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BackgroundAngioimmunoblastic T-cell lymphoma (AITL) is known for its unfavorable survival prognosis. Chidamide has shown efficacy in relapsed/refractory AITL, but its efficacy in newly diagnosed AITL is uncertainObjectiveThis retrospective research aimed to evaluate the effectiveness and safety of chidamide when used with doxorubicin, cyclophosphamide, prednisone, and vincristine (CHOP) in comparison to CHOP by itself for individuals newly diagnosed with AITL, and to examine the impact of transplantation.MethodThis was an analysis that compared outcomes among patients who received chidamide + CHOP on a clinical trial vs. historical controls who received CHOP alone, enrolling a total of sixty-six treatment-naive AITL patients between April 2014 and November 2022. Among them, thirty-three received chidamide in addition to CHOP (chidamide group), while thirty-three received CHOP alone (control group). The clinical characteristics were balanced between the two groups. All patients were scheduled to undergo up to six courses of treatment before transplantation.ResultsThe chidamide group had a significantly longer median overall survival (OS) compared to the control group, with a median OS that was not reached, as opposed to 20 months in the control group (p = 0.002). In the control group, the median progression-free survival (PFS) was 11 months, while in the chidamide group, it was 22 months (p = 0.080). In the high-risk group (IPI ≥ 3), the chidamide group demonstrated notably superior complete response (CR) and overall response rate (ORR) compared to the control cohort (p = 0.002, p = 0.034). The PFS and OS in the chidamide group were not reached, and there were significant differences compared to the control group (p = 0.007, p = 0.003). The median OS of the transplanted group was longer than the non-transplanted group (p = 0.004). On multivariate analysis, chidamide group reduced the hazards of death in the total cohort.ConclusionAs the study was non-random and retrospective, Chidamide combined with chemotherapy should be tested in randomized trials given its potential to improve prognosis in treatment-naive AITL patients. Furthermore, autologous hematopoietic stem cell transplantation (auto-HSCT) has demonstrated enhanced overall survival in individuals with AITL.Clinical trial registrationhttps://clinicaltrials.gov/, NCT03268889

Abstract HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2–76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9–87.5%) and 75.4% (95% CI: 68.9–82.6%)( HR: 0.75, 95% CI 0.47–1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4–84.6%) and 73.0% (95% CI: 66.3–80.3%) (HR: 0.84, 95% CI 0.54–1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

Abstract From October 2017 to June 2022, we retrospectively report outcomes of R/R DLBCL patients with failure of CAR-T therapy, then receiving allo-HSCT. Among 10 patients, 5 were males and 5 females, with a median age of 43.5 (27–52) years. All patients were diagnosed refractory/relapsed diffuse large B cell lymphoma. The median time from CAR-T treatment to transplantation was 84.5 (31–370) days. The median follow-up was 21 (3–69) months. 5/10 patients attained CR and 1/10 patient attained PR during the follow up. The objective response rate (ORR) was 60%. The 1-year overall survival (OS) and progression-free survival (PFS) were 70% and 40%, respectively. At the time of the analysis, 6 patients were still living. During the follow up, four patients have died and the causes were disease relapses and progressions (2 patients), acute renal failure (1 patient), severe pulmonary infection (1 patient). Non-relapse was 20.0%.

Abstract CD19 chimeric antigen receptor (CAR) T-cell therapy has shown great success against B-cell acute lymphoblastic leukemia (B-ALL). Tandem and sequential CD19/CD22 dual-target CAR T-cell therapies have been developed to reduce the possibility of CD19-negative relapse; however, the superior strategy is still uncertain. This study screened 219 patients with relapsed/refractory B-ALL who were enrolled in clinical trials of either CD19 (NCT03919240) or CD19/CD22 CAR T-cell therapy (NCT03614858). The complete remission (CR) rates in the single CD19, tandem CD19/CD22, and sequential CD19/CD22 groups were 83.0% (122/147), 98.0% (50/51), and 95.2% (20/21), respectively (single CD19 vs. tandem CD19/CD22, P = 0.006). Patients with high-risk factors achieved a higher rate of CR in the tandem CD19/CD22 group than in the single CD19 group (100.0% vs. 82.4%, P = 0.017). Tandem CD19/CD22 CAR T-cell therapy was one of the significant favorable factors in the multivariate analysis of the CR rate. The incidence of adverse events was similar among the three groups. Multivariable analysis in CR patients showed that a low frequency of relapse, a low tumor burden, minimal residual disease-negative CR and bridging to transplantation were independently associated with better leukemia-free survival. Our findings suggested that tandem CD19/CD22 CAR T-cell therapy obtains a better response than CD19 CAR T-cell therapy and a similar response to sequential CD19/CD22 CAR T-cell therapy.

