scholarly journals Duvelisib in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma from the Phase 2 Primo Trial: Results of an Interim Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2456-2456
Author(s):  
Jonathan E Brammer ◽  
Pier Luigi Zinzani ◽  
Jasmine Zain ◽  
Monica Mead ◽  
Carla Casulo ◽  
...  
Keyword(s):  
T Cell ◽  
Interim Analysis ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Advisory Board ◽  
T Cell Lymphoma ◽  
Dose Optimization ◽  
Phase 2 ◽  
Peripheral T Cell Lymphoma ◽  
Expansion Phase

Abstract Relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) is a family of aggressive lymphomas, with a median overall survival (OS) of less than 6 months. Current FDA approved therapies for R/R PTCL have modest overall response rates (ORR) of < 30%. Duvelisib (DUV), a dual PI3K-δ,γ inhibitor, is FDA approved at 25 mg twice daily (BID) for the treatment of R/R chronic lymphocytic leukemia and R/R follicular lymphoma. On 10/3/2019, DUV received orphan designation for treatment of patients with R/R T-cell lymphomas. In the Phase 2, open-label, multi-center, parallel cohort PRIMO trial of DUV in R/R PTCL, the initial results of the dose-optimization phase (N=33) demonstrated a 54% ORR in the 75 mg BID (N=13) and 35% in the 25 mg BID (N=20) cohorts, respectively, by investigator assessment (INV). (NCT03372057; supported by Secura Bio). The expansion phase of PRIMO has a targeted enrollment of ~125 pts. Expansion phase eligibility criteria included histologically confirmed R/R PTCL after >1 cycle of a prior standard regimen, a CD4 lymphocyte count of ≥ 50/mm 3 and required PJP prophylaxis. HSV/VZV prophylaxis was strongly recommended. Based on the dose optimization results, pts in the expansion phase receive DUV at 75 mg BID for 2 cycles to maximize rapid tumor control, followed by 25 mg BID to maintain long-term disease control and mitigate late toxicities, until progressive disease (PD) or unacceptable toxicity. The primary endpoint is ORR by IRC assessment, and secondary endpoints include ORR by INV assessment, duration of response (DOR), PFS, OS, disease control rate, and safety; all analyses consisted of pts that received at least 1 dose of DUV. This analysis is from an interim data cutoff as of May 21, 2021 that includes the first 6 months of data for the 78 patients included in the analysis. Pts had a median age of 66.5 years (range, 21-92 years) and a median of 3 prior lines of therapy (range, 1-7). The ORR by IRC assessment was 50% (39/78 patients) and the CR rate was 32.1% (25/78 patients), see Table 1. 14 patients (18%) remained on treatment; 37 pts discontinued due to PD (47.4%), 15 discontinued to due adverse events (19.2%) , 4 died (5.1%), and 1 each discontinued for secondary malignancy, lack of response, and withdrawal of consent. 5 patients (6.4%) discontinued therapy to undergo stem cell transplant, which suggests that DUV may be used as a bridge to transplant for appropriate patients. There were 3 deaths related or possibly related to duvelisib: pneumonitis, Epstein-Barr associated lymphoproliferative disorder, and sepsis. The most frequent > Grade 3 adverse events seen were neutropenia (38.5%), ALT/AST increased (24.4%/ 21.8%), rash (7.7%), lymphocyte count decreased (7.7%), and sepsis (6.4%), see Table 2. ALT and/or AST elevations were the most common AEs leading to treatment discontinuations (N=12, 15.4%). The interim results of the first 78 patients in the PRIMO expansion phase show an ORR of 50% and a CR rate of 32%, which suggests this therapy is superior to currently available SOC therapeutic options. Duvelisib was well tolerated in this population and remained consistent with the known safety profile of DUV. These data, from a large diverse population of T cell lymphoma patients, build upon prior reports demonstrating DUV as an active oral treatment for pts with RR PTCL. Data from this interim analysis may be updated prior to the abstract presentation. Figure 1 Figure 1. Disclosures Brammer: Celgene: Research Funding; Kymera Therapeutics: Consultancy; Seattle Genetics: Speakers Bureau. Zinzani: BMS: Other: Advisory board, Speakers Bureau; ROCHE: Other, Speakers Bureau; SANDOZ: Other: Advisory board; ADC Therap.: Other; SERVIER: Other: Advisory board, Speakers Bureau; JANSSEN-CILAG: Other: Advisory board, Speakers Bureau; GILEAD: Other: Advisory board, Speakers Bureau; CELLTRION: Other: Advisory board, Speakers Bureau; EUSAPHARMA: Consultancy, Other, Speakers Bureau; TAKEDA: Other: Advisory board, Speakers Bureau; KYOWA KIRIN: Other, Speakers Bureau; NOVARTIS: Consultancy, Other, Speakers Bureau; TG Therapeutics: Other: Advisory board, Speakers Bureau; MSD: Consultancy, Other: Advisory board, Speakers Bureau; Incyte: Other, Speakers Bureau; Beigene: Other, Speakers Bureau; VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau. Zain: Secura Bio, Ono , Legend, Kiyowa Kirin, Myeloid Therapeutics Verastem Daichi Sankyo: Consultancy; Secura Bio, DaichiSankyo, Abbvie: Research Funding; Kiyoaw Kirin, Secura Bio, Seattle Genetics: Honoraria. Casulo: BMS: Research Funding; Verastem: Research Funding; Genentech: Research Funding; Gilead: Research Funding. Jacobsen: Takeda: Consultancy; Syros: Consultancy; Janssen: Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding. Gritti: Takeda: Consultancy; Roche: Consultancy; Kite Gilead: Consultancy; IQvia: Consultancy; Italfarmaco: Consultancy; Clinigen: Consultancy. Litwak: Secura Bio: Current Employment. Cohan: Secura Bio: Current Employment. Katz: Secura Bio: Current Employment. Mehta-Shah: C4 Therapeutics: Consultancy; Roche/Genentech: Research Funding; Kiowa Hakko Kirin: Consultancy; Karyopharm: Consultancy; Innate Pharmaceuticals: Research Funding; Celgene: Research Funding; Bristol Myers Squibb: Research Funding; AstraZeneca: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Secura Bio: Consultancy, Research Funding; Ono Pharmaceuticals: Consultancy; Corvus Pharmaceuticals: Research Funding; Verastem: Research Funding. Horwitz: ADC Therapeutics, Affimed, Aileron, Celgene, Daiichi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium /Takeda, Seattle Genetics, Trillium Therapeutics, and Verastem/SecuraBio.: Consultancy, Research Funding; Affimed: Research Funding; Aileron: Research Funding; Acrotech Biopharma, Affimed, ADC Therapeutics, Astex, Merck, Portola Pharma, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle Genetics, Shoreline Biosciences, Inc, Takeda, Trillium Th: Consultancy; Celgene: Research Funding; C4 Therapeutics: Consultancy; Crispr Therapeutics: Research Funding; Daiichi Sankyo: Research Funding; Forty Seven, Inc.: Research Funding; Kura Oncology: Consultancy; Kyowa Hakko Kirin: Consultancy, Research Funding; Millennium/Takeda: Research Funding; Myeloid Therapeutics: Consultancy; ONO Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Research Funding; Secura Bio: Consultancy; Shoreline Biosciences, Inc.: Consultancy; Takeda: Consultancy; Trillium Therapeutics: Consultancy, Research Funding; Tubulis: Consultancy; Verastem/Securabio: Research Funding. OffLabel Disclosure: Duvelisib is approved in relapsed/refraction CLL/SLL and FL. This study evaluates duvelisib in PTCL

