Trial-in-Progress: Frontline Brentuximab Vedotin and CHP (A+CHP) in Patients with Peripheral T-Cell Lymphoma with Less Than 10% CD30 Expression

Background In the ECHELON-2 phase 3 clinical trial, brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) showed clinically meaningful and statistically significant efficacy in patients with peripheral T-cell lymphoma (PTCL) across a range of CD30 expression levels, including the lowest eligible level of 10% by IHC. In addition to the ECHELON-2 study, response data are available from an additional 344 subjects with CD30-expressing PTCL and other large-cell lymphomas (including angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma-NOS) who had been treated in studies with brentuximab vedotin as a single agent or in combination with chemotherapy, in both frontline and relapsed/refractory settings. Among these 344 subjects, 184 had tumors with CD30 expression <10% by local assessment, including 83/184 with undetectable CD30 by immunohistochemistry (CD30=0). Responses to brentuximab vedotin have been observed at all levels of CD30 expression, including in tumors with undetectable CD30 levels (Advani 2019; Horwitz 2019). It is hypothesized that A+CHP will demonstrate efficacy in subjects with PTCL and CD30 expression <10% because: i) brentuximab vedotin has shown activity in lymphomas with low CD30 expression; and ii) the activity of CHP chemotherapy in PTCL is unrelated to CD30 expression. This study will include subjects with PTCL subtypes other than systemic anaplastic large cell lymphoma (sALCL). Study Design and Methods This is a dual-cohort, open-label, multicenter, phase 2 clinical trial designed to evaluate the efficacy and safety of A+CHP in subjects with non-sALCL PTCL and CD30 expression <10% on tumor cells. Enrollment will be based on CD30 expression per local lab assessment. Subjects will be assigned to 1 of 2 cohorts based on CD30 expression; up to approximately 40 subjects will be enrolled in the CD30 negative (expression <1%) cohort and approximately 40 subjects will be enrolled in the CD30 positive (expression ≥1% to <10%) cohort. An archived tumor biopsy specimen will be submitted to a central pathology lab for confirmation of CD30 expression. Only subjects with CD30 expression <10% per central confirmation will be analyzed for the primary and secondary endpoints. Subjects will receive 21-day cycles of A+CHP for a target of 6-8 cycles. The primary endpoint of this trial is objective response rate (ORR) per blinded independent central review (BICR). Key secondary endpoints include CR and PFS per BICR and overall survival. Key inclusion criteria include the following: subjects aged 18 years and older with newly diagnosed PTCL, excluding sALCL, per the WHO 2016 classification; CD30 expression <10% by local assessment; and fluorodeoxyglucose-avid disease by PET and measurable disease of at least 1.5 cm by CT, as assessed by the site radiologist. Lymphoma response and progression will be assessed by BICR using Revised Response Criteria for Malignant Lymphoma and modified Lugano criteria. A CT scan will be performed at the time of suspected clinical progression. Subsequent restage assessments (CT scans only) will be performed according to the calendar, relative to the first dose of study treatment, to ensure that tumor progression is uniformly assessed between the treatment arms. Efficacy and safety endpoints will be summarized with descriptive statistics by cohort, with the CD30 negative cohort and the CD30 positive cohort. The summary of overall (CD30 negative and positive cohort combined) may be presented as appropriate. Descriptive statistics (mean, median, standard deviation, minimum, and maximum) will be used to describe continuous variables. Time-to-event endpoints, such as PFS, will be estimated using Kaplan-Meier methodology and Kaplan-Meier plots will be presented. Medians for time-to-event analyses (eg, median PFS), will be presented and two-sided 95% confidence intervals will be calculated using the log-log transformation method. The trial will have sites open in the US and multiple countries in Europe, with enrollment planning to begin in September 2020. Disclosures Jagadeesh: Verastem: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; MEI Pharma: Research Funding; Debiopharm Group: Research Funding; Regeneron: Research Funding. Sims:Seattle Genetics, Inc.: Current Employment, Current equity holder in publicly-traded company, Other: Travel expenses. Horwitz:ASTEX: Consultancy; Millenium/Takeda: Consultancy, Research Funding; Corvus: Consultancy; Innate Pharma: Consultancy; Mundipharma: Consultancy; Seattle Genetics: Consultancy, Research Funding; Trillium: Consultancy, Research Funding; Forty Seven: Consultancy, Research Funding; Infinity/Verastem: Research Funding; Celgene: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Aileron: Consultancy, Research Funding; ADCT Therapeutics: Consultancy, Research Funding; Janssen: Consultancy; Myeloid Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Vividion Therapeutics: Consultancy; Affirmed: Consultancy; Kura Oncology: Consultancy; Miragen: Consultancy; Kyowa Hakka Kirin: Consultancy, Research Funding; Beigene: Consultancy; C4 Therapeutics: Consultancy; Daiichi Sankyo: Research Funding; Portola: Consultancy, Research Funding.