Chimeric antigen receptor T-cell therapy (CAR-T) has been widely applied in the clinical practice of relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) due to its promising effects. Hyperprogressive disease (HPD) has gained attention for rapid tumor progression and has become a therapeutic and prognostic challenge. Here, we present a patient who had suffered from several recurrences previously and controlled well with a very small tumor lesion left was infused with CD19/CD22 bispecific CAR-T, with no immune effector cell-associated neurotoxicity syndrome, or cytokine release syndrome observed. However, rapid deterioration, subsequent imaging examination, circulating tumor DNA, and serum biomarkers detection identified HPD. The patient did not respond to salvage treatment and died 40 days after infusion. To our knowledge, only one case of HPD in DLBCL after CAR-T therapy has been reported. This fatal case alarmed the risk of HPD and the ctDNA profile monitoring we used was performed as a non-invasive method to diagnose HPD, providing far-reaching practical instruction for CAR-T therapy.

Objectives The aim of this retrospective study was to evaluate the safety and efficacy of SEAM regimen followed by auto-SCT in lymphoma.Patients and methods We retrospectively reviewed the records of patients with lymphoma who underwent auto-SCT with SEAM conditioning regimen from January 2010 to June 2018 at our centre. In total, 97 patients were analysed.Results The median time to neutrophil engraftment and platelet engraftment was 9.5 days (range, 7–15 days) and 12 days (range, 7–25 days), respectively. Grade 3–4 nausea/vomiting, mucositis and diarrhoea were observed in 21.6%, 36.1%, and 11.3% of patients, respectively. Treatment-related mortality at 100 days occurred in 2 patients (2.1%). After a median follow-up time of 53.9 months, the 3-year incidence of disease relapse or progression was 34%. The estimated progression-free survival and overall survival at 3 years were 62% and 75%, respectively. Compared with previous studies using BEAM as the conditioning regimen, this study shows that the SEAM regimen has a comparable efficacy and safety profile.Conclusions The SEAM regimen is feasible and might be an ideal alternative to BEAM regimen for lymphoma auto-SCT.

Background: The role of body mass index (BMI) in the treatment outcomes of lymphoma patients is controversial. While investigating the efficacy of ABVD-like regimen in Hodgkin lymphoma (HL) patients, we observed that obese patients had poor responses. To better understand this clinical phenomenon, we evaluated the effect of BMI on responses to ABVD-like chemotherapy in HL patients.Methods: This retrospective cohort study evaluated the clinical outcomes of all 67 patients with confirmed HL who were treated at the First Affiliated Hospital of Soochow University from November 2016 to March 2023 with an ABVD-like regimen as first-line chemotherapy. Baseline patient characteristics and clinical outcomes were compared across different BMI categories. The primary end-point was the overall response rate defined as the proportion of the HL patients who achieved complete response or partial response. The additional end-points included progression-free survival and overall survival.Results: The median age of the HL patients was 31 years old. Of the patients, 10.4% were obese, and 17.9% patients were overweight. Interim and end-term response evaluations revealed overall response rates of 98.5% and 83.6%, respectively. The proportion of patients with potential poor prognostic factors (IPS risk factors) did not differ significantly in the responders versus non-responders. However, non-responders had a higher average BMI when compared with responders (p = 0.002). Poor overall response rates in higher BMI patients indeed manifested with shorter progression free survival (p = 0.013). The minimum relative dose of the ABVD-like regimen in the overweight and obese groups was significantly lower than in the normal weight group (p < 0.001).Conclusion: Our analyses show that >80% of newly-diagnosed HL patients responded to the ABVD-like regimen. We find that being obese or overweight at the time of diagnosis correlated with a poorer overall response rate and that BMI was an independent risk factor in HL patients treated with the ABVD-like regimen. Lower doses of ABVD-like regimen contributed to the discrepant findings of responses in the high BMI groups. These findings indicate that newly-diagnosed, obese HL patients receiving an ABVD-like regimen require personalized treatment.