scholarly journals A Phase II Study of Nivolumab in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 467-467 ◽  
Author(s):  
N. Nora Bennani ◽  
Levi D Pederson ◽  
Pamela Atherton ◽  
Ivana Micallef ◽  
Joseph P. Colgan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Interim Analysis ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Advisory Board ◽  
T Cell Lymphoma ◽  
Number Of Patients ◽  
Hyperprogressive Disease

Introduction: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of mature aggressive T-cell non-Hodgkin lymphomas. They carry a worse prognosis for most subtypes compared with their B-cell counterparts. Despite the recent approval of newer therapies, the response rate and duration of clinical benefit is short and the outlook for patients with relapsed/refractory (RR) PTCL remains poor. There is therefore a need for novel effective therapies in PTCL. Targeting the profoundly immunosuppressive tumor microenvironment (TME) in PTCL is one such approach. Preclinical data show that malignant cells in PTCL overexpress programmed death ligand 1 (PD-L1), which signals via programmed death-1 (PD-1) receptor, and provides an inhibitory signal further suppressing antitumor immunity. PD-1/PD-L1/2 interactions in PTCL are particularly complicated as both the receptor and ligands can be expressed on the malignant T-cell. While the use of anti-PD-1 blocking antibodies has shown remarkable efficacy particularly in relapsed Hodgkin lymphoma, only a small number of patients with PTCL have been treated with checkpoint blockade. We conducted an investigator-initiated phase 2 prospective study of single-agent nivolumab for RR PTCL. We report here the results of the prespecified interim analysis. Study design and patient selection: Nivolumab was given at a flat dose of 240 mg intravenously (IV) every 2 weeks for 8 cycles then 480 mg IV every 4 weeks starting cycle 9. The primary objective was to assess the overall response rate (ORR) defined as proportion of subjects achieving either a partial response (PR) or complete response (CR) within 12 cycles of treatment. Secondary objectives were to assess safety and tolerability of nivolumab in PTCL and to assess progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Pre-planned sample size was 39, assuming that an ORR of 10% or less would be considered negative and an ORR of 30% or greater would warrant further study. We used a one-stage design with an interim analysis (upon enrolling 12 subjects) based on a Simon optimal design to assess efficacy. This design had a 90% power with a 1-sided 10% level test. The Duffy and Santner method was utilized to determine confidence intervals for the ORR. Kaplan-Meier methods were used to assess PFS, OS, and DOR. This study was sponsored by Bristol-Myers Squibb (NCT03075553). Results: Twelve patients who received at least one cycle of nivolumab were included in this interim analysis. Patient characteristics are illustrated in table 1. Half (6/12) of the patients had angioimmunoblastic T-cell lymphoma (AITL), 3/12 had PTCL, not otherwise specified (NOS), one had ALK negative anaplastic large cell lymphoma (ALK- ALCL). Most (11/12) were advanced stage (stage 4), had extranodal disease and half of the patients had received a prior autologous transplant. The ORR was 33% (4/12) (95% CI: 12.3 - 63.7%): 1 CR seen in ALK-ALCL; 2 PR, 1 in PTCL, NOS and 1 in enteropathy associated T-cell lymphoma; 1 CR in AITL. The median DOR was 3.6 months (95% CI: 1.9-6.9). The median PFS for all 12 patients was short at 1.9 months (95% CI: 1.5-8.7); median OS was 7.9 months (95% CI: 3.4-10.8) (Panel A). Hyperprogressive disease (defined as dramatic progression within 1 cycle of treatment) occurred in 4 patients. Observed grade 3 and higher adverse events (AEs) were as follows: non-hematologic AEs in 5/12 (41.7%), while hematologic AEs were seen in 3/12 (25%) patients. Conclusions: Nivolumab had modest clinical activity in patients with R/R PTCL and the study met the criteria at interim analysis to continue accrual. However, due to the high number of patients with hyperprogressive disease, the moderate activity of the drug, and short DOR, a decision was made to halt the study. These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases. Further studies are indicated using nivolumab in combination (rather than a single-agent) and use of biomarkers to better predict the responders. Disclosures Bennani: Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board. Nowakowski:Selvita: Membership on an entity's Board of Directors or advisory committees; NanoString: Research Funding; Celgene: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Curis: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Genentech, Inc.: Research Funding; MorphoSys: Consultancy, Research Funding. Ansell:Merck: Other: research funding for clinical trials; Seattle Genetics: Other: research funding for clinical trials; Takeda: Other: research funding for clinical trials; Bristol Myers Squibb: Other: research funding for clinical trials; Regeneron: Other: research funding for clinical trials; Affimed: Other: research funding for clinical trials; Pfizer: Other: research funding for clinical trials; AI Therapeutics: Other: research funding for clinical trials.

