Untreated Peripheral T-cell Lymphomas Research Articles

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

Romidepsin Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Versus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Final Analysis of the Ro-CHOP Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The primary analysis of the Ro-CHOP phase III randomized controlled trial (ClinicalTrials.gov identifier: NCT01796002) established that romidepsin (Ro) plus cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) did not yield an increased efficacy compared with CHOP alone as first-line treatment of peripheral T-cell lymphoma. We report the planned final analysis 5 years after the last patient enrolled. With a median follow-up of 6 years, median progression-free survival (PFS) was 12.0 months compared with 10.2 months (hazard ratio [HR], 0.79 [95% CI, 0.62 to 1.005]; P = .054), while median overall survival was 62.2 months (35.7-86.6 months) and 43.8 months (30.1-70.2 months; HR, 0.88 [95% CI, 0.68 to 1.14]; P = .324) in the Ro-CHOP and CHOP arms, respectively. In an exploratory analysis, the median PFS in the centrally reviewed follicular helper T-cell lymphoma subgroup was significantly longer in the Ro-CHOP arm (19.5 v 10.6 months, HR, 0.703 [95% CI, 0.502 to 0.985]; P = .039). Second-line treatments were given to 251 patients with a median PFS2 and OS2 after relapse or progression of 3.3 months and 11.5 months, respectively. Within the limits of highly heterogeneous second-line treatments, no specific regimen seemed to provide superior disease control. However, a potential benefit was observed with brentuximab vedotin in association with chemotherapy even after excluding anaplastic large-cell lymphoma subtype or after adjusting for histology and international prognostic index in a multivariate model (HR for PFS, 0.431 [95% CI, 0.238 to 0.779]; P = .005).

Chidamide with Azacitidine and CHOP Treatment Plus Autologous Transplantation,Followed By Maintenance with Chidamide for Patients with Newly Diagnosed Peripheral T-Cell Lymphoma: Interim Analysis of a Prospective,Single Center,Single-Arm, Phase 2 Trial

Background: The standard first-line treatment for peripheral T-Cell Lymphoma (PTCL) is cyclophosphamide, doxorubicin, vincristine, and prednison (CHOP)，but the treatment effect is poor,the 5-year overall survival(OS) was only 30-40%.We aimed to evaluate the efficacy and safety of chidamide with azacitidine and CHOP treatment plus autologous stem-cell transplantation and of maintenance treatment with chidamide in newly diagnosed peripheral T-Cell Lymphoma (PTCL). Methods: This is an ongoing prospective,single center，single-arm, phase 2 trial. We enrolled newly diagnosed PTCL patients (NK/T lymphoma and ALK positive T cell lymphoma were excluded )and used 21-day Chi+AZ-CHOP regimen for induction therapy.Subjects received CHOP on day 1 combined with azacitidine 100mg was subcutaneous injected daily for 5 days and oral chidamide 20mg two times per week of each cycle. 17 subjects received PEG-rhG-CSF Supportive care after treatment.These subjects who evaluated PR or CR remission after 4 to 6 courses of induction therapy will perform autologous hematopoietic stem cell transplantation(ASCT), followed by oral chidamide 20mg two times per week maintance. The primary endpoints is ORR per 2014 IWG criteria.Secondary endpoints include CR, safety and survival. Results:From 3/2021 to 7/2023, 35 subjects with previously untreated PTCL were enrolled in chongqing university cancer hospital, and the study met its accrual.At study entry, 22 patients (62.8%) were angioimmu-noblastic T-cell lymphoma(AITL),4 patients (11.4%) was monomorphic epitheliotropic intestinal T-cell lyphomas(MEITL),3 patients (8.6%) were Peripheral T Cell Lymphoma, Not Otherwise Specified（PTCL-nos），2 patients (5.7%) was Mycosis fungoides(MF),4 patients(11.4%) was anaplastic large cell lymphoma; ALK-negative（ALCL-ALK).The median age was 55 years (range 27-70),and the M:F ratio was 1.5:1. 26 patients (74.3%) had stage Ⅲ/Ⅳ disease, 6 (17.1%) had bone marrow involvement, and 11 (31.4%) had IPI 3-5.By July 2023, 3 subjects did not return to the hospital for further treatment after the first cycle. 32 subjects received Chi+AZ-CHOP regimen treatments at least 2 cycles,median treatment cycles were 4 cycles. 2 subjects progressed during the treatment, 10 subjects were performed with autologous hematopoietic stem cell transplantation. The ORR was 87.5% with CR at 46.9%(n=32) .The assessment after autologous hematopoietic stem cell transplantation(n=10), ORR was 100 % and CR was 90%.To date, Evaluation of outcomes in patients with AITL at the end of induction(n=17), ORR was 94.1% and CR was 52.9%. Treatment was generally well tolerated with expected side exects.The most common grade 3-4 hematologic adverse events were neutropenia（45%），febrile neutropenia (40%)，anemia (25%) and thrombocytopenia (15%) ,Grade 3-4 non-hematologic toxicities included hypokalemia（35%）,nausea(30%), vomiting (20%),fatigue (30%),and elevated ALT (4.8%).No treatment-related deaths have been studied so far. C onclusion: This trail proved that chidamide combined with azacytidine +CHOP is feasible and safe in the treatment of peripheral T-cell lymphoma. Especially，achieved a high CR rate in the induction therapy phase of AITL subtype. Although neutropenia is the most common adverse reaction, it is generally safe and controllable.

High Rates of Remission with the Initial Treatment of Oral Selinexor Plus CHOP for Newly Diagnosed Peripheral T-Cell Lymphoma (PTCL): Clinical Outcomes Analysis of a Multi-Center Phase II Study in China

