Long-Term Outcomes of Patients with Peripheral T-Cell Lymphoma after Autologous Hematopoietic Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Olivier Veilleux ◽  
Francisco Socola ◽  
Sally Arai ◽  
Robert Lowsky ◽  
Judith A Shizuru ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Study Cohort ◽  
Private Company ◽  
Autologous Transplant ◽  
Support Research

Introduction: Patients with T-cell lymphoma have variable clinical manifestations and outcomes depending on the histology and their response to therapies. However, the overall outcomes are not as good as their B-cell lymphoma counterpart with induction chemotherapy alone. Therefore, autologous transplant is often used as consolidation in first remission or at relapse because of the poor outcomes with conventional therapy. We have reported previously on Stanford experience of these patients who underwent autologous transplant before 2007 (BBMT 2008, 14:741). Here, we reported a retrospective review of patients in the modern era (2008-2018) with emphasis on the impact of pre-transplant disease status on outcomes and post-transplant relapse management. Method: Between July 1, 2008 and July 31, 2018, 102 consecutive patients with T-cell lymphoma received high dose chemotherapy/autologous hematopoietic cell rescue at Stanford and constitute the study cohort (Figure 1). This study cohort was selected for adequate follow-up (>2 years) after transplant. Progression free survival (PFS) and overall survival (OS) was estimated from the date of transplant using the Kaplan-Meier method. PFS and OS were compared between groups with different pre-transplant disease status based on response to the last pre-transplant therapies (CR1 vs. PR1 vs. CR2). Result: This study cohort included patients with peripheral T-cell lymphoma, non-specified (n=21), angioimmunoblastic T-cell lymphoma (n=50), ALK-negative anaplastic large-cell lymphoma (n=14), ALK-positive anaplastic large-cell lymphoma (n=5), extranodal NK/T cell lymphoma (n=9), enteropathy-type T-cell lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1) and hepatosplenic T-cell lymphoma (n=1). It had a male/female ratio of 61/41, and a median age of 58 years (range 23-71). At diagnosis the majority of the patients had stage III/IV disease (70%) and B symptoms (56%). The median time from diagnosis to transplant was 8.1 months (range 4-176). The majority of patients were in first complete remission (CR1, n=79) at the time of transplant, while others were in PR1 (n=11) or in CR2 (n=12) from last pre-transplant therapies. Ninety-one (89%) patients received high dose cyclophosphamide/carmustine/etoposide(CBV) and 11 patients received high dose carmustine/etoposide/cytarabine/melphalan (BEAM) prior to autograft infusion. Median follow-up post-transplant was 36.8 months (range 0.7-130) for the entire cohort. The estimated 3-year PFS and OS were 60% (95% CI 49-68%) and 75% (95% CI 65-82%), respectively (Figure 2A). Patients who were in CR1 had significantly better median PFS compared to patients in PR1 or CR2 (7.04 vs 1.19 years, p=0.039; 7.04 vs 0.48 years p=0.004, Figure 2B). The estimated 3-year PFS were 67% (95% CI 55-76%), 36% (95% CI 11-63%), and 29% (95% CI 8-56%) for the CR1, PR1 and CR2 groups respectively. Patients who were in CR1 also had significantly better median OS compared to patients in PR1 or CR2 (not reached vs 2.30 years, p=0.018; not reached vs 3.76 years p=0.045, Figure 2C).The estimated 3-year OS were 82% (95% CI 71-89%), 44% (95% CI 14-70%), and 53% (95% CI 21-78%) for the CR1, PR1 and CR2 groups respectively. In this cohort, there were no significant differences in either PFS or OS between different histology. Forty patients experienced disease relapse after transplant. The majority (n=28, 70%) of these patients received additional therapies including chemotherapy (n=13), brentuximab vedotin (n=12), HDAC inhibitor (n=7), and radiation (n=3) with a median systemic therapy of 2 (range 1-5). Thirteen patients eventually underwent allogeneic hematopoietic cell transplantation. The median OS after post-transplant relapse was 21.3 months (Figure 3). Both brentuximab vedotin and allogeneic transplant seemed to provide prolonged survival for these relapsed patients, with estimated 2-year post-relapse OS were 75% (95% CI 13-96%) and 63% (95% CI 28-84%) for the two groups respectively. Conclusion: Autologous transplant remains to be a good option as consolidation for patients with T-cell lymphoma, mostly in patients with first complete remission. While close to 40% of the patients experienced relapse after autologous transplant, additional therapies such as brentuximab vedotin or/and allogeneic transplant can provide long-term benefit for these patients. Disclosures Shizuru: Jasper Therapeutics, Inc: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Shiraz:Kite, a Gilead Company: Research Funding; ORCA BioSystems: Research Funding. Muffly:Servier: Research Funding; Amgen: Consultancy; Adaptive: Research Funding. Sidana:Janssen: Consultancy. Meyer:Orca Bio: Research Funding. Rezvani:Pharmacyclics: Research Funding. Miklos:Novartis: Consultancy, Other: Travel support, Research Funding; Pharmacyclics: Consultancy, Other: Travel support, Patents & Royalties, Research Funding; Allogene Therapeutics Inc.: Research Funding; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy, Other: Travel support; Miltenyi Biotec: Research Funding; Adaptive Biotech: Consultancy, Other: Travel support, Research Funding. Negrin:Magenta Therapeutics: Consultancy, Current equity holder in publicly-traded company; Biosource: Current equity holder in private company; Amgen: Consultancy; BioEclipse Therapeutics: Current equity holder in private company; UpToDate: Honoraria; KUUR Therapeutics: Consultancy.