Brentuximab vedotin in The Treatment of Relapsed/Refractory CD30+ Peripheral T‐cell Lymphoma: a FIL Phase 2 Study

2022 ◽  
Author(s):  
Vittorio Stefoni ◽  
Cinzia Pellegrini ◽  
Lisa Argnani ◽  
Paolo Corradini ◽  
Anna Dodero ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Peripheral T Cell Lymphoma ◽  
Phase 2 Study

scholarly journals Impact of Comorbidities on Outcomes of Peripheral T Cell Lymphoma in Elderly Patients: An International Retrospective Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Monica Mead ◽  
Henrik Cederleuf ◽  
Thomas Relander ◽  
Mats Jerkeman ◽  
Fredrik Ellin ◽  
...  
Keyword(s):  
T Cell ◽  
Elderly Patients ◽  
Cause Of Death ◽  
Research Funding ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Rank Test ◽  
Peripheral T Cell Lymphoma ◽  
Cutaneous Lymphomas ◽  
Ann Arbor

Background: Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphoid neoplasms with poor outcomes. Many patients are elderly with increased comorbidities. Single-center retrospective studies describe outcomes in elderly PTCL patients and suggest comorbidity adversely affects outcomes. Little is known about the treatment, outcomes and impact of comorbidity in a large cohort of elderly PTCL patients. This study aims to describe outcomes of elderly PTCL patients in a large unselected international patient cohort. Methods: Patients with PTCL age ≥ 70 diagnosed from January 1, 2010 - December 31, 2015 in the Swedish Lymphoma Registry (SLR) and California Cancer Registry (CCR) were identified. The SLR covers ~ 95% of adult lymphoma patients in Sweden and the CCR includes information on all cancers diagnosed in California. Patients with precursor T-cell malignancies, primary cutaneous lymphomas, and leukemic subtypes were excluded. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI) and clinical outcomes of the cohort were extracted. Statistical analysis: Patient characteristics, clinical variables and outcomes were summarized using descriptive statistics and compared by Chi-square or Fisher's exact test. Outcomes of interest included overall survival (OS) and cause of death. Kaplan-Meier estimates of OS stratified by groups were calculated and presented in figures. Median OS was reported with 95% confidence interval (CI). Comparisons between groups for OS were done by log-rank test. Univariate and multiple Cox proportional hazards models provided hazards ratio estimates and 95% CI for risk factors. Tests for significance were two-tailed and a p-value less than the 0.05 significance level was considered statistically significant. Analyses were performed using software SAS version 9.4 (2013). Results: A total of 839 patients were included (SLR, n = 176, CCR, n = 663). Median age was 78 (SLR) and 79 (CCR) years, respectively. Included subtypes were AITL, n = 226; ALCL, n = 122; EATL, n = 31; Hepatosplenic TCL, n = 7; NK/T-cell lymphoma, n = 10; and PTCL NOS, n = 443. ECOG performance status was not available. CCI data was available in 731 patients (87 %), and CCI scores were divided into groups = 0-1 (61 %) and CCI > 1 (39 %). Male patients more often had a CCI score > 1 (p = 0.024). No other significant baseline differences were seen between the 2 groups (Table 1). Patients in the SLR more often received multiagent treatment compared to the CCR (63 % vs 44 %, p < 0.001). Age > 80 years, CCI > 1 and advanced Ann Arbor stage (III-IV) were significant prognostic factors for worse outcome. No difference in survival was seen between men and women nor the SLR and CCR (Table 2). Patients with a CCI >1 had a statistically significant worse survival compared to patients with a CCI =0-1 (0.36 years v 0.91 years, p=0.0001). Of the PTCL subtypes, AITL patients had a significantly better outcome (median OS = 1.26 years) compared to ALCL (OS = 0.57 years) and PTCL NOS (OS = 0.66 years). Patients receiving multiagent therapy had improved survival compared to patients not receiving multiagent therapy. When comparing OS in patients diagnosed in 2010-2012 with 2013-2015, no improvement was seen for the later period (Figures 1-4). Lymphoma was the most common cause of death with > 70 % of deaths related to lymphoma irrespective of CCI score (Table 3). Discussion: At the time of submission, this study presents the largest international cohort of elderly patients with PTCL. Prognosis is poor and comorbidity seems to further worsen . In contrast to younger patient series, patients with AITL had a better survival than patients with PTCL NOS and ALCL, and were more common in the CCR than in the SLR. Multiagent treatment was associated with improved outcome. A possible confounder could be that fit patients are also the ones receiving treatment, and it is a setback that adjustment for ECOG was not possible, making treatment data somewhat difficult to interpret. As expected, advanced stage (Ann Arbor III-IV) was associated with worse survival. Conclusion: We believe this is one of the largest cohorts presented in elderly patients with PTCL. Comorbidity is an important adverse factor in this group, whereas treatment seems to improve outcome. The majority of these patients die of lymphoma within a year from diagnosis, and development of new treatments represents an unmet clinical need. Disclosures Jerkeman: Abbvie: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Roche: Research Funding.

