITY THROUGH NEUTRALIZING NEUTROPHIL‐DERIVED PROTEINS
Authors: Wahlgren M. , Rasmuson J. , Kenne E. , Soehnlein O. , Lindbom L.
Published: June 2019

Background:

Acute lung injury (ALI) and respiratory distress can develop as a consequence of sepsis with pathogens such as Group A streptococcus (GAS) including S. pyogenes. In the pathogenesis of sepsis‐associated ALI, plasma exudation and leukocyte accumulation in the lungs are central events, and endothelial barrier disruption brought on by degranulation of neutrophil‐derived proteins is considered a causative factor. Heparin and heparin derivatives have been suggested as novel therapeutics in sepsis on the basis of their pleiotropic anti‐inflammatory effects.

Aims:

Here, we study wheter sevuparin, a heparinoid wihich lacks anticoagulant activity, affects neutrophil‐induced lung plasma leakage.

Methods:

A murine model of systemic inflammation evoked by heat‐killed GAS and furthermore, we utilized human neutrophils and endothelial cell monolayers

Results:

We demonstrate that sevuparin inhibits hkGAS‐induced endothelial barrier disruption by neutralizing the activity of neutrophil‐derived proteins. By mass spectrometry of neutrophil secretion we identify candidate proteins, including serprocidins, S100 proteins and histone H4, that interact with sevuparin and that are responsible for the disruptive effect on endothelial integrity.

Summary/Conclusion:

Collectively, our results corroborate the role of neutrophil‐derived proteins in vascular hyperpermeability caused by Group A streptococci, and suggest sevuparin as a potential therapeutic in acute neutrophilic inflammation.
PS1300 A NURSE LED IRON INFUSION CLINIC REDUCES POTENTIAL PATIENT HARM AND IMPROVES HOSPITAL EFFICIENCY
Authors: Newman L. , Wright T.
Published: June 2019

Background:

The introduction of a rapid iron infusion protocol (ferric carboxymaltose) whilst more convenient and safe for patients has the potential to change the management of iron deficiency anaemia (IDA) away from best practice guidelines. Latrobe Regional Hospital (LRH) deliver all outpatient intravenous (IV) iron infusions through their chemotherapy day unit (CDU), providing an opportunity to study the total prescribing practices in a busy rural referral centre.

Aims:

To assess the appropriateness of intravenous iron prescribing in a regional setting and implement service improvement projects where deviations from best practice were identified.

Methods:

Baseline data of all IV iron infusions was collected from May 2017 to January 2018 (PRE phase 9 months). From February to October 2018 (POST‐phase 9 months), referrals from primary care physicians requesting an iron infusion were assessed by a haematology clinical nurse consultant (CNC) iron infusion clinic with physician supervision. All internal medicine specialist requests for iron infusions were coordinated by the haematology CNC. Iron infusion and prescribing rates were summarised for three groups, physician, local medical officer (LMO) and obstetrics and gynaecology (O & G). All requests for iron infusions were assessed according to best practice guidelines.

Results:

Table one summarises the total 311 iron infusions delivered over the 9‐month pre‐phase data collection period. The physician group referred an older population of both males and females. The LMO referral group were predominantly female.

Figure one shows the average monthly IV iron infusions delivered for the entire collection period and as per each referral group.

There was a significant reduction in the average monthly IV iron infusions from 38 to 23. Monthly infusions delivered following referrals from the LMO group reduced significantly from 17 to 6. Whilst referrals from the physician group increased and O & G group decreased, these were not significant.

Summary/Conclusion:

The development of an iron infusion clinic led by a haematology CNC provides a safe evidenced based assessment of patient referrals. This model significantly reduced the rate of iron infusions in our regional hospital, allowing more efficient use of the expert outpatient infusion centre services and reducing potential harm related to an inappropriate therapy.

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PS1358 POTENT ANTI‐MYELOMA EFFICACY OF DENDRITIC CELL THERAPY IN COMBINATION WITH POMALIDOMIDE AND PROGRAMMED DEATH‐LIGAND 1 BLOCKADE IN A PRECLINICAL MODEL OF MULTIPLE MYELOMA
Authors: Jung S.‐H. , Chu T.‐H. , Vo M.‐C. , Park H.‐S. , Lakshmi T.J. , Ahn S.‐Y. , Kim H.‐J. , Lee J.‐J.
Published: June 2019

Background:

Dendritic cell (DC)‐based vaccines are recognized as a promising immunotherapeutic strategy against cancer, and various combination approaches have been developed to enhance DC function by modulating immune responses and tumor microenvironment.

Aims:

In this study, we investigated the efficacy of DC vaccination in combination with pomalidomide and programmed death ligand‐1 (PD‐L1) blockade in a murine model of multiple myeloma (MM).

Methods:

MOPC‐315 cell lines were injected subcutaneously to establish MM bearing mice. Four test groups were used to mimic clinical protocol: (1) PBS control, (2) DCs + pomalidomide/dexamethasone, (3) Pomalidomide/dexamethasone + PD‐L1 blockade, and (4) DCs + pomalidomide/dexamethasone + PD‐L1 blockade.

Results:

The combination of DCs + pomalidomide with dexamethasone + PD‐L1 blockade inhibited more strongly tumor growth and prolonged survival of treated mice compared to the other groups. This effect was associated with a significant reduction in immune suppressor cells, such as myeloid‐derived suppressor cells, regulatory T cells, and M2 macrophages, and level of immunosuppressive factors, such as vascular endothelial growth factor, transforming growth factor‐β, and interleukin‐10, and with the significant induction of immune effector cells, such as CD4+ and CD8+ T cells, memory T cells, natural killer (NK) cells, and M1 macrophages, in the spleen and tumor microenvironment. Functional activities of cytotoxic T lymphocytes and NK cells in spleen were also enhanced by the combination of DCs + pomalidomide with dexamethasone + PD‐L1 blockade.

Summary/Conclusion:

The collective findings in the murine MM model suggest that DC vaccination combined with pomalidomide and PD‐L1 blockade synergistically enhance antitumor immunity through two‐way mechanism, which inhibits immunosuppressive cells while activating effector cells with superior polarization of the Th1/Th2 balance in favor of the tumor immune response.