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 <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.

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 T-Cell Lymphomas: Online Education Significantly Improves Clinicians' Knowledge of Therapeutic Advances

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4960-4960
Author(s):  
Elizabeth J Heller ◽  
Sarah L Williams ◽  
Keira P Smith ◽  
Steven M. Horwitz
Keyword(s):  
T Cell ◽  
Online Education ◽  
Research Funding ◽  
Clinical Decision Making ◽  
Cell Lymphoma ◽  
Clinical Decision ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
Activity Assessment ◽  
Case Based

Abstract Background: Therapeutic advances have made the treatment of T-cell lymphomas (TCLs) more effective, less toxic, and more individualized, but research indicates that the multidisciplinary team faces challenges in maintaining a working knowledge of evolving data that can inform clinical decision making. This study was conducted to determine if an online, case-based continuing medical education (CME)/nursing continuing professional development (NCPD) activity could improve clinicians' skills regarding the individualized treatment of patients with TCLs. The educational intervention was intended for all members of the multidisciplinary team: hematologist-oncologists, oncology advanced practitioners and nurses, and other health care professionals involved in the treatment of patients with TCLs. Methods: The CME/NCPD-approved live webinar series titled Update on Therapeutic Advances in T-Cell Lymphoma was presented on March 11, 2021 and March 15, 2021, and was made accessible as a CME/NCPD-approved enduring webinar archive starting on March 18, 2021. Learners participated in a 1-hour online activity regarding current challenges and emerging opportunities in the management of newly diagnosed and relapsed/refractory TCLs. The presentation highlighted mechanisms of action, efficacy, and tolerability of newer therapeutic agents, along with adverse event management strategies. Learners engaged in active learning during case studies that explored patient and disease characteristics that inform care, risk stratification, and treatment. Prior to the activity and following its completion, learners were given a repeated pairs pre- and post-activity assessment consisting of case-based questions that gauged their ability to apply emerging data and guideline recommendations to clinical decision making. Each learner served as their own control. The percentages of learners obtaining correct responses on the pre-activity assessment were compared to those on the post-activity assessment using a chi-squared test. Additionally, learners completed an evaluation of the educational content and self-reported the influence that they judged the activity would have on their future practice. Results: As of July 29, 2021, 218 clinicians had completed the activity for credit. Online education had a significant impact on gains in knowledge and competence in the selection of personalized treatment for patients with TCLs (Figure 1). Learners demonstrated substantial improvements in knowledge of the superior efficacy of mogamulizumab versus vorinostat for a patient with previously treated stage IVB mycosis fungoides (55.67% mean improvement on the post-activity assessment, P < .000001); of the association of the TET2 mutation with angioimmunoblastic T-cell lymphoma (AITL) (54.35% improvement, P < .000001); of the predicted efficacy of oral azacitidine/CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) for an older patient with peripheral T-cell lymphoma-T follicular helper (PTCL-TFH) (31.28% improvement, P < .000001); of the appropriateness of granulocyte colony-stimulating factor (G-CSF) prophylaxis for a patient with CD30-positive PTCL commencing treatment with brentuximab vedotin/CHP (cyclophosphamide/doxorubicin/prednisone) (19.90% improvement, P < .000001); and of the superior efficacy of brentuximab vedotin versus methotrexate for CD30-positive primary cutaneous anaplastic large cell lymphoma (pcALCL) (17.33% improvement, P < .000001). The case-based assessment questions and answer choices can be seen in Table 1. Learners' responses on the activity evaluation can be seen in Figures 2 and 3. Conclusions: These data indicate that online, case-based CME/NCPD-approved activities can result in statistically significant improvements in clinicians' knowledge of therapeutic advances and can increase their sense of competence and confidence in personalizing treatment plans and managing treatment-related adverse events for patients with TCLs. Acknowledgements: This activity was supported by independent educational grants from Kyowa Kirin and Seagen. Figure 1 Figure 1. Disclosures Horwitz: Affimed: Research Funding; Aileron: Research Funding; 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; 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 Central Nervous System Involvement in Peripheral T-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5293-5293
Author(s):  
Sangeetha Gandhi ◽  
N. Nora Bennani ◽  
Sonia Fortin ◽  
Thomas M. Habermann ◽  
Patrick Johnston ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Advisory Board ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Cns Involvement ◽  
Advisory Committees ◽  
Genetics Research