CONCLUSIONS Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of aggressive lymphoproliferative disorders with dismal clinical outcomes. In China, PTCLs account for over 20% of non-Hodgkin lymphoma (NHL) cases, representing a relatively high incidence. Although CHOP-like regimens remain the standard frontline therapy, their efficacy is limited (Alain Mina, 2022). Previous studies have demonstrated high expression of XPO1 in T-NHL cell lines and potent anti-proliferative effects of the selective inhibitor selinexor at nanomolar concentrations (Abeykoon JP, 2019). Here, we report the safety and preliminary efficacy of combining selinexor with CHOP as first-line treatment in previously untreated PTCL patients (ChiCTR2200057942). In this open-label, multicentre, phase 2 trial, we enrolled patients with previously untreated peripheral T-cell lymphoma (PTCL). Participants received standard CHOP chemotherapy on day 1 of each cycle for 6 or 8 cycles, along with selinexor priming at 40 or 60 mg on days 1, 8 and 15. Patients achieving a complete response (CR) or partial response (PR) at the end of induction treatement (EOI), with or without autologous stem cell transplantation (ASCT), and then received maintenance treatment with selinexor (days 1, 8, 15 and 22 every 28 days) for up to 12 months. The primary endpoint was overall response rate (ORR) during induction, and secondary endpoints included CR rate, duration of response (DOR), PFS, OS and safety. Between Jul 1, 2022 and May 21, 2023, a total of 17 previously untreated PTCL pts were enrolled and received treatment at six centers, including seven with AITL (41.2%), six with PTCL-NOS (35.3%). The median age was 52 years (range 30-67), 11 (64.7%) had stage III/IV disease, with nine (52.9%) pts having IPI 2-5. As of July 10, 2023, with a median follow-up of 7.3 months (range 1.9-14.8 months), three pts discontinued treatment without efficacy evaluation (two pts due to bone marrow suppression, one pt due to COVID-19 infection), and one pt died due to disease progression. Among 12 pts evaluable for the primary endpoint, seven pts (58.3%) achieved CR, four pts (33.3%) had PR, one pt (9.1%) experienced progressive disease (PD). Based on the analysis of different subtype, the ORR and CR was 100% (5/5) and 80% (4/5) in AITL, 100% (4/4) and 25% (1/4) in PTCL-NOS. One ALK+ALCL and one PTCL-TFH patient achieved CR, while one SPTCL patient experienced progressive disease. Among the 12 pts who received the initial dose of 60mg, two pts did not complete the third course of treatment due to myelosuppression, and two pts reduced the dose to 40mg due to adverse reactions. Five pts in the 40mg group did not require dose reduction or withdrawal. The ORR was 87.5% (7/8) and the CR rate was 62.5% (5/8) in the 60 mg group. The ORR was 100% (4/4) and the CR rate was 50% (2/4) in the 40 mg group. Pts in the 40mg group had better tolerance and similar efficacy compared to those in the 60mg group. The most common (≥10%) Grade 3 or 4 treatment-related adverse events (AEs) were neutropenia (29%), thrombocytopenia (24%), and anemia (18%). No fatal AEs were reported at the end of follow-up, the median PFS and OS were not reached. The integration of Selinexor into the standard tri-weekly CHOP chemotherapy regime has shown a manageable safety profile along with encouraging anti-tumor activity in patients with previously untreated PTCL. The trial is currently ongoing, and this manuscript presents the preliminary findings.

Multicenter phase 2 study of romidepsin plus lenalidomide for previously untreated peripheral T-cell lymphoma

AbstractPeripheral T-cell lymphomas (PTCLs) are associated with poor prognosis when treated with cytotoxic chemotherapy. We report the findings of a phase 2 study evaluating a chemotherapy-free combination of romidepsin plus lenalidomide as initial treatment for patients with PTCL who were aged >60 years or noncandidates for chemotherapy. Treatment was initiated with romidepsin 10 mg/m2 IV on days 1, 8, and 15 and lenalidomide 25 mg taken orally from days 1 to 21 of 28-day cycle for up to 1 year. The primary objective was overall response rate (ORR). Secondary objectives included safety and survival. The study enrolled 29 patients with a median age of 75 years, including 16 (55%) angioimmunoblastic T-cell lymphoma (AITL), 10 (34%) PTCL– not otherwise specified, 2 ATLL, and 1 EATL. Grade 3 to 4 hematologic toxicities included neutropenia (45%), thrombocytopenia (34%), and anemia (28%). Grade 3 to 4 nonhematologic toxicities included hyponatremia (45%), hypertension (38%), hypoalbuminemia (24%), fatigue (17%), hyperglycemia (14%), hypokalemia (14%), dehydration (10%), and infection (10%). At median follow-up of 15.7 months, 23 patients were evaluable and received a median treatment of 6 cycles. The ORR was 65.2% with complete response (CR) at 26.1%, including 78.6% ORR and 35.7% CR for AITL. Median duration of response was 10.7 months, with 27.1 months for patients achieving CR. The estimated 2-year progression-free survival was 31.5%, and 2-year overall survival was 49.5%. This study provides the first demonstration that the biologic combination of romidepsin and lenalidomide is feasible and effective as initial therapy for PTCL and warrants further evaluation. This trial was registered at www.clinicaltrials.gov as #NCT02232516.

A multi-institutional prospective cohort study of minimal residual disease in peripheral T-cell lymphoma: Impact of autologous stem cell transplant.

7563 Background: Roughly 80% of pts with peripheral T-cell lymphomas (PTCL) respond to CHOP-based therapy but 5-yr survival ranges between 20-40%. The high relapse rate after complete response (CR) suggests more sensitive response assessment, such as minimal residual disease (MRD) testing, could have prognostic or predictive value. Next generation sequencing (NGS) of the T-cell receptor (TCR) can detect a known TCR clonotype at 10-5. In a prospective study, we evaluated the utility of MRD testing via TCR NGS in PTCL (NCT03297697). Here we report results for pts pre- and post-autologous stem cell transplant (ASCT). Methods: This investigator-initiated, multi-institutional, prospective cohort study assessed MRD testing by TCR NGS in PTCL. Pts with previously untreated PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), PTCL with T-follicular helper (TFH) phenotype, or monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) treated with anthracycline-based curative-intent therapy were eligible. Baseline TCR (TRG or TRB) clonotypes were established from diagnostic tissue or peripheral blood if tissue was not available. TCR clonality was determined positive via the LymphoTrack TRG/TRB Assays – MiSeq (Invivoscribe, San Diego, CA) when top % reads were ≥2.5% and ≥2x above background. Samples were obtained at diagnosis (pre-treatment), following induction therapy (EOT/pre-ASCT), and serially post-ASCT. Results: Of 43 enrolled pts, 19 underwent consolidative ASCT, of which 10 had post-ASCT samples available for MRD testing (Table). Median age at ASCT was 62 years (range: 38-77). Baseline TCR clonotypes were identified in 10/10 pts. At pre-ASCT evaluation, 7/10 pts had detectable TCR MRD (‘pos’) and 3/10 pts had TCR MRD below the level of detection (‘neg‘). Of the 3 MRD neg pts pre-ASCT, 2 had CR and 1 had PR by PET-CT. All 7 TCR MRD pos pts pre-ASCT had CR by PET-CT. Of 7 MRD pos pts pre-ASCT, 6 remained MRD pos and 1 became MRD neg post-ASCT. Of the 4 MRD neg pts post-ASCT, none have relapsed at 52, 31, 34, and 31 mo post-ASCT. Of 7 MRD pos pts pre-ASCT, 3 have relapsed following ASCT (at 3, 9, and 29 mo post-ASCT). Conclusions: In this cohort of patients with PTCL receiving consolidative ASCT in CR1, all 4 pts with negative TCR MRD post-ASCT remain in remission at median follow up of 32.5 mo post-ASCT. The negative predictive value of TCR NGS MRD post-ASCT should be further evaluated. Clinical trial information: NCT03297697 . [Table: see text]