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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 ◽

10.1182/blood-2021-151645 ◽

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 <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 (<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 <10% on tumor cells. Up to approximately 40 patients will be enrolled in each of the CD30-negative (expression <1%) and the CD30-low (expression ≥1% to <10%) cohorts. Patients will be enrolled based on local results but only patients with CD30 expression <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 <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.

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

Blood ◽

10.1182/blood.v120.21.1614.1614 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1614-1614 ◽

Cited By ~ 5

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.

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

Blood ◽

10.1182/blood.v128.22.3000.3000 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3000-3000 ◽

Cited By ~ 1

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.

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Outcome of Patients with Peripheral T-Cell Lymphoma Undergoing Allogeneic Stem Cell in British Columbia

Blood ◽

10.1182/blood.v128.22.5852.5852 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5852-5852

Author(s):

Musa Alzahrani ◽

Kerry J Savage ◽

Cynthia L. Toze ◽

Laurie H Sehn ◽

Raewyn Broady ◽

...

Keyword(s):

British Columbia ◽

T Cell ◽

Research Funding ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Primary Therapy ◽

Peripheral T Cell Lymphoma ◽

Free Survival ◽

Kaplan Meier

Abstract Background: Peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous group of non-Hodgkin lymphomas (NHLs) that accounts for approximately 10% of all aggressive NHLs in Western countries. The optimal management remains unclear, however, given the poor outcome, allogeneic transplant (allo-SCT) has been integrated into the front-line treatment for some rare extranodal subtypes as well in relapsed/refractory setting. We report our provincial experience of the outcome of patients with PTCL who have undergone allo-SCT at the British Columbia Cancer Agency (BCCA). Methods: The Leukemia/BMT Program of British Columbia database and the BCCA Lymphoid Cancer Database were searched to identify all patients diagnosed with PTCL who have undergone allo-SCT between November 1990 and January 2016. Overall survival and relapse free survival were estimated using the Kaplan-Meier method. Results: We identified 36 cases of PTCL patients who have undergone allogeneic transplant from a median time of 11 months from primary diagnosis (range 4-64) with the following clinical features: median age at transplant was 45 years (range 16-58 years); 24 (67%) were male; 32 (89%) patients had advanced stage disease; 22 (61%) had B-symptoms at diagnosis. Bone marrow involvement detected in 13/34 (38%) patients. Histological diagnosis based on the WHO 2008 classification were: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) n=15 (42%); anaplastic large cell lymphoma (ALCL) n=7 (19%) out of which three were ALK positive, angioimmunoblastic T-cell lymphoma (AITL) n=6 (17%), hepatosplenic T-cell lymphoma n=5 (14%), enteropathy associated T-cell lymphoma type I n=1, advanced primary cutaneous gamma-delta T-cell lymphoma n=1 and Sezary syndrome n=1. Ten patients (28%) underwent allo-SCT as part of planned primary therapy after achieving their first remission [6 were in complete remission 1 (CR1) and 4 were in partial remission 1 (PR1)], whereas 26 patients (72%) underwent allo-SCT for relapsed/refractory disease. CHOP was administered in 19 patients (53%) as the primary therapy. 