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

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

Frontline brentuximab vedotin in Hodgkin lymphoma and CD30-expressing peripheral T-cell lymphoma for older patients and those with comorbidities.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS8069-TPS8069
Author(s):  
Christopher A. Yasenchak ◽  
Rodolfo Eduardo Bordoni ◽  
Victor Y. Yazbeck ◽  
Dipti Patel-Donnelly ◽  
Tim Larson ◽  
...  
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
Hodgkin Lymphoma ◽  
Older Patients ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Younger Patients

TPS8069 Background: Older patients and those with significant comorbidities have not attained outcomes seen in younger patients with classical Hodgkin lymphoma (cHL) and CD30-expressing peripheral T-cell lymphoma (PTCL). Five-year progression-free survival (PFS) was 30%–45% in older HL patients treated with combination chemotherapy versus 75%–80% in younger patients (Evens 2008; Proctor 2009). Similarly, when adjusted for age, a Charleston Comorbidity Index ≥2 was independently associated with worse overall survival (HR=1.63) and PFS (HR=1.54) (Ellin 2018). Brentuximab vedotin (BV, ADCETRIS), a CD30-directed antibody-drug conjugate, has robust activity in cHL patients refractory to several lines of chemotherapy. BV monotherapy in 27 cHL patients aged ≥60 years had a 92% objective response rate (ORR) and 73% achieved complete remission (Forero-Torres, 2015). BV was also active and well-tolerated in CD30-expressing PTCL patients with relapsed or refractory disease (Horwitz 2014). Frontline BV monotherapy may have the potential to be an active and well-tolerated treatment for cHL and PTCL patients who are older or have significant comorbidities, which are populations with high unmet need. Methods: This phase II, open-label study, SGN35-015 (NCT01716806), has added 2 cohorts to evaluate the efficacy and tolerability of BV monotherapy in treatment naive patients with cHL, (Part E), or CD30-expressing PTCL (Part F, n~50 each) who are unsuitable for conventional combination therapy due to comorbidity-related factors as determined by a Cumulative Illness Rating Scale (CIRS) score ≥10 or dependence on others for any instrumental activities of daily living. Eligible patients must also have an Eastern Cooperative Oncology Group (ECOG) performance status ≤3 and measurable disease ≥1.5 cm per radiographic techniques. BV (1.8 mg/kg) will be administered as a single intravenous infusion on day 1 of each 2-day cycle. Patients achieving a complete remission, partial remission, or stable disease will receive up to 16 cycles of treatment. Response will be assessed by blinded independent central review of spiral CT and PET scans at Cycles 2, 6, 11, and at end of treatment to be graded per Lugano 2014. The primary objective of these cohorts is to assess ORR of frontline therapy with single-agent BV in patients who have significant comorbidities. Clinical trial information: NCT01716806 .

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

Brentuximab Vedotin Followed By Allogeneic Stem-Cell Transplantation for Patients with CD30 Anaplastic or T Cell Non Hodgkin Lymphomas: A Study on Behalf of the SFGM-TC.

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4377-4377
Author(s):  
Sylvain Garciaz ◽  
Michael Loschi ◽  
Adele de Masson ◽  
Sylvie François ◽  
Cecile Tomowiak ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
T Cell ◽  
Cell Lymphoma ◽  
Chronic Gvhd ◽  
Immunosuppressive Agents ◽  
Brentuximab Vedotin ◽  
Salvage Treatment ◽  
T Cell Lymphoma ◽  
Control Group ◽  
Peripheral T Cell Lymphoma