BackgroundChimeric antigen receptor T cell (CAR-T) therapy is an effective salvage treatment in relapsed or refractory(r/r) diffuse large B-cell lymphoma (DLBCL), but the impact of hepatitis B virus (HBV) infection has not been studied.Methods and resultsHere, 51 patients with r/r DLBCL receiving CAR-T therapy were enrolled and analyzed at the First Affiliated Hospital of Soochow University. The overall response rate and the complete remission rate (CR) of CAR-T therapy were 74.5% and 39.2%, respectively. With a median follow-up of 21.1 months after CAR-T, the probabilities of overall survival (OS) and progression-free survival (PFS) at 36 months were 43.4% and 28.7%, respectively. These patients were divided into three cohorts including chronic HBV infection group (n=6), resolved HBV infection group (n=25) and non-HBV infection group (n=20). Bone marrow involvement was significantly higher in the HBV infection group(P

Abstract Persistence of CAR-T cell function is associated with relapse rate after CAR-T therapy, while co-stimulatory agents are highly concerned with the persistence of CAR-T cells. In this study, we designed and constructed a series of BCMA-targeting second-generation CAR constructs containing CD28, 41BB, and OX40 molecules, respectively, to identify the costimulatory domains most favorable for persistence. The results of routine in vitro studies showed that OX40-CAR-T and 41BB-CAR-T had similar antitumor effects and were superior to CD28-CAR-T in terms of proliferation and cytotoxicity. Although difficult to distinguish by conventional functional assays, OX40-CAR-T cells exhibited greater proliferation and enhanced immune memory than 41BB-CAR-T cells with the repeated stimulation assay by BCMA-expressing target cells. In vivo studies further demonstrated that OX40-CAR-T cells had stronger proliferative activity than 41BB-CAR-T cells, which was highly consistent with the in vitro antitumor activity and proliferation results. Our study provides for the first time a scientific basis for designing OX40-CAR-T cell therapy to improve relapse in patients with MM after CAR-T treatment.

Chimeric antigen receptor T cell (CAR-T) therapy has emerged as highly effective in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but only about 40% patients have achieved sustained responses. Here, we conducted a phase II clinical trial testing efficacy and toxicities of CAR-T therapy in R/R non-Hodgkin’s lymphoma patients (NCT03196830). Among enrolled patients, 33 R/R DLBCL patients pretreated with DFC (decitabine, fludarabine plus cyclophosphamide) lymphodepletion chemotherapy and infused with tandem CD19-CD22 based CAR-T cells were drawn out for efficacy and toxicities of CAR-T therapy evaluation. With a median follow-up of 10.9(0.6-29.0) months, the best overall response and complete remission (CR) rates were 90.9% and 63.6%, respectively. The median progression-free survival (PFS) was 10.2 months and overall survival (OS) was undefined. The 2-year OS and PFS rates were 54.3% and 47.2%, respectively. No severe grade 4 cytokine release syndrome (CRS) was observed and grade 3 CRS was observed in only 7 patients; 3 patients developed mild immune effect or cell-associated neurotoxic syndrome. All toxicities were transient and reversible and no CAR-T-related mortality. Further subgroup analysis showed that achieving CR was an independent prognostic factor associated with favorable PFS and OS. The 2-year OS and PFS for patients who achieved CR within 3 months (undefined versus undefined P=0.021 and undefined versus undefined P=0.036) or during the follow-up period were significantly longer than those who did not (undefined versus 4.6 months P < 0.0001 and undefined versus 2.0months P