17 (47%) patients received alternative chemotherapy regimen due to patient and/or physician preference. The clinical status at the time of transplantation was CR in 12 patients (33%), relapsed sensitive disease n=10 (28%), relapsed untreated n=5 (14%), partial remission (PR) in 5 (14%), primary progressive disease n=3 (8%) and relapsed resistant disease n=1 (3%). Thirty two patients (89%) underwent myeloablative conditioning, 4 (11%) underwent reduced intensity conditioning (RIC). The conditioning regimens included: cyclophosphamide/TBI n=24 (67%), busulfan/cyclophosphamide n=5 (14%), fludarabine containing reduced intensity n=4 (11%), and other regimens n= 3 (8%). With a median follow-up of alive patients from the time of allo-SCT of 69 months (range 1-186 months). At last follow-up, 17 (47%) patients have died, 6 from disease relapse, 5 from graft vs host disease (GVHD), 2 from regimen related toxicity and 4 from other causes. Nineteen patients (53%) still alive at last follow up post-transplant of which 14 (39%) still in remission. The 5-year event free survival (EFS) and overall survival (OS) from the time of allo-SCT of all patients were 43% and 63%, respectively. For PTCL-NOS the 5-year EFS and OS were 52% and 69%, respectively. Table 1 summarizes the patients' characteristics. Figures 1 and 2 shows the Kaplan-Meier curves for OS and EFS respectively. Conclusion: Allo-SCT can be effective strategy in select patients with relapsed/refractory PTCL and those with high risk histologies in the upfront setting PTCL with an acceptable toxicity. Disclosures Toze: Roche Canada: Research Funding. Sehn:roche/genentech: Consultancy, Honoraria; amgen: Consultancy, Honoraria; seattle genetics: Consultancy, Honoraria; abbvie: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; celgene: Consultancy, Honoraria; lundbeck: Consultancy, Honoraria; janssen: Consultancy, Honoraria. Scott:NanoString Technologies: Patents & Royalties: named inventor on a patent for molecular subtyping of DLBCL that has been licensed to NanoString Technologies. Villa:Lundbeck: Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria. Connors:NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Bristol Myers Squib: Research Funding; Seattle Genetics: Research Funding; Millennium Takeda: Research Funding. Song:Janssen: Honoraria; Otsuka: Honoraria; Celgene: Honoraria, Research Funding.

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Brentuximab Vedotin (BV) and Lenalidomide (Len) in Relapsed and Refractory (r/r) Cutaneous (CTCL) and Peripheral (PTCL) T-Cell Lymphomas; A Planned Interim Analysis of Phase II Trial

Blood ◽

10.1182/blood-2019-123801 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2853-2853

Author(s):

Basem M. William ◽

Ying Huang ◽

Amy Johnson ◽

Jonathan E Brammer ◽

John C. Reneau ◽

...

Keyword(s):