Background: Central nervous system (CNS) involvement by peripheral T cell lymphoma (PTCL) is a rare condition. Among primary CNS lymphomas, only 2% are secondary to PTCL, while the risk of CNS relapse in all cases of PTCL is estimated at 2% to 6%. Little is known about the presentation and outcomes of PTCL patients with CNS involvement given the rarity of this entity. In this study, we describe patient characteristics, histology, and clinical course of patients with CNS involvement by PTCL. Methods: The Mayo Clinic Lymphoma Database was used to identify PTCL patients with primary or secondary CNS involvement seen at our institution between 2000 and 2018. A total of 12 patients were identified and their medical records were reviewed for patient and disease characteristics, CNS-directed treatment modality, and outcomes. The Kaplan-Meier method was used for time-to-event analysis. Results: The median age at CNS diagnosis was 63 years (range 41 to 76) and 11 (93%) patients were male. The histological diagnoses were PTCL, NOS in 9 (75%) patients, enteropathy-associated T-cell lymphoma in 2 (17%) patients, and angioimmunoblastic T-cell lymphoma in 1 (8%) patient. Five patients presented with primary T-cell CNS lymphoma (all with a PTCL, NOS histology), while the remaining 7 (58%) patients also had systemic involvement. All patients presented with neurologic symptoms at the time of CNS involvement diagnosis including: focal motor deficits in 6 patients (unilateral upper extremity weakness, gait impairments, and hemiparesis), cognitive decline in 5 patients (memory impairments, reduced attention, and confusion), headache in 4 patients, and seizure in 3 patients. The CNS disease location included the brain parenchyma in 9 (75%) patients, leptomeninges in 1 (8%) patient, and lumbar plexus in 1 (8%) patient. One patient (8%) had positive CSF finding only without radiologic evidence of involvement. CSF analysis was performed in 11 patients. Elevated protein levels were noted in 3 (27%) patients, malignant cells in 2 (18%), and no clear abnormalities in the remaining 6 (55%) patients. Concomitant bone marrow involvement was seen in only 1 patient. Elevated LDH was seen in 2 patients. The a median LDH was 195 U/L (range 139 to 4,360) The most common CNS-directed therapies were: high-dose methotrexate (MTX)-based regimens in 8 (67%) patients, including high-dose MTX in combination with temozolomide (n=2), or cytarabine and thiotepa (n=2). Intrathecal MTX, temozolomide and dexamethasone, lenalidomide, high-dose steroids, and surgical resection were the treatment modality used for one patient each. At a median follow up of 18 months, eight (75%) out of 12 patients were not alive at the time of last follow up. The median overall survival (OS) from diagnosis was 16 months (95% CI: 2.8-173). The median progression free survival (PFS) from initiation of CNS-directed therapy was 9 months (95% CI: 1.6-33) (figure). Four patients had a PFS longer than 12 months. These 4 patients were treated with: temozolomide/dexamethasone, high-dose MTX, lenalidomide, and high-dose MTX followed by cytarabine/thiothepa. Conclusion: CNS involvement by T-cell lymphoma is a rare complication that carries a poor prognosis. Early onset of neurologic symptoms should trigger prompt investigation of CNS involvement. Despite the short OS and PFS, some patients may achieve a relatively longer disease free interval. Disclosures Bennani: Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board. Cerhan:Celgene: Research Funding; NanoString: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Nowakowski: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; NanoString: Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees. Ansell:Mayo Clinic Rochester: Employment; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding. Paludo:Celgene: Research Funding; Verily Life Sciences: Research Funding; Verily Life Sciences: Research Funding; Celgene: Research Funding.