The purpose of this study in severe aplastic anemia (SAA) patients was to compare the feasibility and efficacy of haploidentical hematological stem cell transplantation combined with a single unrelated cord blood (UCB) infusion (Haplo-cord-HSCT) or haplo-identical HSCT (Haplo-HSCT) alone. The five-year graft-versus-host disease (GVHD)-free or failure-free survival (GFFS) was similar between the two groups (72.4 ± 3.4% vs. 65.4 ± 5.2%, P = 0.178); however, the five-year overall survival (OS) was more favorable in the Haplo-cord-HSCT group than that in the Haplo-HSCT group (84.0 ± 2.8% vs. 72.6 ± 4.9%, P = 0.022), as was transplantation-related mortality (16.4% vs. 27.4%, P = 0.039). Multivariate analysis showed that Haplo-cord HSCT was the only independent determinant of increased OS (P = 0.013). Explorative subgroup analysis showed that only an Human leukocyte antigen-A (HLA-A) allele match between UCB and the recipient was a beneficial factor for GFFS in the Haplo-cord-HSCT group (P = 0.011). In the haplo-cord with an HLA-A match (n = 139) or mismatch (n = 32) or Haplo-HSCT groups, a haplo-cord HLA-A allele match was associated with lower I–IV and III–IV acute GVHD. The haplo-cord with an HLA-A match subgroup also had higher five-year OS than the Haplo-HSCT group (85.4 ± 3.0% vs. 72.6 ± 4.9%, P = 0.013), and higher five-year GFFS than the Haplo-cord HLA-A allele mismatch subgroup (76.2 ± 3.6% vs. 56.3 ± 8.8%, P = 0.011). These findings suggest that the coinfusion of a single UCB potentially improves survival of Haplo-HSCT in SAA patients and that an HLA-A allele-matched UCB is the preferred option.

BackgroundHaploidentical donor hematopoietic cell transplantation (haplo-HCT) has become a preferred option for patients without HLA-matched donors, but it increases the risk of viral reactivations. Epstein–Barr virus (EBV) and cytomegalovirus (CMV) are common viruses post-HCT, but limited data have been reported in the setting of haplo-HCT.MethodsWe conducted a retrospective study enrolling acute leukemia patients who received haplo-HCT with myeloablative conditioning regimen employing ATG in our center from July 2014 to July 2017. All the patients enrolled were EBV-IgM and EBV-DNA negative but EBV-IgG positive, and so were their donors. The same went for CMV as well.ResultsIn total, 602 patients were recruited consisting of 331 with acute myeloid leukemia (AML) and 271 with acute lymphoblastic leukemia (ALL). One-year cumulative incidences of EBV (22.9% ± 2.4% vs. 27.4% ± 2.8%, P = 0.169) and CMV (24.7% ± 2.4% vs. 29.4% ± 2.8%, P = 0.190) reactivation were comparable between AML and ALL. EBV and CMV were independent risk factors for each other. In the AML group, male recipients [HR = 1.275, 95% CI (1.001–1.624), P = 0.049] and acute graft-versus-host disease [HR = 1.592, 95% CI (1.001–2.533), P = 0.049] were independent risk factors for EBV reactivation and CMV reactivation, respectively. CMV rather than EBV reactivation was related to a trend of worsened treatment-related mortality (TRM) (15.6% ± 0.1% vs. 10.2% ± 0.0%, P = 0.067) and progression-free survival (PFS) (60.6% ± 4.1% vs. 70.3% ± 2.3%, P = 0.073), while significant impacts were revealed only in the subgroup analysis. CMV reactivation resulted in a remarkable inferior 2-year overall survival (OS) (64.2% ± 5.7% vs. 77.6% ± 3.2%, P = 0.038) and PFS (55.0% ± 5.9% vs. 71.9% ± 3.4%, P = 0.042) in ALL patients. On the other hand, in the EBV+/CMV− subgroup, relapse was lower in ALL patients (8.2% ± 0.2% vs. 32.4% ± 0.8%, P = 0.010) compared with AML patients, which led to a superior 2-year OS (82.0% ± 6.2% vs. 60.3% ± 8.8%, P = 0.016) and PFS (74.5% ± 7.0% vs. 57.5% ± 8.4%, P = 0.036).ConclusionWe concluded that EBV and CMV reactivations were frequent in acute leukemia patients after haplo-HCT, with possibly distinctive risk factors from HLA-matched HCT. There could be a potential interaction between EBV and CMV, but impacts on transplant outcomes remained complex.