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: The primary analysis of the Ro-CHOP trial (NCT01796002) demonstrated that romidepsine (Ro) plus CHOP did not provide an increased efficacy compared with CHOP alone in patients with previously untreated peripheral T-cell lymphoma (PTCL). We report here the final analysis of the Ro-CHOP trial. Methods: The study was an open-label multicenter randomized (1:1) phase III study of Ro-CHOP versus CHOP as frontline treatment of patients 18–80 years with PTCL. The primary endpoint was progression-free survival (PFS) according to IWG 1999 criteria. Overall survival (OS) was a secondary endpoint, relapse patterns and PFS/OS after the first progression (PFS2/OS2) were analyzed post-hoc. The cut-off date was set to 2022/12/13, that is, five years after the last patient was enrolled. Results: 211 and 210 patients were assigned to receive 6 cycles of Ro-CHOP or CHOP in 3-week cycles, respectively. Median age was 65 (25–81) years. With a median follow-up of 71.8 months, 271 patients (64.4%) presented a PFS event by independent RAC assessment. Median PFS was 12 months (95% CI = [9; 25.8]) and 10.2 months ([7.4; 13.2]) for Ro-CHOP and CHOP, respectively (HR = 0.79 [0.62; 1.005], p = 0.054, 2-sided p-value). Based on 229 deaths, median OS was 62.2 months and 43.8 months for Ro-CHOP and CHOP, respectively. The causes of death were the following: lymphoma (n = 165, 72.4%), concurrent illness (n = 30, 13.2%), other reasons (n = 12, 5.3%), toxicity of salvage treatment (n = 8, 3.5%), toxicity of study treatment (n = 4, 1.8%), unknown (n = 9, 3.9%). No new safety signal was observed. A significantly prolonged PFS in the follicular helper T-cell (TFH) lymphoma subgroup (centrally reviewed) was still observed with this longer follow-up. The median PFS was 19.5 months ([11.5; 44.4]) in the Ro-CHOP arm and 10.6 months ([7.4; 14.9) the CHOP arm with a HR of 0.703 ([0.502; 0.985], p = 0.0395). Additional treatment was given to 251 patients after progression (Ro-CHOP = 115, and CHOP = 136), leading to an overall response rate of 35.7% (CR/CRu: 21.7%) and 31.6% (CR/CRu: 22.1%) in the Ro-CHOP and CHOP groups, respectively. Overall, 191 of the 251 patients (76.1%) progressed after second-line therapy, and 20 patients died without a second progression (8.0%). The median PFS2 and OS2 were 3.3 months (95% CI, [2.7; 4.5]) and 11.5 months ([9.6; 15.9]), respectively. Twenty-three patients (9.2%) received an allogeneic stem cell transplantation (median age 51 [29–70] years) and displayed 1-year PFS2 and OS2 rates estimated at 59.7% and 81.8%, respectively. Detailed outcome according to salvage treatment at progression will be presented at the meeting. The study was sponsored by the LYSARC, with funding provided by Celgene/BMS Keyword: aggressive T-cell non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract V. Camus Consultant or advisory role: Roche, BMS, Novartis, Kite-Gilead, Janssen, Abbvie, Sanofi, Octapharma, Kyowa Kirin Pharma Research funding: Iqone Healthcare, BMS Educational grants: Pfizer, Roche, BMS, Novartis, Kite-Gilead M. Delfau-Larue Honoraria: Takeda, Amgen, Roche, Gilead, Abbvie Research Funding: Celgene, BMS, Roche

Long-time follow-up of patients with untreated peripheral T cell lymphoma following chidamide combined with cyclophosphamide, epirubicin, vindesine, prednisone, and etoposide therapy: a single-center propensity score-matching study

PurposeThis is a retrospective, single-center PSM study evaluating the efficacy and safety of chidamide combined with the CHOEP (C-CHOEP) regimen versus the single CHOEP regimen in patients with untreated peripheral T cell lymphomas (PTCL).PatientsPatients newly diagnosed with PTCL between January 2015 and June 2021 were recruited, and were 1:1 divided into C-CHOEP and CHOEP groups according to their first-line chemotherapy regimens. The PSM method was used to match the baseline variables to balance the confounding factors.ResultsA cohort of 33 patients each in the C-CHOEP and CHOEP groups was generated after propensity score-matching (PSM). The complete remission (CR) rates of the C-CHOEP regimen were higher than that of the CHOEP regimen (56.3 vs. 25.8%, p = 0.014), whereas the duration of response of the C-CHOEP group was shorter (median DOR 30 vs. 57 months), resulting in roughly similar progression-free survival (PFS) and (overall survival) OS between the two groups. The responding patients who received chidamide maintenance therapy showed a trend of superior PFS and OS compared with patients who did not receive maintenance therapy.ConclusionsThe C-CHOEP regimen was well tolerated but failed to show advantages over the CHOEP regimen in patients with untreated PTCL; however, the chidamide maintenance may contribute to a more durable response and stable long-term survival.

Romidepsin-CHOEP followed by high-dose chemotherapy and stem-cell transplantation in untreated Peripheral T-Cell Lymphoma: results of the PTCL13 phase Ib/II study

The standard treatment for young patients with untreated PTCLs is based on anthracycline containing-regimens followed by high-dose-chemotherapy and stem-cell-transplantation (HDT + SCT), but only 40% of them can be cured. Romidepsin, a histone-deacetylase inhibitor, showed promising activity in relapsed PTCLs; in first line, Romidepsin was added with CHOP. We designed a study combining romidepsin and CHOEP as induction before HDT + auto-SCT in untreated PTCLs (PTCL-NOS, AITL/THF, ALK-ALCL), aged 18–65 years. A phase Ib/II trial was conducted to define the maximum tolerated dose (MTD) of Ro-CHOEP, and to assess efficacy and safety of 6 Ro-CHOEP as induction before HDT. The study hypothesis was to achieve a 18-month PFS of 70%. Twenty-one patients were enrolled into phase Ib; 7 dose-limiting toxicities were observed, that led to define the MTD at 14 mg/ms. Eighty-six patients were included in the phase II. At a median follow-up of 28 months, the 18-month PFS was 46.2% (95%CI:35.0–56.7), and the 18-month overall survival was 73.1% (95%CI:61.6–81.7). The overall response after induction was 71%, with 62% CRs. No unexpected toxicities were reported. The primary endpoint was not met; therefore, the enrollment was stopped at a planned interim analysis. The addition of romidepsin to CHOEP did not improve the PFS of untreated PTCL patients.