Final Results From a Pivotal, Multicenter, International, Open-Label, Phase 2 Study of Romidepsin In Progressive or Relapsed Peripheral T-Cell Lymphoma (PTCL) Following Prior Systemic Therapy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 114-114 ◽  
Author(s):  
Bertrand Coiffier ◽  
Barbara Pro ◽  
H. Miles Prince ◽  
Francine M Foss ◽  
Lubomir Sokol ◽  
...  
Keyword(s):  
T Cell ◽  
Board Of Directors ◽  
Systemic Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Open Label ◽  
Advisory Committees ◽  
Prior Systemic Therapy

Abstract Abstract 114 Background: Romidepsin is a potent HDAC inhibitor approved by the FDA for patients (pts) with cutaneous T-cell lymphoma who have received at least 1 prior systemic therapy. Durable clinical benefit and tolerability of romidepsin in pts with recurrent or refractory PTCL have been previously observed in a phase 2 trial conducted by the National Cancer Institute. The aim of this phase 2, single-arm, open-label registration study was to evaluate the activity of romidepsin in a larger number of pts with progressive or relapsed PTCL. Methods: Pts with histologically confirmed PTCL (PTCL NOS, angioimmunoblastic T-cell lymphoma, ALCL [ALK-1 negative], other subtypes) who failed or were refractory to ≥ 1 prior systemic therapy, and had measurable disease and ECOG performance status 0–2 were eligible. Exclusions included inadequate bone marrow or other organ function and significant cardiovascular abnormalities. Pts received romidepsin 14 mg/m2 as a 4-h IV infusion on days 1, 8, and 15 every 28 days for up to 6 cycles; treatment could be extended for stable disease (SD) or response. The primary endpoint was rate of complete response (CR + CRu) as evaluated by a central Independent Review Committee (IRC) using International Working Criteria for non-Hodgkin's lymphoma. IRC assessment consisted of a 2-step process, with initial radiographic review of images (CT, MRI) followed by an overall clinical assessment based on the radiology evaluations, photographs, and relevant clinical parameters. Secondary endpoints included objective response rate (ORR): CR + CRu + partial response (PR), investigator-assessed responses, duration of response, time to response, and safety. Results: 131 pts from 48 US, European, and Australian sites were enrolled and received at least 1 dose of romidepsin (as-treated population); 130 patients had histologically confirmed PTCL by central review. Mean age of all pts was 59.4 y (range, 20–83) and median time since diagnosis was 1.25 y (range, 0–17). Median number of prior systemic therapies was 2 (range, 1–8). 21 pts (16%) had failed a prior stem cell transplant. Responses assessed by the IRC are noted in the table below. Longest duration of response is 26+ mo and 16 (94%) of the 17 pts with a CR had not progressed as of the data cutoff (March 31, 2010). Investigator-assessed responses included 21 pts (16%) with CR + CRu, 18 pts (14%) with PR for an ORR of 30%. Currently, 13 pts continue to receive treatment (range, 10–36 cycles). Adverse events (AEs) were reported in 126 of 131 pts (96%). AEs reported in ≥ 20% of pts were nausea (59%), fatigue (41%), vomiting (38%), thrombocytopenia (38%), diarrhea (35%), pyrexia (34%), neutropenia (30%), anorexia (28%), constipation (28%), anemia (23%), and dysgeusia (21%). AEs ≥ grade 3 were reported for 86 pts (66%), with the most common (≥ 5%) being pneumonia (5%), pyrexia (5%), sepsis (5%), and vomiting (5%). 60 pts (46%) had at least 1 serious AE: the most frequently reported (≥ 5%) were pyrexia (7%), pneumonia (5%), vomiting (5%), and sepsis (5%). 22 pts (17%) withdrew due to AEs. 8 pts (6%) died within 30 days of the last dose of romidepsin; 1 death, due to sepsis, was assessed as possibly related to treatment. Conclusions: Complete and durable responses were observed with single agent romidepsin in pts with relapsed PTCL. These data support the therapeutic potential for romidepsin in relapsed PTCL and suggest that romidepsin is a strong candidate for inclusion in future novel regimens for these diseases. As of the data cutoff (March 31, 2010), the median duration of follow-up for CR is 8.2 mo. Disclosures: Coiffier: Gloucester: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Off Label Use: Romidepsin is indicated for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy. Romidepsin is not currently approved for the treatment of peripheral T-cell lymphoma (PTCL). Pro:Celgene: Research Funding. Prince:Celgene: Consultancy, Honoraria, Research Funding. Foss:Celgene: Consultancy; Eisai: Consultancy, Speakers Bureau; Merck: Speakers Bureau; Allos: Consultancy, Speakers Bureau; Cephalon: Speakers Bureau. Sokol:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Caballero:Celgene: Membership on an entity's Board of Directors or advisory committees. Morschhauser:Roche: Consultancy, Honoraria; Bayer: Honoraria. Padmanabhan:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Shustov:Celgene: Research Funding. Nichols:Celgene: Employment. Carroll:Celgene: Employment. Balser:Gloucester Pharmaceutical: Consultancy. Horwitz:Celgene: Consultancy, Honoraria.

Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE): First Detailed Report of Primary Treatment

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1614-1614 ◽  
Author(s):  
Francine M. Foss ◽  
Kenneth R. Carson ◽  
Lauren Pinter-Brown ◽  
Steven M. Horwitz ◽  
Steven T. Rosen ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Board Of Directors ◽  
Initial Treatment ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Primary Treatment ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Advisory Committees

Abstract 1614 Background: Registries can be invaluable for describing patterns of care for a population of patients. COMPLETE is a registry of peripheral T-cell lymphoma (PTCL) patients designed to identify the lymphoma-directed treatments and supportive care measures that PTCL patients receive. We report here the first detailed findings of initial therapy. Methods: This is a prospective, longitudinal, observational registry that is led by a global steering committee. Patients with newly diagnosed PTCL and providing written informed consent are eligible. Patients are entered into the registry from time of initial diagnosis and followed for up to 5 years. Only locked records are reported. Results: As of July 2012, 330 patients have been enrolled from the United States. The first patient was enrolled in February 2010. Locked baseline and treatment records are available for 124 and 81 patients, respectively. Of the 124 patients with locked baseline records, 67 patients (54%) were male, the mean age was 59 (range: 19–89), and race/ethnicity was recorded as: White (87 patients; 70%), Black (19; 15%), Asian (5; 4%) and other/unknown (13; 11%). Histology was reported as follows: PTCL-not otherwise specified (27%), anaplastic large cell lymphoma-primary systemic type (18%), angioimmunoblastic T-cell lymphoma (17%), transformed mycosis fungoides (7%), T/NK-cell lymphoma-nasal and nasal type (6%), adult T-cell leukemia/lymphoma, HTLV 1+ (6%) and other (19%). 25 patients (20%) had received another diagnosis, including B-cell lymphoma, Hodgkin's disease and other T-cell lymphomas, prior to their current diagnosis of PTCL. 49 patients (40%) had B symptoms, 102 patients (82%) had an Ann Arbor stage of III/IV, 116 patients (94%) had ECOG performance status of 0–1, and international prognostic index (IPI) score was distributed as follows: IPI 0 (7% of patients), 1 (15%), 2 (43%), 3 (26%), and 4 (9%). Of the 81 patients with locked treatment records, details on initial treatment can be found in table below. Conclusions: This first detailed analysis of primary treatment of PTCL indicates that this disease is still largely being treated with regimens derived primarily from studies of B-cell lymphomas and that a single standard of care does not exist. The fact that a meaningful proportion of patients were initially diagnosed with something other than their current diagnosis of PTCL points out the challenges of diagnosing the disease. While the intent of initial treatment for most patients is to affect a cure, more than 20% of patients were noted as deceased at the end of initial treatment, underscoring the need for more effective, disease-specific therapy. Disclosures: Foss: Merck: Study Grant, Study Grant Other; Celgene: Study Grant, Study Grant Other; Eisai: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy; Allos: Consultancy. Carson:Allos: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Pinter-Brown:Allos: Consultancy, Membership on an entity's Board of Directors or advisory committees. Horwitz:Allos: Consultancy, Research Funding. Rosen:Allos: Consultancy, Honoraria. Pro:Celgene: Honoraria, Research Funding; Spectrum: Honoraria; Allos: Honoraria; Seattle Genetics: Research Funding. Gisselbrecht:Allos: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hsi:Allos: Research Funding; Eli Lilly: Research Funding; Abbott: Research Funding; Cellerant Therapeutics: Research Funding; BD Biosciences: Research Funding; Millenium: Research Funding.

Population-Based Analysis of Elderly Patients (>70 YEARS) with Peripheral T-CELL Lymphoma: A Results from Czech Lymphoma Study Group (CLSG) Registry

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3000-3000 ◽  
Author(s):  
Andrea Janikova ◽  
Robert Pytlik ◽  
Pavel Klener ◽  
Zbynek Bortlicek ◽  
Vit Campr ◽  
...  
Keyword(s):  
T Cell ◽  
Elderly Patients ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Population Based ◽  
T Cell Lymphoma ◽  
First Line ◽  
Peripheral T Cell Lymphoma ◽  
Age Related