Background/AimsChimeric antigen receptor (CAR) T cells for refractory or relapsed (r/r) B-cell acute lymphoblastic leukemia (ALL) patients have shown promising clinical effectiveness. However, the factors impacting the clinical response of CAR-T therapy have not been fully elucidated. We here aimed to identify the independent factors of CAR-T treatment response and construct the models for predicting the complete remission (CR) and minimal residual disease (MRD)-negative CR in r/r B-ALL patients after CAR-T cell infusion.MethodsUnivariate and multivariate logistic regression analyses were conducted to identify the independent factors of CR and MRD-negative CR. The predictive models for the probability of remission were constructed based on the identified independent factors. Discrimination and calibration of the established models were assessed by receiver operating characteristic (ROC) curves and calibration plots, respectively. The predictive models were further integrated and validated in the internal series. Moreover, the prognostic value of the integration risk model was also confirmed.ResultsThe predictive model for CR was formulated by the number of white blood cells (WBC), central neural system (CNS) leukemia, TP53 mutation, bone marrow blasts, and CAR-T cell generation while the model for MRD-negative CR was formulated by disease status, bone marrow blasts, and infusion strategy. The ROC curves and calibration plots of the two models displayed great discrimination and calibration ability. Patients and infusions were divided into different risk groups according to the integration model. High-risk groups showed significant lower CR and MRD-negative CR rates in both the training and validation sets (p < 0.01). Furthermore, low-risk patients exhibited improved overall survival (OS) (log-rank p < 0.01), higher 6-month event-free survival (EFS) rate (p < 0.01), and lower relapse rate after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T cell infusion (p = 0.06).ConclusionsWe have established predictive models for treatment response estimation of CAR-T therapy. Our models also provided new clinical insights for the accurate diagnosis and targeted treatment of r/r B-ALL.

Abstract Rituximab in combination with chemotherapy has shown efficacy in patients with diffuse large B-cell lymphoma (DLBCL) for more than 15 years. HLX01 was developed as the rituximab biosimilar following a stepwise approach to demonstrate biosimilarity in analytical, pre-clinical, and clinical investigations to reference rituximab. With demonstrated pharmacokinetic similarity, a phase 3 multi-center, randomized, parallel, double-blind study (HLX01-NHL03) was subsequently conducted to compare efficacy and safety between HLX01 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (H-CHOP) and reference rituximab plus CHOP (R-CHOP) in a total of 407 treatment-naïve, CD20-positive DLBCL patients aged 18–80 years. The primary efficacy endpoint was best overall response rate (ORR) within six cycles of treatment in the per-protocol set (PPS). Secondary endpoints included 1-year efficacy outcomes, safety, and immunogenicity profile. The results showed difference in ORRs [H-CHOP 94.1%; R-CHOP 92.8%] between two treatment groups was 1.4% (95% confidence interval [CI], − 3.59 to 6.32, p = 0.608) which falls within the pre-defined equivalence margin of ± 12%. The safety profile was comparable between the treatment groups, with a similar overall incidence of treatment-emergent adverse events (H-CHOP 99.5%, R-CHOP 99.0%, p = 1.000) and serious adverse events (H-CHOP 34.0%, R-CHOP 32.5%, p = 0.752). This study established bioequivalence in efficacy and safety between HLX01 and reference rituximab. The trial was registered at http://www.chinadrugtrials.org.cn on 26 August 2015 [#CTR20150583].