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

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-30
Author(s):  
Deepa Jagadeesh ◽  
Robert B. Sims ◽  
Steven M. Horwitz
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Advisory Committees ◽  
Kaplan Meier ◽  
Secondary Endpoints

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.

scholarly journals Weekly Dosing Schedule of Brentuximab Vedotin in Mycosis Fungoides/Sezary Syndrome and Aggressive T Cell Lymphomas

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Megan Lee ◽  
Molly Schiffer ◽  
Iris Isufi ◽  
Scott F. Huntington ◽  
Mina L. Xu ◽  
...  
Keyword(s):  
T Cell ◽  
Clin Oncol ◽  
Mycosis Fungoides ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
Weekly Schedule ◽  
Dosing Schedule ◽  
T Cell Lymphomas

Introduction While the approved dose of brentuximab in T cell lymphomas has been every 3 weeks on a 1.8 mg/kg schedule, earlier studies exploring weekly dosing showed that a dose of 1.2 mg/kg on a weekly dosing (every 3 out of 4 weeks) in pts with Hodgkin's lymphoma and hematologic malignancies may improve cancer response rates while still having manageable side effects3. We explored the weekly dosing schedule in 37 pts (pts) with mycosis fungoides/Sezary syndrome (MF/SS) and aggressive T cell lymphomas and compared to our experience with every 3 week dosing in 36 pts to evaluate tolerability and efficacy of the weekly schedule.. Methods We reviewed charts of 67 pts, 36 received dosing q 3 weeks and 37 received a dose weekly for 3 consecutive weeks on a 4-week schedule. Pts included MF/SS (n=35), gamma delta T cell lymphoma (n=2), anaplastic large cell lymphoma (n=12), Peripheral T cell Lymphoma (n=10), angioimmunoblastic T cell lymphoma (n=4), adult T cell leukemia (n=2), and NK-T cell lymphoma. Pts were treated with brentuximab vedotin at a dose of either 1.8 mg/kg every 3 weeks or 1.2 mg/kg weekly x 3 every 4 weeks. CD30 expression was scored by the pathologist in tumor biopsies as high (<50%), low (5-10%), or intermediate (>10%-49%). Toxicity data was recorded from the medical records and data analyzed descriptively. Results Of 67 pts in this study, the average age was 61. Doses were 1.8 mg/kg for the q 3 week schedule and 0.75 to 1.2 mg/kg for the weekly x 3 schedule. Cycles were 3-47 for q 3 weeks and 1-9.7 for weekly dosing. CD30 expression was high in 13% of pts, low in 43%, and absent in 6% with equal distribution between the weekly and q 3 week cohorts, as shown in Table 1. Dose adjustments were made in 67% of q 3 week and 61% of