Abstract INTRODUCTION: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with usually poor prognosis. Age was identified as the independent risk factors in many studies. Elderly patients suffer from comorbidities, impaired organ functions, and poor performance status resulting in worse tolerance of therapy and its efficacy. Data on outcome, prognosis and treatment efficacy for elderly patients with PTCLs are sparse. METHODS: We used data of 941 newly diagnosed PTCLs registered into CLSG database between January 1999 and March 2015 with last follow-up in February 2016. CLSG database covers approximately 85% of all newly diagnosed NonHodgkin´s lymphomas (NHLs) in Czech Republic. For the analysis, 208 patients with age >70 years at diagnosis were selected. RESULTS: Totally, PTCLs accounted for about 8.7% (454/5210) patients of all NHLs in population younger 60 years, but only about 5.8% (208/3561) NHL patients older 70 years. Median age was 76ys (71-91ys), 94 (45%) were women, lactate dehydrogenase (LDH) was elevated in 130/208 (62.5%) pts., ECOG ≥2 had 80 (38%) pts., and advanced clinical stage III-IV presented 132/208 (63.5%) pts. We identified following PTCL subtypes: PTCL-NOS (Peripheral T-cell lymphoma not otherwise specified) 89/208 (43%), Anaplastic large cell lymphoma (ALCL) 34/208 (16.3%), Cutaneous Anaplastic large cell lymphoma (C-ALCL) 10/208 (4.8%), Mycosis fungoides/ Sézary syndrome (MF/SS) together 29/208 (14%), NK/T nasal lymphoma (NK/T) 2/208 (1%), Angioimmunoblastic lymphoma (AITL) 17/208 (8.1%), Cutaneous CD30+ T lymphoproliferative disease 1/208 (0.5%), T-lymphoblastic lymphoma/leukemia (T-LBL) 3/208 (1.4%), T-cell lymphoma without specification (T-NHL) 17/208 (8.1%). Distribution of PTCL subtypes changed significantly with age. There was higher proportion of PTCL-NOS (43% vs. 34%; p.001) and MF/SS (14% vs. 4.8%; p<.001) in elderly patients (>70ys) compared to younger cohort (≤70ys; n=725). Contrary, percentage of ALCL (16.3% vs. 27%; p<.001) with main difference in ALK+ cases (2% vs. 11%; p<.001), and NK/T (1% vs. 5%; p.003) was lower in elderly PTCLs, whereas the incidence of AITL (8.1% vs. 6.6%) or EATL (3.4% vs. 3%) was similar in both age subgroups. For the whole cohort of PTCLs (>70ys), the 5-year overall survival (OS) was 30% and 5-year progression free survival (PFS) was 21% regardless of subtype or stage. Progression is fatal event in elderly patients with median survival about 8 months only. There were significant survival differences between patients (>70ys vs. ≤70ys) according to PTCL subtype; PTCL-NOS 5 yr-OS 23% vs. 43% (p.00001), ALCL ALK+ 5-yr OS not reached vs. 79% (p.01), ALCL ALK- 5 yr-OS 24% vs. 50% (p.001). Patients with AITL or EATL showed no age-related survival differences. First-line chemotherapy was administered in majority of cases (67%); CHOP-like regimen was given in 78 (37%) pts., COP-like in 44 (21%) pts., and other chemotherapy in 18 (9%) cases. Local therapy (surgery, radiotherapy) was administered in first line in 17 (8%) pts., no or palliative therapy (corticoids) was given in 34 (17%) pts., initial therapy was unknown in 17 (8%) cases. We compared two subgroups of patients according to first line chemotherapy CHOP (n=75) vs. COP (n=41). Median age was 74ys (71-84) vs. 79ys (71-89), high IPI was presented in 29% vs. 50% of patients (p.001). Complete response (CR) was achieved in 35/75 (47%) CHOP treated patients, and in 7/41 (17%) patients managed with COP (p.001). Contrary, there were 12/75 (16%) progression in CHOP arm compared to 10/41 (24%) COP treated pts. Five-year OS was 28% vs. 15% better in CHOP group (p.029) and 5-yr PFS 25% vs. 10%, respectively. CONCLUSIONS: In population-based analysis of adult Caucasian PTCL patients, we identified mild decreasing incidence with age. There were significant age-related distribution differences of PTCL subtypes with shift to preponderance of PTCL-NOS, Mycosis fungoides, and NK/T nasal lymphoma in elderly. Worse survival in elderly PTCLs in comparison to younger patients was evident especially for PTCL-NOS and ALCL subtypes. Despite the baseline differences (COP managed pts. had higher IPI), there is tendency that anthracycline-based chemotherapy (CHOP) brings better results with higher proportion of CR and lower progression/relapse rate projected in longer survival. Disclosures Belada: Seattle Genetics: Research Funding. Mayer:AOP Orphan Pharmaceuticals: Research Funding; Novartis: Research Funding.

scholarly journals 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

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2482-2482
Author(s):  
Haiyan Yang ◽  
Cong Li
Keyword(s):  
T Cell ◽  
Interim Analysis ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
T Cell Lymphoma ◽  
First Line ◽  
Peripheral T Cell Lymphoma ◽  
Free Survival ◽  
First Line Treatment

Abstract 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. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Frontline Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin and Prednisone in Patients with Peripheral T-Cell Lymphoma with Less Than 10% CD30 Expression (SGN35-032, Trial in Progress)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1401-1401
Author(s):  
Deepa Jagadeesh ◽  
Scott Knowles ◽  
Steven M. Horwitz
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
Efficacy And Safety ◽  
Time To Event ◽  
Peripheral T Cell Lymphoma ◽  
Secondary Endpoints