We retrospectively compared the outcomes and health-related quality of life (HRQoL) of severe aplastic anemia (SAA) patients who received haploidentical hematopoietic stem cell transplantation with a single unrelated cord blood unit (Haplo-cord HSCT) (n = 180) or matched related donor (MRD)-HSCT (n = 128). After propensity score matching, we were able to match 88 patients in each group and to compare the outcomes between the two matched-pair groups. Haplo-cord recipients exhibited a longer median days for neutrophil engraftment (12 vs 11, P = 0.001) and for platelet engraftment (15 vs 13, P = 0.003). Haplo-cord recipients a high cumulative incidence of grades II–IV acute graft-versus-host disease (GVHD) (29.8 vs 14.0%, P = 0.006), while similar III–IV acute GVHD, total chronic GVHD, and moderate to severe chronic GVHD at four-year (all P < 0.05). Among the Haplo-cord HSCT and MRD-HSCT groups, the four-year GVHD-free/failure-free survival rates were 73.5% and 66.9% (P = 0.388) respectively, and the overall survival rates were 81.5% and 77.2% (P = 0.484), respectively. Similar comparable results also were observed between the corresponding first-line, older or younger than 40 years old subgroups. The Haplo-cord HSCT group exhibited higher scores in the physical component summary, physical functioning, general health and social functioning than the MRD-HSCT group (all P < 0.05). In the multivariate analysis, young age and Haplo-cord HSCT were favorable factors for HRQoL, while moderate to severe cGVHD was associated with lower HRQoL. These results suggest that for SAA patients, Haplo-cord HSCT could achieve at least comparable efficacy and HRQoL to MRD-HSCT.

Philadelphia chromosome positive (Ph+) in T-lineage acute lymphoproliferative tumors is a rare event in both children and adults. In particular, it has not been reported in T-cell lymphoblastic lymphoma(T-LBL) yet. Here, we describe a patient with Ph+ T-LBL for both cytogenetic abnormality and BCR-ABL1 fusion transcript. Moreover, we review the published cases of Ph+ T-cell acute lymphoblastic leukemia (T-ALL) in the literature and summarize their clinical characteristics, management, and prognosis.

Background: Blood-based biomarker such as circulating tumor DNA (ctDNA) has emerged as a promising tool for assessment of response to immunotherapy in solid tumors; But in hematological malignances, evidences are still lacking to support its clinical utility. In current study the feasibility of ctDNA for prediction and monitoring of response to anti-PD-1 therapy in Chinese patients with relapsed or refractory classical Hodgkin lymphoma (r/r cHL) was assessed. Methods: A total of 192 plasma samples from 75 patients with r/r cHL were collected at baseline and upon therapeutic evaluation. ctDNA were sequenced by targeting panels capturing frequently mutated genes in cHL and other hematological malignancies and then quantified. Analysis on: 1) Gene mutation profile and association of the gene mutations with progression-free survival; 2) Association of pre- and post-treatment ctDNA variant allelic frequencies with clinical outcome; (3) Correlation of the mutated genes with treatment resistance; were performed. Findings: Somatic mutations were detected in 50 out of 61 patients by ctDNA genotyping. The mutations of CHD8 was significantly higher in patients with PFS ≥ 12 months. Baseline ctDNA was significantly higher in responders and a decrease of ctDNA ≥ 40% from baseline indicated superior clinical outcome. Strong agreement between ctDNA dynamic and radiographic response change during therapy was observed in majority of the patients. Furthermore, the mutations of B2M, TNFRSF14 and KDM2B were found to be associated with acquired resistance. Interpretation: ctDNA could be an informative biomarker for anti-PD-1 immunotherapy in r/r cHL. Funding: This work was supported by Innovent Biologics, Eli Lilly and Companyhttps://doi.org/10.13039/501100002852, China National New Drug Innovation Program (2014ZX09201041-001 and 2017ZX09304015), Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001) and National Key Scientific Program Precision Medicine Research Fund of China (2017YFC0909801). The funders had no role in study design, data collection, data analysis, interpretation or writing. Keywords: Circulating tumor DNA, Immunotherapy, anti-PD-1, Biomarker, Classical hodgkin lymphoma, Sintilimab