weekly pts for neurotoxicity (n=28), with a higher incidence in the q 3 week pts compared to those with weekly dosing (75% vs 53%, p=0.01) . Discontinuation for progression (25% vs 30%) was similar for both groups. In the weekly group, 8 pts had a stem cell transplant, including allogeneic transplantation in 3. Conclusion In the Phase II registration trial of brentuximab vedotin 1.8 mg/kg q3 weeks, 41% of pts had neuropathy (severe in 12%). 1 Forty two percent of discontinuations were for neuropathy. In our weekly schedule, incidence of neuropathy was lower and led to fewer treatment discontinuations. Our retrospective data shows that Brentuximab vedotin is well tolerated on a weekly dosing schedule and has activity in pts with MF/SS and aggressive T cell lymphomas. As in prior studies, responses were seen with low CD30 expression4, 5. Prospective clinical trials with a self-reported neurotoxicity scale and quality of life instruments should be performed address the impact of more frequent, lower doses of brentuximab vedotin on patient outcomes. 1 Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T et al.J Clin Oncol 2012; 30(18): 2190-2196. doi: 10.1200/JCO.2011.38.0402 2 Prince HM, Kim YH, Horwitz SM, Dummer R, Scarisbrick J, Quaglino P et al.Lancet 2017; 390(10094): 555-566. doi: 10.1016/S0140-6736(17)31266-7 3 Fanale MA, Forero-Torres A, Rosenblatt JD, Advani RH, Franklin AR, Kennedy DA et al.Clin Cancer Res 2012; 18(1): 248-255. doi: 10.1158/1078-0432.CCR-11-1425 4 Duvic M, Tetzlaff MT, Gangar P, Clos AL, Sui D, Talpur R. J Clin Oncol 2015; 33(32): 3759-3765. doi: 10.1200/JCO.2014.60.3787 5 Kim YH, Tavallaee M, Sundram U, Salva KA, Wood GS, Li S et al.J Clin Oncol 2015; 33(32): 3750-3758. doi: 10.1200/JCO.2014.60.3969 Figure Disclosures Huntington: Pharmacyclics: Honoraria; DTRM: Research Funding; Genentech: Consultancy; Novartis: Consultancy; Celgene: Consultancy, Research Funding; TG Therapeutics: Research Funding; Bayer: Consultancy, Honoraria; AbbVie: Consultancy; Astrazeneca: Honoraria. Xu:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Phase I Study of Yttrium-90 Labeled ANTI-CD25 (aTac) Monoclonal Antibody PLUS BEAM for Autologous Hematopoietic CELL Transplantation (AHCT) in Patients with Mature T-CELL NON-Hodgkin Lymphoma, the "a-TAC-BEAM Regimen"

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 611-611 ◽  
Author(s):  
Jasmine Zain ◽  
Jennifer Simpson ◽  
Joycelynne Palmer ◽  
Jeffrey Wong ◽  
Savita Dandapani ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Cell Transplant ◽  
Yttrium 90