T Cell ◽

Board Of Directors ◽

Phase Ii ◽

Research Funding ◽

Cell Lymphoma ◽

Single Agent ◽

Large Cell ◽

Median Number ◽

Brentuximab Vedotin ◽

Advisory Committees

Background: Patients with r/r tumor stage CTCL and/or PTCL have a poor prognosis. BV is currently FDA approved for CD30 positive CTCL and anaplastic large cell lymphoma (ALCL) with single agent activity in additional PTCL subtypes. Len also has single agent activity in patients with r/r CTCL/PTCL. The safety of the combination was established in a phase I trial in patients with r/r diffuse large B-cell lymphoma. Methods: We conducted a single-institution phase II trial to determine the safety and efficacy of BV+Len combination in patients with r/r CTCL/PTCL. Simon's 2-stage optimal design was followed to test the null hypothesis of overall response rate (ORR) ≤0.3 versus the alternative hypothesis of ORR≥0.5. Patients with ≥ 1 line of systemic therapy or 2 lines of skin directed therapy, at least stage IB (for CTCL), and no prior progression on BV were eligible regardless of CD30 staining. All patients were treated with BV 1.2 mg/kg IV and Len 20 mg PO daily q3 weeks for a maximum 16 cycles. After 7 patients were treated, we reduced Len to 10 mg given safety/tolerability concerns. Responses are assessed by the International Society for Cutaneous Lymphomas and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (ISCL/EORTC) Global response criteria (for CTCL) and Cheson year criteria (for PTCL). The effect of treatment on quality of life is assessed by Skindex-16. Results: As of July 1, 2019, 17 subjects were treated; 10 (59%) with mycosis fungoides (MF), 2 (12%) with Sezary syndrome (SS), 2 (12%) with CD30+ lymphoproliferative disorder, and 3 (18%) with PTCL. Median age was 60 (49-90) years and 76% were males. CD30 was completely negative (<1%) in 3 (18%) of patients and median CD30 staining (by immunohistochemistry) was 7.5% (range 1-75%). Of 12 patients with MF/SS, 5 (42%) had evidence of large cell transformation at accrual. Of 14 patients with CTCL, median baseline mSWAT was 54.5 (range 4.4-190). Median number of prior therapies was 5 (range 1-9). Grade 3 adverse events (AEs) were reported in 11/17 patients; including neutropenia (4), thrombocytopenia (1), bronchitis (1), dyspnea (1), abdominal pain (2), vertigo (1), , DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome (1), urinary tract infection (1), and tumor flare (2). Median number of cycles received was 4 (range 1-17). Best response in 14 evaluable patients were 2 (14%) complete response, 3 (21%) partial response, and 8 (57%) stable disease with ORR of 33% (95% confidence interval:12-62%). Of 17 patients, 5 (29%) remain on treatment, and 12 (71%) discontinued treatment because of disease progression (7; 58%), AEs (4; 33%), or patient preference (1; 2%). Median duration of response was 3.2 (range 2.5-13) months. Of note, 7/14 patients (50%) patients with CTCL had >50% reduction in their Skindex-16 scores after a median of 2 cycles (range 1-3). Conclusions: BV + Len is combination is safe and efficacious in a heavily pre-treated patients with T-cell lymphomas. Len doses higher than 10 mg daily are poorly tolerated and associated with excess tumor flare. Recruitment of both CTCL and PTCL patients for this trial is ongoing. Disclosures William: Guidepoint Global: Consultancy; Kyowa Kirin, Inc.: Consultancy; Defined Health: Consultancy; Techspert: Consultancy; Celgene Corporation: Consultancy. Brammer:Verastem, Inc: Research Funding; Viracta Therapeutics, Inc.: Research Funding; Bioniz Therapeutics, Inc.: Research Funding. Grantier:Pharmacyclics LLC and Janssen Oncology: Other: Advisory Board. Hoffman:Pharmacyclics LLC and Janssen Oncology: Other: Advisory Board. Baiocchi:Prelude: Consultancy. Epperla:Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Christian:Triphase: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Immunomedics: Research Funding; Acerta: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Cephalon: Research Funding; Merck: Research Funding; Janssen: Research Funding; Millennium Pharmaceuticals Inc: Research Funding. Maddocks:BMS: Research Funding; Merck: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Brentuximab vedotin is being used off-label for CD30 negative peripheral and cutaneous T-cell lymphoma. Lenalidomide is being used off-label for both conditions (within a phase II clinical trial)

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Analysis of Patients with Common Peripheral T-Cell Lymphoma Subtypes From a Phase 2 Study of Romidepsin in Relapsed or Refractory Peripheral T-Cell Lymphoma

Blood ◽

10.1182/blood.v118.21.591.591 ◽

2011 ◽

Vol 118 (21) ◽

pp. 591-591 ◽

Cited By ~ 1

Author(s):

Bertrand Coiffier ◽

Barbara Pro ◽

H. Miles Prince ◽

Francine M. Foss ◽

Lubomir Sokol ◽

...