Abstract The efficacy and safety of chidamide, a new subtype-selective histone deacetylase (HDAC) inhibitor, have been demonstrated in a pivotal phase II clinical trial, and chidamide has been approved by the China Food and Drug Administration (CFDA) as a treatment for relapsed or refractory peripheral T cell lymphoma (PTCL). This study sought to further evaluate the real-world utilization of chidamide in 383 relapsed or refractory PTCL patients from April 2015 to February 2016 in mainland China. For patients receiving chidamide monotherapy (n = 256), the overall response rate (ORR) and disease control rate (DCR) were 39.06 and 64.45%, respectively. The ORR and DCR were 51.18 and 74.02%, respectively, for patients receiving chidamide combined with chemotherapy (n = 127). For patients receiving chidamide monotherapy and chidamide combined with chemotherapy, the median progression-free survival (PFS) was 129 (95% CI 82 to 194) days for the monotherapy group and 152 (95% CI 93 to 201) days for the combined therapy group (P = 0.3266). Most adverse events (AEs) were of grade 1 to 2. AEs of grade 3 or higher that occurred in ≥5% of patients receiving chidamide monotherapy included thrombocytopenia (10.2%) and neutropenia (6.2%). For patients receiving chidamide combined with chemotherapy, grade 3 to 4 AEs that occurred in ≥5% of patients included thrombocytopenia (18.1%), neutropenia (12.6%), anemia (7.1%), and fatigue (5.5%). This large real-world study demonstrates that chidamide has a favorable efficacy and an acceptable safety profile for refractory and relapsed PTCL patients. Chidamide combined with chemotherapy may be a new treatment choice for refractory and relapsed PTCL patients but requires further investigation.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin's lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton's tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/ CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the response and outcome of patients with multiple myeloma (MM) and to analyze the factors influencing the prognosis of the disease. Retrospective analysis was performed in 27 patients with MM who had been treated by ASCT (ASCT group) and 28 patients treated with combined chemotherapy only (non-ASCT group) from May 2004 to August 2011. The impact on the depth of response, progression-free survival (PFS) and overall survival (OS) times, as well as associated prognostic factors of patients with MM, were analyzed. All patients successfully underwent hematopoietic reconstruction without transplantation-related mortality. The complete remission (CR) rate of patients in the ASCT group significantly increased from 25.9% (7/27) before ASCT to 70.4% (19/27) following ASCT (P<0.01). The probability of OS for 5 years was 52.2% for the patients in the ASCT group and 33.1% for those in the non-ASCT group (P>0.05). Univariate analysis in the ASCT group demonstrated that maintenance and consolidation therapies were associated with significant increases in PFS (P=0.01) and OS (P<0.01) times. The present study demonstrated that ASCT further increases the CR rate, prolongs PFS time and potentially increases the OS time. Incorporation of these novel agents, including the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide, into the induction, consolidation and maintenance phases has optimized the anti-myeloma activity of ASCT. [ABSTRACT FROM AUTHOR]

Background: Biphenotypic acute leukemia (BAL) is a rare type of acute leukemia that presents with a high degree of heterogeneity and is not well defined. Methods: We identified 51 cases (3%) of BAL from 1,693 newly diagnosed acute leukemia patients according to the EGIL scoring system. The immunophenotyping, cytogenetics, treatment, and outcome of 39 BAL patients were retrospectively analyzed. Results: There were 23 (59%) cases of the myeloid and B-lymphoid phenotype, 14 (36%) cases of the myeloid and T-lymphoid phenotype, and 1 case (3%) of the trilineage phenotype or B/T phenotype. Abnormal karyotypes were detected in 76% of the 37 validated patients and displayed a high degree of heterogeneity. Combined regimens for both acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), as well as ALL type regimens, appeared to achieve a better complete remission rate than AML type regimens (71 and 64 vs. 33%, respectively). BAL patients with complex karyotypes or a rearrangement of chromosome 11 had a significantly reduced survival rate in comparison to patients with normal, t(8; 21), or t(9; 22) karyotypes. The probability of overall survival and disease-free survival at 2 years was 26 and 18%, respectively. Conclusions: Our findings indicate that BAL shows a high incidence of abnormal karyotypes and a poor prognosis. Combined-type regimens or ALL-based protocols are effective for the treatment of BAL. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]