Abstract Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, has demonstrated efficacy alone or in combination with chemotherapy in CD30 refractory Non-Hodgkin Lymphoma (NHL). It has been approved in anaplastic large cell lymphoma (ALCL) and promising results have also been published in other CD30 positive T-cell lymphomas such as cutaneous T-cell lymphoma (CTCL) or peripheral T-cell lymphoma (PTCL). In patients with relapsing or refractory NHL, BV has mainly been proposed as a bridge for autologous or allogeneic transplantation (Allo-HSCT). Very few data are available about patients with T-cell NHL receiving Allo-HSCT after BV. The aim of our study was to study safety and efficacy of this procedure in a retrospective series of patients treated on behalf of SFGM-TC. Inclusion criteria were: - CD30 positive T cell NHL including ALCL, CTCL and PTCL, - Partial or Complete response after BV treatment, - Allogeneic HSCT performed after BV as last salvage treatment. BV was administered at 1,8mg/kg dose every 3 weeks in outpatient department. Allo-HSCT was performed according to institutional guidelines. Twenty-six patients receiving Allo-HSCT in France after salvage therapy including BV were identified. Patients characteristic are summarized in Table 1. With a median follow-up of 13 months (1.5-40), 8 patients relapsed and 7 patients died. Two-year OS and PFS were respectively 76% and 47%. Among patients with ALCL (n=15) 2 patients relapsed and 2 patients died. Whereas in the CTCL group (n=5), 5 patients relapsed and 1 patient died and in the PTCL group (n=6), 1 patient relapsed and 4 patients died. Two-year OS were 93%, 80% and 21% (p<0.001) and two-year PFS were 86%, 20% and 0% (p<0.001) for ALCL, CTCL and PTCL respectively. Two-years PFS for patients in CR before Allo-HSCT (n=16) was 67% whereas patients in PR (n=6) or who progressed before transplantation (n=3) have a 25% and 0% 2-years PFS respectively (p=0,08). In multivariate analysis, only anaplastic histology had a positive impact on OS or PFS. We compared data with a control group of patients with T-cell NHL (n=52) transplanted in the same centers during the same period, not receiving BV as a salvage treatment. Day-100 cumulative incidence of acute Grade 2-4 GVHD and Grade 3-4 GVHD were 39% [20-59] and 16% [1-30] in the BV group and 46% [27-66] and 19% [8-30] in the control group (p=NS). Two-years overall chronic GVHD and extensive chronic GVHD were 33% [9-56] and 22% [0-46] in the BV group and 39% [24-53] and 15% [0-26] in the control group (p=NS). Day-100 and 1-year NRM were 12% [0-25] and 16% [1-30] in the BV group and 4% [0-9] and 8% [1-15] in the control group (p=0,07). One-year relapse incidence was 37% [14-60] and 22% [10-34] in the BV and control groups respectively (p=0,27). BV was not associated with higher GVH, NRM or relapse incidence in multivariate analysis. In conclusion, BV followed by Allo-HSCT is an option for patients with advanced CD 30 positive T cell NHL. Immunotherapy targeting CD30 before Allo-HSCT is not associated with a higher rate of GVHD, NRM or relapse incidence. Patients with ALCL have a better survival than patients with PTCL or CTCL. Table 1. Patients characteristics All patients ALCL CTCL PTCL (n=26) (n=15) (n=5) (n=6) Sexe male 15 (58%) 7 (47%) 4 (80%) 4 (67%) Age (at Allo-HSCT) median (range) 47 (21-62) 40 (21-59) 50 (31-62) 50 (46-59) Stade (at diagnosis) I-II 4 (15%) 3 (20%) - 1 (17%) III-IV 16 (62%) 11 (73%) - 5 (83%) unknown 1 (4%) 1 (7%) - - NA 5 (19%) - 5 (100%) - Auto-HSCT (before BV) patients 8 (31%) 5 (33%) - 3 (50%) Lines of chemotherapy (before BV) median (ranges) 2 (1-7) 2 (1-4) 4 (3-7) 2 (1-3) Status (before BV) refractory 18 (69%) 9 (60%) 5 (100%) 4 (66%) relapsing 8 (31%) 6 (40%) - 2 (34%) cycles of BV median (ranges) 4 (1-8) 4 (1-8) 4 (4-6) 4 (1-4) Treatment associated with BV no 20 (77%) 11 (73%) 5 (100%) 4 (66%) GVD 2 (8%) 2 (13%) - - CHP 2 (8%) - - 2 (33%) DHAP 1 (4%) 1 (7%) - - Radiotherapy 1 (4%) 1 (7%) - - Time between diagnosis and Allo-HSCT Months (range) 21 (6-93) 13 (6-93) 23 (21-43) 23 (12-76) Status before Allo-HSCT CR 16 (62%) 13 (87%) - 3 (50%) PR 6 (23%) 2 (13%) 4 (80%) - SD/PD 3 (12%) - 1 (20%) 2 (33%) Donor type MRD 15 (57%) 5 (33%) 4 (80%) 6 (100%) MUD 7 (27%) 6 (40%) 1 (20%) - CBU 2 (8%) 2 (13%) - - Haploidentical 2 (8%) 2 (13%) - - Conditioning 3 (50%) RIC 17 (65%) 9 (60%) 5 (100%) MAC 9 (35%) 6 (40%) - 3 (50%) Immunosuppressive agents CyA 5 (19%) 4 (27%) - 1 (17%) CyA/MMF 10 (38%) 4 (27%) 5 (100%) 1 (17%) CyA/MTX 11 (42%) 7 (47%) - 4 (66%) Anti-thymocyte globulin 11 (42%) 8 (53%) 1 (20%) 2 (33%) Disclosures Off Label Use: Brentuximab used for CD30+ cutaneous and peripheral T cell lymphoma.