Abstract Background: Peripheral T cell lymphomas (PTCL) have a poor prognosis with current treatment regimens. High-dose chemotherapy followed by autologous stem cell transplant (ASCT) has been used as a consolidation strategy in remission states (CR1 or above) endorsed by the NCCN guidelines in appropriate patients. 5 year DFS is reported at 70% for alk -ve anaplastic large cell lymphoma (ALCL) and 30-40% for most other histologies (D'Amore et al, 2012, JCO). It is also performed in the relapsed settings if no previous ASCT performed and allogeneic transplant is not an option. CD25 is a targetable protein expressed differentially in PTCL and antibody based anti-CD25 therapies are efficacious in PTCL i.e denileukin diftitox (Foss et al Blood 2006, Dang et al , BJH 2006) , monoclonal antibody dacluzimab (Waldman et al 1995 Blood). Yttrium-90 (90Y) labeled chimeric antiCD25 antibody basiliximab emits beta particles and has been shown to inhibit the growth of human ALCL tumors and increase survival in SUDHL-1 xenograft mice (Zhang et al 2009 Cancer Biother Radiopharm). Previous investigations at COH by Raubitschek, Colcher et al established a safe does of Yttrium-90 (90Y) labeled basiliximab at 0.4mCi/kg in combination with BEAM. This is a phase 1 clinical trial of a novel conditioning regimen that includes the use of Yttrium-90 (90Y) labeled basiliximab with BEAM chemotherapy for PTCL patients eligible for ASCT. The trial utilizes a modified version of the rolling 6 design (Skolnik et al) to test 3 dose levels of Yttrium-90 (90Y) Basiliximab i.e 0.4mCi/kg, 0.5miC/kg and 0.6mCi/kg with the primary objective of evaluating the safety and tolerability of this combination and to establish the MTD. Secondary objectives include incidence of relapse, OS, PFS, NRM at day 100, 1 year and 2 years post-transplant. Patients and Methods: Dose limiting toxicity (DLT) is defined according to the Bearman and CTCAE 4.03 scales, the latter for hematologic toxicity. The study/treatment schema is shown in Figure 1. Results: From 07/29/2015 to 05/29/2018, 14 patients underwent ASCT on this trial; n=4 at 0.4mCi/kg n=4 at 0.5mCi/kg and n=6 at 0.6mCi/kg. Median age at ASCT was 51 years (range: 18-76), and histologies included; PTCL-nos (n=7); alk-ve ALCL (n=3); angioimmunoblastic T-cell lymphoma (n=2); and intestinal T-cell lymphoma (n=2). Disease status at ASCT were CR1 in12, CR2 in 2 patients. Median number of prior therapies was 1 (range: 1-2). At a median follow-up of 14.4 months (range: 0.9-26.2), 8 patients remain in remission, 4 have relapsed out of which 2 have died of progressive lymphoma. OS was 100% (95% CI: N/A) at 100-days, and89% (95% CI: 43-98) at 1 year. Non-relapse Mortality was 0% at both100-days and 1-year (95%CI: N/A) (95%CI: N/A). All patients successfully engrafted with the median days to ANC >= 500/ul was 11 (range: 10 - 12), and days to PLT >= 20,000/ul: 13 (12 - 92). No dose limiting toxicities were experienced. The most common/highest grade toxicity experienced (per Bearman Scale) was grade 2 stomatitis, which was seen in 3 patients at 0.4mCi/kg; 4 patients at 0.5 mCi/kg, and 3 at0.6mCi/kg. The only other toxicities seen were grade 2 GI in 2 patients at 0.4mCi/kg,and grade 2 bladder in one patient at 0.6mCi/kg dose.. Toxicities >grade 2 were not seen. Conclusion: aTac- BEAM appears to be safe as an ASCT conditioning regimen for PTCL with no increased toxicity as compared to the historical toxicities seen with BEAM alone in this patient population (D'Amore 2012 J of Clin Onc). The dose level 0.6mCi/kg will likely be the recommended phase II dose. An expanded phase is planned to evaluate the efficacy of this regimen followed by a randomized trial of BEAM alone plus a combination of aTac- BEAM. Figure 1. Figure 1. Disclosures Herrera: Seattle Genetics: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Immune Design: Research Funding; KiTE Pharma: Consultancy, Research Funding; Merck, Inc.: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Research Funding; Gilead Sciences: Research Funding. Salhotra:Kadmon Corporation, LLC: Consultancy.

scholarly journals Salvage Therapy with Brentuximab-Vedotin and Bendamustine for Patients with Relapsed/Refractory T Cell Lymphoma. a Multicenter and Retrospective Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 620-620
Author(s):  
Krimo Bouabdallah ◽  
Raphaëlle Aubrais ◽  
Loïc Chartier ◽  
Charles Herbaux ◽  
Anne Banos ◽  
...  
Keyword(s):  
Retrospective Study ◽  
T Cell ◽  
Salvage Therapy ◽  
Research Funding ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Multivariable Analysis ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity

Abstract Methods : This multicentric retrospective study aimed to evaluate the efficacy and the safety of the combination of BBV in patients with non-cutaneous R/R PTCL among 21 LYSA centers in France and Belgium. The primary objective was to evaluate the best overall response rate (ORR) (complete response (CR) and partial response (PR)). Secondary objectives were progression free survival (PFS), overall survival (OS), duration of response (DoR), impact of transplantation on outcome, and safety. Patients treated between January 2013 and October 2020 were reviewed and all the data were collected through an electronic questionnaire sent to all the physicians. Results : Eighty two patients with R/R PTCL (40 angioimmunoblastic lymphoma (AITL), 2 T-cell lymphoma with TFH phenotype ,13 PTCL not otherwise specified (PTCL NOS), 5 Alk+ anaplastic large cell lymphoma (ALCL), 17 Alk- ALCL, , 1 Extranodal NK-/T-cell lymphoma, 3 Enteropathy-associated T-cell lymphoma (EATL), 1 subcutaneous panniculitis) were included. Median age at beginning of BBV was 60 years, most of patients were male (61%), had advanced stage (88%) and an IPI ≥ 2 (79%). Half of patients were refractory to their last treatment. Median number of prior regimens was 1 (range 1 to 6). The best ORR was 71%, with 51% of patients in CR. In multivariable analysis, only the relapse status after the last regimen (relapse vs refractory) was associated with ORR, relapsed patients having a better ORR (83% vs 57% in refractory patients, p=.014, OR=3.70 (95%CI:1.3-10.5)). Median DoR was 15.4 months in patients with CR but differed significantly whether patients were transplanted or not (Not reached vs 8.4 months, p=.0055). Twenty-two patients (30% of patients ≤ 70 years of age) were transplanted (6 autologous and 16 allogenic). With a median follow-up of 9 months, the median PFS and OS were 8.3 and 26.3 months respectively. In multivariable analysis, only 2 factors had a significant impact on PFS and OS: best response (CR/PR vs SD/PD with a median PFS of 17.4 vs 1.9 months, p<.0001, and a median OS Not Reached vs 5,9 months, p<.0001) and transplantation (for patients in CR, median PFS was Not Reached in transplanted patients vs 13.1 months; p=.0410, and median OS was Not Reached vs 34, 6 months; p=.0304) (Fig1). Histological subgroups was also significantly associated with PFS (p=.012) but not with OS (p=.26) in multivariable analysis. Patients with PTCL NOS/Other subtypes had worse PFS than patients with TFH subtypes (HR=2.89 (95%CI: 1.4-5.8), p=.0029). Interestingly the CD30 status (positive vs negative) had no impact on ORR or survival. Fifty-nine percent of patients experienced a grade 3 to 4 adverse event which was mainly hematologic toxicity. Treatment had to be stopped in 11% of patients. Conclusion: To the best of our knowledge, this is the first study reporting on the combination of BBV in the treatment of R/R PTCL in such a large cohort. The results are very encouraging with a high response rate, long DoR in responding patients and a very good outcome. Furthermore, patients in CR who are eligible for transplant have the best outcome, making this combination a good candidate as salvage therapy before transplant consolidation in these high-risk lymphomas with limited treatment options. Figure 1 Figure 1. Disclosures Bouabdallah: Kite/Gilead: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Herbaux: Takeda: Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; Abbvie: Honoraria, Research Funding. Brice: MSD: Research Funding; Amgen: Other: Travel/accommodations/expenses; Roche: Other: Travel/accommodations/expenses; Takeda: Research Funding. Sibon: Abbvie: Consultancy; Janssen: Consultancy; Roche: Consultancy; iQone: Consultancy; Takeda: Consultancy. Laribi: AstraZeneca: Other: Personal Fees; AbbVie: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; Takeda: Other: Personal Fees, Research Funding; Novartis: Other: Personal Fees, Research Funding; Le Mans Hospital: Research Funding; Jansen: Research Funding. Damaj: roche: Consultancy, Honoraria; takeda: Consultancy, Honoraria. OffLabel Disclosure: Brentuximab Vedotin and Bendamustine

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