Abstract Background Brentuximab vedotin (BV) was the first antibody-drug conjugate to be approved in multiple cancer types (Gauzy-Lazo 2020). The combination of a CD30-directed monoclonal antibody, a protease-cleavable linker, and the microtubule-disrupting agent monomethyl auristatin E drives the anticancer activity of BV by inducing CD30-targeted cell cycle arrest and apoptosis as well as the bystander effect on adjacent cells (Sutherland 2006, Hansen 2016, Schönberger 2018). In the ECHELON-2 phase 3 clinical trial, BV, cyclophosphamide, doxorubicin, and prednisone (A+CHP) showed efficacy in patients with peripheral T-cell lymphoma (PTCL) across a range of CD30 expression levels, including the lowest eligible level of 10% by immunohistochemistry when compared with patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (Advani 2019). It is hypothesized that A+CHP will demonstrate efficacy in PTCL with &lt;10% CD30 expression because i) clinical responses to BV have occurred in patients with PTCL, cutaneous T-cell lymphoma, or B-cell lymphoma with low (&lt;10%) and undetectable CD30 expression (Jagadeesh 2019) and ii) CD30 expression levels were not predictive of A+CHP responses in non-systemic anaplastic large cell lymphoma (sALCL) (Advani 2019). Study Design and Methods SGN35-032 is a dual-cohort, open-label, multicenter, phase 2 clinical trial (NCT04569032) designed to evaluate the efficacy and safety of A+CHP in patients with non-sALCL PTCL and CD30 expression of &lt;10% on tumor cells. Up to approximately 40 patients will be enrolled in each of the CD30-negative (expression &lt;1%) and the CD30-low (expression ≥1% to &lt;10%) cohorts. Patients will be enrolled based on local results but only patients with CD30 expression &lt;10% per central confirmation will be analyzed for the primary and secondary endpoints. Patients will receive 21-day cycles of A+CHP for 6-8 cycles. Key inclusion criteria include adults with newly diagnosed PTCL, excluding sALCL, per the World Health Organization 2016 classification; CD30 expression &lt;10% by local assessment; and fluorodeoxyglucose-avid disease by positron emission tomography (PET) and measurable disease of at least 1.5 cm by computed tomography (CT), as assessed by the site radiologist. Patients with previous exposure to BV or doxorubicin will not be eligible. The primary endpoint of this trial is objective response rate (ORR) per blinded independent central review (BICR) using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Secondary endpoints include ORR by BICR using the modified Lugano criteria (Cheson 2014), complete response rate, progression-free survival (PFS), and duration of response per BICR using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007), overall survival, and safety and tolerability. A PET scan is required at baseline, after Cycle 4, and after the completion of study treatment. Follow-up restaging CT scans will be performed over the next 2 years. In both the CD30-negative and the CD30-low cohorts, efficacy and safety endpoints will be summarized using descriptive statistics to describe continuous variables by cohort. Time-to-event endpoints, such as PFS, will be estimated using Kaplan-Meier (KM) methodology and KM plots will be presented. Medians for time-to-event analyses (e.g., median PFS) will be presented and two-sided 95% confidence intervals will be calculated using the log-log transformation method. Enrollment is planned for 15 US sites and 32 sites across the Czech Republic, France, Italy, and the UK. Disclosures Knowles: Seagen Inc.: Current Employment. Horwitz: ADC Therapeutics, Affimed, Aileron, Celgene, Daiichi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium /Takeda, Seattle Genetics, Trillium Therapeutics, and Verastem/SecuraBio.: Consultancy, Research Funding; Affimed: Research Funding; Aileron: Research Funding; Acrotech Biopharma, Affimed, ADC Therapeutics, Astex, Merck, Portola Pharma, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle Genetics, Shoreline Biosciences, Inc, Takeda, Trillium Th: Consultancy; Celgene: Research Funding; C4 Therapeutics: Consultancy; Crispr Therapeutics: Research Funding; Daiichi Sankyo: Research Funding; Forty Seven, Inc.: Research Funding; Kura Oncology: Consultancy; Kyowa Hakko Kirin: Consultancy, Research Funding; Millennium/Takeda: Research Funding; Myeloid Therapeutics: Consultancy; ONO Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Research Funding; Secura Bio: Consultancy; Shoreline Biosciences, Inc.: Consultancy; Takeda: Consultancy; Trillium Therapeutics: Consultancy, Research Funding; Tubulis: Consultancy; Verastem/Securabio: Research Funding.

scholarly journals Nanatinostat (Nstat) and Valganciclovir (VGCV) in Relapsed/Refractory (R/R) Epstein-Barr Virus-Positive (EBV +) Lymphomas: Final Results from the Phase 1b/2 VT3996-201 Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 623-623
Author(s):  
Bradley M. Haverkos ◽  
Onder Alpdogan ◽  
Robert Baiocchi ◽  
Jonathan E Brammer ◽  
Tatyana A. Feldman ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Advisory Committees ◽  
Phase 1B