A Multicenter, Phase III Study of Chidamide, Azacitidine Combined with CHOP Versus CHOP in Patients with Untreated Peripheral T-Cell Lymphoma

Introduction The biology of peripheral T-cell lymphoma (PTCL) is characterized by recurrent mutations affecting epigenetic regulators such as TET2, DNMT3A, IDH2, and RHOA, particularly in patients with angioimmunoblastic T-cell lymphoma (AITL) or PTCL-not otherwise specified. Azacitidine, a DNA methyl transferase (DNMT) inhibitor, has shown clinical activity as a single agent and in combination in R/R PTCL. Single-agent of the histone deacetylase (HDAC) inhibitors, including romidepsin, belinostat, and chidamide are associated with overall response rates of 25-30% in R/R PTCL. These evidence suggests that PTCL may have a unique vulnerability to epigenetic modulators which also provide the rationale for combining an HDAC inhibitor with a DNMT inhibitor in the backbone of the CHOP regimen forming a novel double-epigenetic regulating chemotherapy as an initial treatment for PTCL. Herein, we report the finding of the phase III trial of chidamide and azacitidine combined with CHOP (AC-CHOP) versus CHOP in patients with untreated PTCL (ClinicalTrials.gov - NCT05075460). Methods This study is a multicenter, non-randomized, phase III trial conducted at 4 centers in China. Eligible patients were aged between 18-75 years with newly diagnosed PTCL. Patients were non-randomly assigned to the AC-CHOP or the CHOP group according to the investigator's and patient's choice. Patients in the AC-CHOP group received azacitidine 200 mg subcutaneously on days 1-2 and 100 mg on day 3, chidamide 20mg orally twice weekly, combined with the CHOP regimen in a 3-week cycle for six cycles. Patients in the CHOP group received the CHOP regimen alone. The primary endpoint was the overall response rate (ORR) after the protocol treatment. Results Between August 2021 and March 2022, 35 patients were enrolled in the study and finished protocol treatment (20 in the AC-CHOP arm and 15 in the CHOP arm). Main pathological subgroups were PTCL not specified (n = 14) and AITL (n = 21). The baseline characteristics and pathological subtypes were mostly similar between the two treatment arms. At the end of treatment, the ORR and complete response (CR) rates were 60.0% and 55.0% in the AC-CHOP arm versus 53.3% and 26.7% in the CHOP arm (P = 0.693 for ORR and P = 0.184 for CR rate) , respectively. With a median follow-up time of 9 months, the median progression-free survival was 8 months in the AC-CHOP arm and 7 months in the CHOP arm (P = 0.602). The most frequent grade 3 to 4 adverse events included neutropenia (55.0% in the AC-CHOP arm versus 40.0% in the CHOP arm), thrombocytopenia (20.0% in the AC-CHOP arm versus 13.3% in the CHOP arm), and Anemia (5.0% in the AC-CHOP arm versus 6.7% in the CHOP arm) which showed no significant difference between the two arms. Conclusions According to the preliminary result of the study, the addition of azacytidine and chidamide to the CHOP regimen did not show a significant improvement of ORR or PFS for patients with untreated PTCL. A trend of higher CR rate was observed which did not reach statistical significance. The safety profile of AC-CHOP regimen was manageable.

Chidamide with Azacitidine and CHOP Treatment Plus Autologous Transplantation, Followed By Maintenance with Chidamide for Patients with Newly Diagnosed Peripheral T-Cell Lymphoma (PTCL): Interim Analysis of a Prospective,Single Center, Single-Arm, Phase 2 Trial

Background: The standard first-line treatment for peripheral T-Cell Lymphoma (PTCL) is cyclophosphamide, doxorubicin, vincristine, and prednison (CHOP)，but the treatment effect is poor,the 5-year overall survival(OS) was only 30-40%.We aimed to evaluate the efficacy and safety of chidamide with azacitidine and CHOP treatment plus autologous stem-cell transplantation and of maintenance treatment with chidamide in newly diagnosed peripheral T-Cell Lymphoma (PTCL). Methods: This is an ongoing prospective,single center，single-arm, phase 2 trial. We enrolled newly diagnosed PTCL patients (NK/T lymphoma and ALK positive T cell lymphoma were excluded )and used 21-day Chi+AZ-CHOP regimen for induction therapy.Subjects received CHOP on day 1 combined with azacitidine 100mg was subcutaneous injected daily for 5 days and oral chidamide 20mg two times per week of each cycle. 6 subjects received PEG-rhG-CSF Supportive care after treatment.These subjects who evaluated PR or CR remission after 4 to 6 courses of induction therapy will perform autologous hematopoietic stem cell transplantation(ASCT), followed by oral chidamide 20mg two times per week maintance. The primary endpoints is ORR per 2014 IWG criteria.Secondary endpoints include CR, safety and survival. Results: From 3/2021 to 5/2022, 20subjects with previously untreated PTCL were enrolled in chongqing university cancer hospital, and the study met its accrual.At study entry, 16 patients (80%) were angioimmu-noblastic T-cell lymphoma(AITL),1 patient(5%) was monomorphic epitheliotropic intestinal T-cell lyphomas(MEITL),1 patient(5%) was Mycosis fungoides(MF).The median age was 58 years (range 46-70),and the M:F ratio was 1.5:1. Nineteen (90%) had stage III/IV disease, 4 (20%) had bone marrow involvement, and 11 (55%) had IPI 3-5.By July 2022, 1 subject did not return to the hospital for further treatment after the first cycle. 16 subjects had once efficacy evaluation at least ,3 subjects progressed during the treatment, 5 subjects were performed with autologous hematopoietic stem cell transplantation. At interim assessment after cycle 4 induction therapy (n=13), the ORR was 69% with CR at 46% .The assessment after autologous hematopoietic stem cell transplantation(n=5), ORR was 100 % and CR was 100%.To date, Evaluation of outcomes in patients with AITL at the end of induction(n=8), one of the subjects did not return to the hospital for further treatment after the first cycle,ORR was 87.5% and CR was 62.5%. Treatment was generally well tolerated with expected side exects.The most common grade 3-4 hematologic adverse events were neutropenia（45%），febrile neutropenia (40%)，anemia (25%) and thrombocytopenia (15%) ,Grade 3-4 non-hematologic toxicities included hypokalemia（35%）,nausea(30%), vomiting (20%),fatigue (30%),and elevated ALT (4.8%).No treatment-related deaths have been studied so far. Conclusion: This trail proved that chidamide combined with azacytidine +CHOP is feasible and safe in the treatment of peripheral T-cell lymphoma. Especially，achieved a high CR rate in the induction therapy phase of AITL subtype. Although neutropenia is the most common adverse reaction, it is generally safe and controllable.