Keyword(s):

T Cell ◽

Research Funding ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Employment Equity ◽

Peripheral T Cell Lymphoma ◽

Advisory Committees ◽

Equity Ownership ◽

Prior Systemic Therapy ◽

Grade 3

Abstract Abstract 591FN2 Background: Romidepsin is a potent class 1 selective histone deacetylase inhibitor approved by the US Food and Drug Administration for treatment of patients with cutaneous T-cell lymphoma who have received at least 1 prior systemic therapy and patients with peripheral T-cell lymphoma (PTCL) who have received at least 1 prior therapy. Approval for use in patients with PTCL was based in part on results from the phase 2, single-arm, open-label registration study GPI-06-0002, which demonstrated clinical benefit and tolerability of romidepsin in patients with recurrent or refractory PTCL. The aim of this subanalysis was to evaluate the efficacy and safety of romidepsin on GPI-06-0002 in the three major subtypes of PTCL: PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase-1–negative anaplastic large cell lymphoma (ALK-1–negative ALCL). Methods: Patients with histologically confirmed PTCL who failed or were refractory to ≥ 1 prior systemic therapy received romidepsin 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days for up to 6 cycles; treatment could be extended for patients achieving stable disease (SD) or better. The primary efficacy endpoint was rate of confirmed/unconfirmed complete response (CR/CRu); secondary endpoints were objective response rate (ORR: CR/CRu + partial response [PR]) and duration of response (DOR). Because of the aggressive nature of PTCL, prolonged disease stabilization can provide patient benefit, thus ORR + SD ≥ 90 days was used as an overall measure of disease control. Efficacy assessments were made by an Independent Review Committee (IRC) and consisted of an initial radiographic review of images (CT, MRI) followed by an overall clinical assessment based on the radiology evaluations, photographs, and relevant clinical parameters. Results: Of the 131 enrolled patients, 130 patients had histologically confirmed PTCL by central review, with a median of 2 (range 1–8) prior systemic therapies for PTCL. The majority of patients (117/130) had PTCL-NOS (n = 69), AITL (n = 27), or ALK-1–negative ALCL (n = 21). Responses assessed by the IRC and the most common grade ≥ 3 adverse events (AEs) for the 3 major subtypes are noted in the table. ORR was similar across subtypes, including 30% in patients with AITL, with 19% CR/CRu. With a median duration of follow-up of 10.9 months, the median DOR for all responders was 17 months for patients with PTCL-NOS and 12 months for patients with ALK-1–negative ALCL. Median DOR was not yet evaluable for patients with AITL, who had the longest DOR ongoing at 34 months. Overall, 66% of patients experienced at least 1 grade ≥ 3 AE; 78% in patients with AITL, 67% in patients with PTCL-NOS, and 48% in patients with ALK-1–negative AITL. Eighteen of 117 patients (15%) experienced grade ≥ 3 infection; however infections led to discontinuation in only 4 of 117 patients (3%), 1 with PTCL-NOS and 3 with ALK-1–negative ALCL. Infection rates were higher in patients whose disease had bone marrow involvement or who had received prior monoclonal antibody therapy. Conclusions: Similar CR/CRu rates were observed across the 3 major PTCL subtypes (PTCL-NOS, AITL, and ALK-1–negative ALCL). Romidepsin induced durable responses in patients with the major subtypes of PTCL, with nearly half (46%) of these patients experiencing disease control. These data support the use of single-agent romidepsin to treat relapsed or refractory PTCL-NOS, AITL, and ALK-1–negative ALCL as well as the development of romidepsin-based combination regimens and front-line therapies in these histologies Disclosures: Coiffier: Celgene: Consultancy; Gloucester: Consultancy. Pro:Celgene: Consultancy, Honoraria. Prince:Celgene: Honoraria, Research Funding. Foss:Celgene: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Consultancy. Sokol:Celgene: Consultancy, Speakers Bureau; Gloucester: Research Funding. Caballero:Celgene: Speakers Bureau; Roche: Speakers Bureau; Mundipharma: Speakers Bureau; Pfizer: Speakers Bureau. Morschhauser:Bayer: Honoraria; Roche: Consultancy, Honoraria. Pinter-Brown:Celgene: Consultancy; Allos: Consultancy; Merck: Consultancy; Spectrum: Honoraria; Genetech: Speakers Bureau. Padmanabhan:Celgene: Consultancy, Honoraria. Shustov:Celgene: Research Funding, Speakers Bureau. Nichols:Celgene: Employment, Equity Ownership. Carroll:Celgene: Employment, Equity Ownership. Balser:Celgene: Contracted Consultancy. Horwitz:Celgene: Consultancy, Research Funding; Allos: Consultancy, Research Funding; Seattle Genetics: Consultancy; Novartis: Consultancy; Merck: Honoraria; Millennium: Consultancy; Genzyme: Research Funding.