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 A Successful Experience with Brentuximab Vedotin in Relapsing/Refractory Cutaneous T-Cell Lymphoma: Two Case Reports

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5371-5371
Author(s):  
Liliya Gorenkova ◽  
Sergey K. Kravchenko ◽  
Alla M. Kovrigina ◽  
Valery G. Savchenko
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Chemotherapeutic Agents ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Allogeneic Bone ◽  
Peripheral T Cell Lymphoma ◽  
Anaplastic Lymphoma ◽  
Frequent Relapses

Abstract Primary cutaneous T-cell lymphomas are non-Hodgkin lymphomas of the skin defined by the presence of malignant T lymphocyte clonality. Mycosis fungoides (MF) accounts for more than half of these lymphomas, while CD30+ lymphoproliferative skin diseases (primary cutaneous anaplastic lymphoma and lymphomatiod papulosis (LyP)) comprise 25% of these neoplasms, and rarely seen tumors including subtypes of primary cutaneous peripheral T cell lymphoma nonspecified (NOS). A high expression of CD30 antigen on tumor cells is detected in primary cutaneous CD30+ lymphomas and transformed MF, whereas it may be observed in other entities, but a low level. While most patients with cutaneous CD30+ lymphoproliferative disorders experience an indolent disease course with an excellent prognosis, up to 30% have progressive disease with 8% of patients succumbing to their cancer. Systemic immunomodulatory or chemotherapeutic agents are often used for patients with such advanced disease, with CD30 being an increasingly attractive therapeutic target. Herein, we report two cases of a relapsing lymphomatiod papulosis and a refractory primary cutaneous peripheral T cell lymphoma NOS. Target therapy with brentuximab vedotin either as a single agent or combined with chemotherapy resulted in a stable long-term remission. Patient 1, a man of 45 years of age, received treatment for Hodgkin lymphoma about 5 years ago. Already at that time, he noted self-regressing crops of pruritic papules or nodules on the face. In a year after chemotherapy had stopped, this skin elements recurrent with subsequent partial regression. LyP type D was identified on histological examination (picture 1). Following several lines of therapy, frequent relapses were noted and a lesser quantity of lesions tended to resolve leaving scars and hyperpigmentation. The complete remission was achieved after 6 cycles of brentuximab vedotin, at a follow-up period of 12 months no evidence of relapse were found (picture 2). Patient 2, a 30-year aged man. First solitary skin lesions occurred 2.5 years ago. The patient received combination therapy with low doses of chemotherapeutic agents and subsequently had progression of the disease. The patient received more 3 lines of high-dose chemotherapy; however, the disease was rapidly progressive with increasing size of lesions and newly appearing tumor lesions in the skin (picture 3). The remission was achieved after a combination regimen which included Dexa Beam courses and brentuximab vedotin (picture 4). The matched allogeneic bone marrow transplantation is planned for the patient to consolidate the remission. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial

The Lancet ◽  
2019 ◽  
Vol 393 (10168) ◽  
pp. 229-240 ◽  
Author(s):  
Steven Horwitz ◽  
Owen A O'Connor ◽  
Barbara Pro ◽  
Tim Illidge ◽  
Michelle Fanale ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Phase 3 ◽  
Double Blind
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