P1187: END OF TREATMENT 18F FDG-PET/CT RESPONSE IS PROGNOSTIC FOR OVERALL AND PROGRESSION-FREE SURVIVAL IN PERIPHERAL T-CELL LYMPHOMA: RESULTS OF THE UK NCRI PHASE 2 RANDOMISED CHEMO-T TRIAL PET/CT SUBSTUDY

Background: The role of 18F FDG PET (PET) in peripheral T-cell lymphoma (PTCL) remains under evaluation. The UK NCRI phase 2 randomised CHEMO-T trial compared cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) with gemcitabine, cisplatin and methylprednisolone (GEM-P) in previously untreated PTCL patients. The primary endpoint, to demonstrate a superior complete response (CR) rate for GEM-P by contrast-enhanced CT (CECT) at end of treatment (EOT) was not met. Aims: To investigate the role of PET in determining baseline bone marrow (BM) involvement in PTCL and as a prognostic tool at EOT. Methods: Patients required a baseline PET (acquired as per protocol) within 28 days of randomisation and a PET at EOT at least 28 days post chemotherapy. Site accreditation, data collation, and quality control for PET imaging was performed by the UK PET Core Lab. BM biopsy was required within 6 weeks of randomisation. PET scans were centrally reviewed at The Royal Marsden by 2 expert nuclear medicine physicians (YD and NH). Baseline BM involvement by PTCL on PET was evaluated. PET response was assessed according to the revised response criteria for malignant lymphoma and by the Deauville score (DS) 5-point scale. Where discordance existed between reviewers, a third reviewer (SC) adjudicated. EOT PET response and PET status (DS 1-3=PET-negative, DS 4-5=PET-positive) were correlated with PFS and OS. Results: Baseline PET data was available for 82/84 patients, 80/82 (98%) had FDG-avid disease (n=2 with non-avid disease (n=1 AITL, n=1 EATL) were excluded). Clinical characteristics were similar to the main trial cohort: median age=63 yrs, male=73% and high-risk IPI=23%. PTCL subtypes were AITL n=33 (41%), PTCL-NOS n=32 (40%), ALK- ALCL n=14 (18%) and EATL n=1 (1%). For 20/79 (25%) patients with biopsy-proven BM infiltration 9/19 (47%) had BM uptake on baseline PET. Of 20/80 patients (25%) with BM uptake on baseline PET, 9/20 (45%) had biopsy-confirmed infiltration. PET had a sensitivity of 47% and a specificity 81% for determination of BM involvement. EOT PET was available for 69/80, n=4 were excluded as data was acquired following a later line (n=3) or complete imaging was not retrievable (n=1); therefore 65/80 had evaluable EOT PET data. The median number of days from EOT to PET was 41. At EOT, PET response was CR n=41 (63%), partial response (PR) n=15 (23%), stable disease n=0 and progressive disease (PD) n=9 (14%); 41 (63%) were PET-negative and 24 (37%) were PET-positive. At a median follow-up of 27 months, PET-negative vs. PET-positive patients at EOT had a 2-yr OS of 72% vs. 52% [HR 0.58; 95% CI 0.24–1.41), p=0.231] and 2-yr PFS of 55% and 29% [HR 0.45 (95% CI 0.23–0.88), p=0.021] respectively. EOT PET response correlation with 2-yr OS was CR=72%, PR=67%, PD=29%; and with 2-yr PFS was CR=55%, PR=32%, PD=25%. A CR by PET (vs. PD) was associated with improved OS [HR 0.245 (95% CI 0.083–0.730), p=0.012] (Figure 1) and PFS [HR 0.265 (95% CI 0.102–0.687), p=0.006]. Adjusting for stratification parameters at randomisation (IPI risk group, PTCL subtype) PET response remained prognostic for both OS and PFS while EOT PET status (positive vs. negative) did not. CECT response remained prognostic for PFS only. Image:Summary/Conclusion: Our findings indicate that PET has insufficient sensitivity for detection of BM involvement for baseline staging. Furthermore, while both EOT CECT and PET response were prognostic for PFS and OS, only PET response remained prognostic for OS following adjustment for stratification factors suggesting it is a superior prognostic tool in PTCL.

High Rates of Remission with the Initial Treatment of Oral Azacitidine Plus CHOP for Peripheral T-Cell Lymphoma (PTCL): Clinical Outcomes and Biomarker Analysis of a Multi-Center Phase II Study

High Rates of Remission with the Initial Treatment of Oral Azacitidine Plus CHOP for Peripheral T-Cell Lymphoma (PTCL): Clinical Outcomes and Biomarker Analysis of a Multi-Center Phase II Study

End of Treatment Peripheral Blood TCR Evaluation for Minimal Residual Disease Evaluation in Peripheral T-Cell Lymphomas

End of Treatment Peripheral Blood TCR Evaluation for Minimal Residual Disease Evaluation in Peripheral T-Cell Lymphomas

The Combination of Bortezomib with Cyclophosphamide, Epirubicin, Etoposide and Prednisone (BCHEP) Regimen As First-Line Treatment for Untreated Patients with Peripheral T Cell Lymphoma: A Prospective, Single Arm, Phase II Study