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Special Drug Use Surveillance for Brentuximab Vedotin Intravenous Infusion "Relapsed or Refractory CD30-positive Peripheral T Cell Lymphoma or Pediatric Hodgkin Lymphoma"

Case Medical Research ◽

10.31525/ct1-nct04213209 ◽

2019 ◽

Author(s):

Keyword(s):

T Cell ◽

Drug Use ◽

Hodgkin Lymphoma ◽

Intravenous Infusion ◽

Cell Lymphoma ◽

Brentuximab Vedotin ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

Pediatric Hodgkin Lymphoma

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Peripheral T-cell lymphomas unspecified presenting in the skin: analysis of prognostic factors in a group of 82 patients

Blood ◽

10.1182/blood-2002-07-1960 ◽

2003 ◽

Vol 102 (6) ◽

pp. 2213-2219 ◽

Cited By ~ 161

Author(s):

Marcel W. Bekkenk ◽

Maarten H. Vermeer ◽

Patty M. Jansen ◽

Ariënne M. W. van Marion ◽

Marijke R. Canninga-van Dijk ◽

...

Keyword(s):

T Cell ◽

Cell Size ◽

Cell Lymphoma ◽

Large Cell ◽

Skin Lesions ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

T Cell Lymphomas ◽

Nor Phenotype ◽

Peripheral T Cell Lymphomas

Abstract In the present study the clinicopathologic and immunophenotypic features of 82 patients with a CD30– peripheral T-cell lymphoma, unspecified, presenting in the skin were evaluated. The purpose of this study was to find out whether subdivision of these lymphomas on the basis of cell size, phenotype, or presentation with only skin lesions is clinically relevant. The study group included 46 primary cutaneous CD30– large cell lymphomas and 17 small/medium-sized T-cell lymphomas as well as 17 peripheral T-cell lymphomas with both skin and extracutaneous disease at the time of diagnosis. Patients with primary cutaneous small- or medium-sized T-cell lymphomas had a significantly better prognosis (5-year-overall survival, 45%) than patients with primary cutaneous CD30– large T-cell lymphomas (12%) and patients presenting with concurrent extracutaneous disease (12%). The favorable prognosis in this group with primary cutaneous small- or medium-sized T-cell lymphomas was particularly found in patients presenting with localized skin lesions expressing a CD3+CD4+CD8– phenotype. In the primary cutaneous T-cell lymphoma (CTCL) group and in the concurrent group, neither extent of skin lesions nor phenotype had any effect on survival. Our results indicate that peripheral T-cell lymphomas, unspecified, presenting in the skin have an unfavorable prognosis, irrespective of the presence or absence of extracutaneous disease at the time of diagnosis, cell size, and expression of a CD4+ or CD8+ phenotype. The only exception was a group of primary cutaneous small- or medium-sized pleomorphic CTCLs with a CD3+CD4+CD8– phenotype and presenting with localized skin lesions.

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