Abstract Introduction: EBV can be associated with several types of lymphomas, with reported frequencies of up to 8-10% in diffuse large B cell lymphoma (DLBCL), 30-100% in peripheral T cell lymphoma (PTCL) subtypes, 80% in post-transplant lymphoproliferative disease (PTLD), and 15-30% in classical Hodgkin lymphoma (HL), with adverse impact on outcomes. Nanatinostat (Nstat) is a Class-I selective oral HDAC inhibitor that induces the expression of the lytic BGLF4 EBV protein kinase in EBV + tumor cells, activating ganciclovir (GCV) via phosphorylation. This results in GCV-induced inhibition of viral and cellular DNA synthesis and apoptosis. Herein we report the final results from this exploratory study for patients with R/R EBV + lymphomas (NCT03397706). Methods: Patients aged ≥18 with histologically confirmed EBV + lymphomas (defined as any degree of EBER-ISH positivity), R/R to ≥1 prior systemic therapies with an absolute neutrophil count ≥1.0×10 9/L, platelet count ≥50×10 9/L, and no curative treatment options per investigator were enrolled into 5 dose escalation cohorts to determine the recommended phase 2 doses (RP2D) of Nstat + VGCV for phase 2 expansion. Phase 2 patients received the RP2D (Nstat 20 mg daily, 4 days per week + VGCV 900 mg orally daily) in 28-day cycles until disease progression or withdrawal. Primary endpoints were safety/RP2D (phase 1b) and overall response rate (ORR) (phase 2); secondary endpoints were pharmacokinetics, duration of response (DoR), time to response, progression free survival and overall survival. Responses were assessed using Lugano 2014 response criteria beginning at week 8. Results: As of 18 June 2021, 55 patients were enrolled (phase 1b: 25; phase 2: 30). Lymphoma subtypes were DLBCL (n=7), extranodal NK/T-cell (ENKTL) (n=9), PTCL, not otherwise specified (PTCL-NOS) (n=5), angioimmunoblastic T cell lymphoma (n=6), cutaneous T cell (n=1), HL (n=11), other B cell (n=3), and immunodeficiency-associated lymphoproliferative disorders (IA-LPD) (n=13), including PTLD (n=4), HIV-associated (n=5), and other [n=4: systemic lupus erythematosus (SLE) (n=2), common variable/primary immunodeficiency (n=2)]. Median age was 60 years (range 19-84), M/F 35/20, median number of prior therapies was 2 (range 1-11), 76% had ≥2 prior therapies, 78% were refractory to their most recent prior therapy, and 84% had exhausted standard therapies. EBER positivity ranged from &lt;1 to 90% in 42 tumor biopsies with central lab review. The most common treatment-emergent adverse events (TEAEs) of all grades were nausea (38%), neutropenia (34%), thrombocytopenia (34%), and constipation (31%). Grade 3/4 TEAEs in &gt;10% of patients included neutropenia (27%), thrombocytopenia (20%), anemia (20%), and lymphopenia (14%). Dose reductions and interruptions due to treatment-related AEs were reported in 14 (25%) and 16 (29%) patients, respectively. Only 1 patient had to discontinue therapy. There were no cases of CMV reactivation. For 43 evaluable patients (EBER-ISH + with ≥ 1 post-treatment response assessment) across all histologies, the investigator-assessed ORR and complete response (CR) rates were 40% (17/43) and 19% (8/43) respectively. Patients with T/NK-NHL (n=15; all refractory to their last therapy) had an ORR of 60% (n=9) with 27% (n=4) CRs. Two patients (ENKTL and PTCL-NOS) in PR and CR respectively were withdrawn at 6.7 and 6.6 months (m) respectively for autologous stem cell transplantation. For DLBCL (n=6), ORR/CR was 67%/33% (both CRs were in patients refractory to first-line R-CHOP). For IA-LPD (n=13), ORR/CR was 30%/20% (PTLD: 1 CR, other: 1 CR, 1 PR). For HL (n=10), there was 1 PR (4 SD). The median DoR for all responders was 10.4 m, with a median follow-up from response of 5.7 m (range 1.9-34.1 m). For the 17 responders, 8 lasted ≥ 6 months. Conclusions: The combination of Nstat and VGCV was well-tolerated with a manageable toxicity profile and shows promising efficacy in patients with R/R EBV + lymphomas, particularly in refractory T/NK-NHL, a heterogeneous group of aggressive lymphomas with dismal outcomes, with multiple durable responses. Further evaluation of this novel combination therapy for the treatment of recurrent EBV + lymphomas is ongoing in the phase 2 VT3996-202 trial. Disclosures Haverkos: Viracta Therapeutics, Inc.: Honoraria, Research Funding. Baiocchi: Prelude Therapeutics: Consultancy; viracta: Consultancy, Current holder of stock options in a privately-held company; Codiak Biosciences: Research Funding; Atara Biotherapeutics: Consultancy. Brammer: Seattle Genetics: Speakers Bureau; Celgene: Research Funding; Kymera Therapeutics: Consultancy. Feldman: Alexion, AstraZeneca Rare Disease: Honoraria, Other: Study investigator. Brem: Karyopharm: Membership on an entity's Board of Directors or advisory committees; SeaGen: Speakers Bureau; BeiGene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; KiTE Pharma: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Morphosys/Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Scheinberg: Roche: Consultancy; Abbvie: Consultancy; BioCryst Pharmaceuticals: Consultancy; Alexion pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau. Joffe: AstraZeneca: Consultancy; Epizyme: Consultancy. Katkov: Viracta Therapeutics, Inc.: Current Employment. McRae: Viracta Therapeutics, Inc.: Current Employment. Royston: Viracta Therapeutics, Inc.: Current Employment. Rojkjaer: Viracta Therapeutics, Inc.: Current Employment. Porcu: Viracta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Daiichi: Honoraria, Research Funding; Kiowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Spectrum: Consultancy; DrenBio: Consultancy.

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