Background: Peripheral T-cell lymphoma (PTCL) is a clinically and biologically heterogeneous disease with poor prognosis. The response rate of standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisolone) is only 50-60%, with a poor long-term survival rate of 10-30%. The addition of etoposide to CHOP increases response rate, but not progression free survival (PFS) or overall survival (OS). Recent study reported that nuclear factor kappa B (NF-κB) pathway plays a critical role in PTCL. Bortezomib, a potent and reversible proteasome inhibitor, can induce tumor cell apoptosis by inhibiting activation of NF-κB pathway and has been recommended as single agent option in relapse/refractory PTCL. We aimed to study the efficacy and safety of bortezomib in combination with cyclophosphamide, doxorubicin, etoposide, and prednisone (BCHEP) in newly diagnosed PTCL patients for the first time.METHODS: A prospective, single arm, phase 2 study was conducted (NCT04061772). This is an interim analysis. Patients with newly diagnosis of PTCL were treated with up to 6 cycles of BCHEP regimen every 3 weeks. Bortezomib was subcutaneously administered on Days 1 and 8 at a dose of 1.3 mg/m 2 in combination with CHEP， consisting of 100 mg/m 2 etoposide on Days 1 to 3, 750mg/m 2 cyclophosphamide on Day 1, 75mg/m 2 epirubicin on Day 1 and 100mg prednisone on Days 1 to 5. The primary endpoint of the study was ORR including complete response (CR) and partial response (PR). The secondary endpoints included progression free survival (PFS), overall survival (OS) and adverse events (AEs).RESULTS: Between February 2019 and January 2021, a total of twenty-six patients were enrolled. Median age was 57 years (range 37-69) and six (23.1%) were female. Pathological subtypes included ALK-positive anaplastic cell lymphoma (ALCL, n=2), ALK-negative ALCL (n=4), PTCL, not otherwise specified (PTCL-NOS, n=9) and angioimmunoblastic T-cell lymphoma (AITL, n=11). Nineteen patients had stage III/IV disease and eleven had B symptoms, including weight loss in three cases and fever in eight. Ten patients had elevated serum lactate dehydrogenase (LDH), eleven had IPI score higher than 2. All patients had completed BCHEP treatment for at least two cycles and received imaging evaluation. Ten patients received prophylaxis of intrathecal chemotherapy with methotrexate at least once. Three patients received consolidated radiotherapy for metabolic residuals after chemotherapy, while one received autologous hematopoietic stem cell transplantation as consolidation treatment. This study had reached the primary end point at this interim analysis. The ORR was 92.3% (24/26) with a CR rate of 57.7% (15/26). Two patients had progression of disease within two cycles of chemotherapy. After a median follow-up of 16.3 months, twelve patients had disease progression, and six died. Median PFS was 10.9 months and 1-year PFS rate was 65.4%. Median OS was 14.6 months and 1-year OS rate was 88.5%. No patient presented with Grade 5 AE. The most frequent all-grade hematological toxicity was leucopenia (42.3%,11/26), anemia (50%,13/26) and thrombocytopenia (23.1%, 6/26). Other common toxicity included intestinal infection or pneumonia (19.2%, 5/26), Grade 1 peripheral neuropathy (15.4%, 4/26) and nausea (7.7%, 2/26). Dose reduction was performed in eight patients.CONCLUSIONS: Interim results showed that bortezomib in combination with CHEP is associated with high response rate and manageable toxicity in patients with previously untreated PTCL. The BCHEP regimen may serve as a novel first-line treatment option for patients with PTCL. The study is going on to enroll patients and updating results, including the prognostic value of serum inflammatory factors. Larger trials will be necessary to further verify the efficacy of this regimen in treatment naïve PTCL patients and to overcome relapse after remission. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

TCL-150: The ECHELON-2 Trial: 5-Year Results of a Randomized, Double-Blind, Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in Frontline Treatment of Patients with CD30-Positive Peripheral T-Cell Lymphoma

Objective Brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) significantly prolonged progression-free survival (PFS) and overall survival (OS) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with systemic anaplastic large-cell lymphoma (sALCL) or other CD30-positive peripheral T-cell lymphomas (PTCL) in ECHELON-2 (Horwitz S et al., Lancet 2019). We report updated results; median follow-up was 47.6 months for PFS and 66.8 months for OS. Design This phase 3, double-blind study (NCT01777152) randomized patients aged ≥18 years with previously untreated CD30-positive PTCL (targeting 75% ± 5% with sALCL) to A+CHP or CHOP for 6 or 8 cycles. Primary endpoint of PFS was assessed per investigator in this updated analysis. Key secondary endpoints included OS and PFS in sALCL. BV or BV-containing regimens were permitted as subsequent/retreatment therapies. Results 452 patients were enrolled (226 patients in each arm); 316 (70%) patients had sALCL. Patients with advanced disease were included (stage III [27%] and stage IV [53%]; International Prognostic Index ≥2 [78%]). Data continues to favor A+CHP: HRs were 0.70 (95% CI: 0.53–0.91, P=0.0077) for PFS per investigator and 0.72 (95% CI: 0.53–0.99, P=0.0424) for OS. 5-year PFS was 51.4% (95% CI: 42.8–59.4) with A+CHP versus 43.0% (95% CI: 35.8–50.0) with CHOP; median PFS was 62.3 months (95% CI: 42.0–not evaluable) with A+CHP and 23.8 months (95% CI: 13.6–60.8) with CHOP. 5-year OS was 70.1% (95% CI: 63.3–75.9) and 61.0% (95% CI: 54.0–67.3) with A+CHP and CHOP, respectively. Median OS was not reached in either arm. PFS favored A+CHP (HR: 0.55 [95% CI: 0.39–0.79]) in sALCL. 29 (13%) and 54 (24%) patients with A+CHP and CHOP received subsequent BV, respectively. Treatment-emergent peripheral neuropathy (PN), resolved/improved in 72% (n=84/117) and 78% (n=97/124) of patients with PN on A+CHP and CHOP, respectively; 98% and 97% of ongoing PN events were grade 1/2 with A+CHP and CHOP, respectively. Conclusions At this important 5-year milestone, A+CHP still provides clinically meaningful improvement in both PFS and OS versus CHOP, with a manageable safety profile, including continued resolution/improvement of PN. Funded by NIH/NCI Support Grant P30 CA008748.

Next-generation sequencing–based monitoring of circulating tumor DNA reveals clonotypic heterogeneity in untreated PTCL

Peripheral T-cell lymphomas (PTCLs) have marked biologic and clinical heterogeneity, which confounds treatment decisions. Advances in circulating tumor DNA (ctDNA) assays using next-generation sequencing (NGS) have improved the detection of molecular relapse and driver mutations in diffuse large B-cell lymphoma and show the potential utility of ctDNA across lymphomas. We investigated NGS-based monitoring of T-cell receptor (TCR) sequences in patients with PTCL undergoing frontline treatment. Of 45 patients, 34 (76%) had tumor-specific clonotypes of the TCRβ or TCRγ genes identified, which included 18 (86%) from baseline tissue and 16 (67%) from baseline serum. Twenty-five (74%) patients had both TCRβ and TCRγ clonotypes, 23 (68%) had more than 1 TCRγ clonotype, and 4 (9%) had multiple TCRβ or TCRγ clonotypes, demonstrating significant intrapatient clonotypic heterogeneity. Among 24 patients with available serial serum samples during treatment, 9 (38%) cleared ctDNA after 2 cycles of therapy, and 11 (46%) had detectable ctDNA at the end of treatment. Patients with detectable ctDNA after therapy showed a trend toward worse survival. Notably, 2 patients with persistently detectable ctDNA after therapy remained in remission with 10 years of follow-up. Clonotypic heterogeneity in tumors and persistence, despite long-term remission, suggests variability in oncological potential. This trial was registered at www.clinicaltrials.gov as #NCT00001337.

Next-Generation Sequencing Based Monitoring of Circulating-Tumor DNA in Untreated Peripheral T-Cell Lymphoma

Background: Peripheral T-cell lymphomas (PTCLs) are aggressive lymphomas with a wide range of clinical outcomes. Overall prognosis is worse for PTCL than B-cell lymphomas, but pts who achieve remission can be cured. After initial therapy, controversy exists regarding consolidation with autologous stem cell transplant, and clinical decisions are largely empirical. Circulating-tumor DNA (ctDNA) is emerging as a promising non-invasive biomarker that may aid clinical decision-making. Quantitative baseline levels of ctDNA and kinetics of ctDNA clearance during therapy may provide prognostic information. Further, novel methods that detect disease relapse prior to imaging may improve outcomes. We studied a high-throughput DNA sequencing method of detecting T-cell receptor (TCR) β and γ gene sequences in serum with a sensitivity of 1 lymphoma molecule per million leukocytes. Using this platform, we determined the predictive ability of monitoring ctDNA in pts undergoing frontline therapy for PTCL.Methods: All pts had PTCL undergoing frontline EPOCH-based chemotherapy between May 1993 through December 2015. Pre-treatment FFPE biopsy samples and/or baseline serum samples were sent for VDJ amplification and TCR sequencing calibration. High-throughput TCR sequencing of the CDR3s of TCRβ/TCRγ genes was employed to provide a comprehensive and quantitative analysis of distinct T-cell clones within each sample, the relative frequency of each clone, and the exact unique nucleotide sequences of each clone's CDR3 regions. Pts with a calibrating TCRβ/TCRγ sequence had all available serum samples sent for identification and quantification. Prospectively collected serum sample time points included baseline, start of each cycle, and each follow-up visit until disease progression. Clinic visits after therapy included paired contrast CT scans performed at 3, 4, 6, 12 and 12 mos. intervals for the first 5 years, respectively. All analyses for ctDNA were performed blinded to clinical outcomes.Results: Fifty PTCL pts had a pre-treatment FFPE or serum sample available for calibration. Nineteen of 23 (83%) pts with pre-treatment FFPE had a calibrating rearrangement; Fourteen of 27 (52%) pts with only pre-treatment serum available had a calibrating rearrangement; 1 pt who did not calibrate on FFPE had a dominant sequence identified in serum. Overall, tumor-specific clonotypes were identified in 34 (68%) of 50 pts tested. Ten of 18 (56%) pts with both FFPE and serum available had dominant clones in both compartments. Of the 44 calibrating pre-treatment samples, 1 calibrated for TCRβ only, 15 for TCRγ only, and 28 for both loci. Pt characteristics shown in Table 1. Of 34 study pts, 20 (59%) progressed and 14 (41%) were non-progressors. Quantitative baseline ctDNA levels were significantly higher in pts with stage IV disease compared to stages I-III (p=0.014) but did not correlate with LDH levels (p=0.53).We analyzed the predictive ability of ctDNA as a measure of minimal residual disease (MRD) within 1 month of completing therapy in 28 pts. We compared pts who became MRD- to those who remained MRD+ and identified a trend towards improved PFS in those who became MRD- (median, NR vs. 208 days, p=0.07) (Figure 1). In 20 pts who achieved remission, we studied the use of ctDNA monitoring as a surveillance tool. Of the 10 pts who progressed after remission, ctDNA was detected prior to clinical relapse in 6 cases with a median lead-time of 13.2 mos. (range, 2.7 to 88.5) and 4 with detectable ctDNA > 12 mos. prior to clinical relapse. Four pts progressed without detectable ctDNA prior to clinical relapse. Interestingly, of the 10 non-progressors followed in surveillance, 5 pts developed low-level ctDNA positivity without clinical progression. Results of interim ctDNA kinetics and TCRβ testing is ongoing and will be presented at the meeting.Conclusions: Next-generation based sequencing of the TCR can identify tumor-specific clonotypic sequences in the majority of pts from both FFPE and serum. As a marker of MRD, monitoring TCR sequences in serum may identify pts who do not benefit from treatment intensification, but further studies are needed. Surveillance monitoring of ctDNA in serum identifies TCR sequences months before clinical progression but not all pts with clonotypic sequences progressed clinically in our series. Further studies are needed to investigate surveillance monitoring methods and optimize clinical utility. [Display omitted] DisclosuresJacob:Adaptive Biotechnologies: Employment, Equity Ownership. Chan:Adaptive Biotechnologies: Employment. Vignali:Adaptive Biotechnologies: Employment.

A Phase II Study of THP-COP (pirarubicin, cyclophosphamide, vincristine and prednisolone) in Patients with Newly Diagnosed Advanced Peripheral T-Cell Lymphoma: THP-3 Study of Japan Hematopoietic Malignancy Clinical Study Group (HMCSG)

BackgroundAlthough CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) has been established as a standard of care in patients (pts) with newly diagnosed peripheral T-cell lymphoma (PTCL), new treatment regimen or strategy has been awaited since the outcome of pts with PTCL treated with CHOP is still poor. Pirarubicin (THP) is, an anthracycline drug, which is not affected by the multidrug resistance mediating p-glycoprotein, and is less cardiotoxic than doxorubicin. THP exhibits activity against some doxorubicin-resistant cell lines.ObjectiveA multicenter phase II study was conducted to evaluate the efficacy and toxicity of THP-COP (pirarubicin, cyclophosphamide, vincristine and prednisolone) therapy in pts with newly diagnosed PTCL by Japan Hematopoietic Malignancy Clinical Study Group.Patients and MethodsEligibility criteria were as follows; newly diagnosed PTCL including PTCL-not otherwise specified (NOS), anaplastic large cell lymphoma (ALCL) and angioimmunoblastic T-cell lymphoma (AITL); clinical stage of bulky II, III or IV; aged 20 to 79 years; PS 0-2 by ECOG's scale. THP-COP consists of pirarubicin (50mg/m2 on Day1), cyclophosphamide (750mg/m2 on Day1), vincristine (1.4mg/m2 max. 2mg, on Day 1) and prednisolone (100mg on Days 1 to 5) every 3 weeks up to 8 cycles in younger pts less than 69 years, and 6 cycles in elderly pts aged 70 to 79 years, The primary endpoint was complete response rate (%CR) including unconfirmed CR (CRu). The planned sample size was 40 pts, which provided at least 80% power with the expected %CR of 55%, threshold of 35%, and a one-sided α of 5%.ResultsFrom October 2007 to December 2012, 41 pts with a median age of 63 (21-77) yrs were enrolled. The numbers of pts with PTCL-NOS, AITL and ALCL was 21 (51%), 14 (34%) and 6 (15%), respectively. The numbers of stage II bulky, III and IV was 2 (5%), 22 (54%) and 17 (41%), respectively.Fifty-four % were International Prognostic Index high/intermediate or high risk. The %CR including %CRu and overall response rate were 51.2% (90% CI; 37.4-64.9) which met the primary endpoint, and 70.7% (95% CI; 54.5-83.9), respectively. The progression-free survival and overall survival at 3 years (3-yr PFS and 3-yr OS) were 43.5% (95% CI; 27.5-58.4) and 62.9% (95% CI; 43.3-77.4), respectively. Most common Grade 4 toxicities were hematologic: %Grade 4 neutropenia and thrombocytopenia were 80.5% and 9.8%, respectively. Cardiac adverse events were observed in 2 patients with Grade 1 arrhythmia. No secondary malignancies were observed.ConclusionsIn pts with untreated advanced PTCL including PTCL-NOS, AITL and ALCL, THP-COP demonstrated high efficacy with durable PFS and OS and acceptable toxicity profiles. Further large-scaled randomized study to compare with CHOP is warranted. DisclosuresOgura:Celgene: Consultancy, Honoraria; Mundipharma: Consultancy; Takeda: Consultancy, Honoraria; Astrazeneca: Honoraria; SymBio: Consultancy, Research Funding; Celltrion, Inc: Consultancy, Honoraria; MeijiSeika Pharma: Consultancy. Ohmachi:Kyowa Hakko Kirin Co., Ltd.: Honoraria; Eisai Co., Ltd.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Pfizer Inc: Honoraria; Takeda Pharmaceutical Co., Ltd: Honoraria. Suzuki:MundiPharma: Consultancy; Chugai Pharmaceutical: Honoraria; Sawai Pharmaceutical: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Mochida Pharmaceutical: Honoraria; MSD: Honoraria; Jazz Pharmaceuticals: Consultancy; Kyowa-Hakko Kirin: Honoraria; Shionogi: Honoraria; Meiji Seika Pharma: Honoraria; Ohtsuka: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Takeda Pharmaceuticals: Honoraria; Bristol-Myers Squibb: Honoraria; Gilead Sciences: Consultancy. Atsuta:Otsuka Pharmaceutical Co., Ltd.: Honoraria. Ohyashiki:Chugai: Research Funding; Dainippon Sumitomo: Honoraria; Nippon Shinyaku: Honoraria; Celegen: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria; Novartis pharma: Honoraria; Novartis: Research Funding; Asteras: Research Funding; Taiho pharmaceutical: Honoraria; Alexion: Honoraria; MSD: Honoraria; Otsuka pharmaceutical: Honoraria; Jansen Pharma: Honoraria, Research Funding; Pfizer: Honoraria; Fujirebio: Honoraria; KyowaHakko Kirin: Honoraria, Research Funding. Hidaka:Chugai: Research Funding; Eisai: Honoraria. Ando:NIHON PHARMACEUTICAL: Other: Donation to institute; Nippon Shinyaku: Other: Donation to institute; Japan Blood Products Organization: Other: Donation to institute; Takeda: Other: Donation to institute; ALEXION: Other: Donation to institute; Kyowa Hakko Kirin: Other: Donation to institute; MSD: Other: Donation to institute; Bristol-Myers Squibb: Other: Donation to institute; Eisai: Other: Donation to institute; Sumitomo Dainippon Pharma: Other: Donation to institute; CHUGAI PHARMACEUTICAL: Other: Donation to institute; Meiji Seika Pharma: Other: Donation to institute; NOVARTIS: Other: Donation to institute; MOCHIDA PHARMACEUTICAL: Other: Donation to institute; TOYAMA CHEMICAL: Other: Donation to institute; TAIHO: Other: Donation to institute; Asahi KASEI: Other: Donation to institute. Fukuhara:Nihon Ultmarc, Astellas, AbbVie, Alexionpharma, Bayer Yakuhin, Bristol-Myers Squibb, Baxalta, Celgene, Chugai, Daiichi-Sankyo, Toehringer Ingelheim, Eisai, GlaxoSmithKline, Janssen, Japan Blood Products Organization, Kyowa Hakko Kirin, Mitsubishi Tanabe, : Research Funding; Eisai, Janssen, Takeda, Ono and Zenyaku Kogyo: Honoraria. Morishita:Celgene: Honoraria; Kyowa Hakko Kirin: Honoraria. Tsukasaki:Takeda: Honoraria, Research Funding; Kyowa-Kirin: Honoraria; DaiichiSankyo: Consultancy; Zenyaku Kogyo: Honoraria; Celgene: Honoraria, Research Funding; Mundypharma: Research Funding; HUYA: Honoraria; Chugai/Roche: Honoraria. Ozawa:Kyowa Hakko Kirin: Honoraria; Janssen Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria. Hotta:SymBio: Consultancy; SellSeed: Other: outside director; Jansen Pharma: Honoraria; Meiji Seika Pharma: Honoraria; Zenyaku Kogyo: Honoraria. Kinoshita:Chugai: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Zenyaku: Honoraria, Research Funding; Jansen Pharma: Honoraria; Kyowa Hakko Kirin: Honoraria; Eisai: Honoraria; Bristol-Meier's-Squib: Honoraria; Solaisia: Research Funding; MSD: Research Funding; Takeda: Research Funding.

CHOP Chemotherapy Plus Campath-1H (CHOP-C) as First Line Treatment in Patients with Peripheral T-Cell Lymphoma (PTCL).

Malignant T-cells show very high CD 52 expression, and promising results have been obtained in T-PLL and in Sezary patients (pts) treated with alentuzumab (Campath ®). Here we report the preliminary results of standard CHOP therapy plus Campath (CHOP-C) in untreated PTCL pts. Starting from January 2003, 20 consecutive PTCL pts were treated by CHOP for 8 courses, preceded on day -1 by Campath 30 mg. s.c. The diagnosis was PTCL-U in 13 pts, AILD-T in 5, and ALCL Alk- in 2. Clinical characteristics of the 20 pts: mean age 53.3 years (28–69), stage III-IV in 18, bulky in 2, B-symptoms in 9, high LDH in 11, bone marrow attainment in 8, aaIPI 2–3 in 10 pts. 15/20 pts are valuable for the analysis. After a median follow-up of 253 days (105–773), 10/15 pts are still alive and 5/15 have died of lymphoma. 8/15 achieved CR 1 PR and 1 MR; 5 pts showed progression; 3/5 pts in Pro,1 pt in RP, and 1 pt in MR have died of lymphoma. 2 pts. relapsed +62 and +119 days after CR. The median OS and DFS were 461 and 264 days, respectively (Fig. 1). No toxic death was recorded. WHO grade 4 neutropenia was seen in 38/90 courses (42%), grade 4 thrombocytopenia in 4/90 (4%), CMV reactivation in 15/90 (17%), local erythema in 2/90, mild fever in 5/90. Major infections were J-C virus reactivation in 1 pt, pulmonary Invasive Aspergillosis in 1, sepsis in 1, pneumonia in 1. The feasibility of CHOP-C in PTCL pts aged up to 70 years has been proven, and the toxicity acceptable; however the efficacy of this regimen should be confirmed on a larger cohort of pts. [Display omitted]