A Phase Ib/II Study of Anti-CD30 Chimeric Antigen Receptor T Cells for Relapsed/Refractory CD30+ Lymphomas

Grover, Natalie S; Park, Sophie; Ivanova, Anastasia; Eldridge, Paul W.; McKay, Kathryn; Cheng, Catherine; Laing, Spencer; Covington, Deborah L.; West, John A.; Sharf, Elizabeth; Morrison, J. Kaitlin; Scott, Shaw; Crecelius, Erin; Shelley, Desirae; Alexander, Mhairi E.; Buchanan, Faith Brianne; Kassam, Emily Herrick; McElfresh, Megan; Pinto, Alicia; Spruill, Angela; Zanter, Ashley; Wehner, Kimberly; Dittus, Christopher; Shea, Thomas C.; Dotti, Gianpietro; Serody, Jonathan S.; Beaven, Anne; Savoldo, Barbara

doi:10.1016/j.bbmt.2018.12.149

Cited by 11 publications

(9 citation statements)

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“…Data from two studies testing CAR-T therapy targeting the CD30 antigen in patients with HL were recently presented in the Transplantation and Cellular Therapy Meetings of American Society for Blood and Marrow Transplantation (ASBMT) and Center for International Blood & Marrow Transplant Research (CIBMTR) and highlight the potential role of anti-CD30 CAR-T cells for this disease [ 61 , 62 ]. In one of the trials, the investigators treated the patients with a lymphodepletion chemotherapy that included cyclophosphamide and fludarabine (FC) before CAR-T cell infusion.…”

Section: Car-t Therapy In Other Haematologic Malignancies: Is Thermentioning

confidence: 99%

“…In another Phase I/II study, patients received one of two dose levels in a standard 3 + 3 design. The doses tested in Phase I were 1 × 10 8 cells/m 2 or 2 × 10 8 cells/m 2 , and the Phase II part of the study tested the selected Phase I dose in more patients [ 62 ]. In both Phases of the study, a total of 29 patients were enrolled with a median age of 35 years (range: 23–69 years).…”

Section: Car-t Therapy In Other Haematologic Malignancies: Is Thermentioning

confidence: 99%

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CAR-T Therapy, the End of a Chapter or the Beginning of a New One?

Kamel

2021

Cancers

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Chimeric antigen receptor-T (CAR-T) therapy targeting CD19 has revolutionised the treatment of advanced acute lymphoblastic leukaemia (ALL) and diffuse large B-cell lymphoma (DLBCL). The ability to specifically target the cancer cells has shown high positive results as reported in the registration studies. The success of CAR-T therapy in the first two indications led to the initiation of a large number of studies testing CAR-T therapy in different haematologic tumours such as acute myelogenous leukaemia (AML), Hodgkin’s disease (HD), chronic lymphocytic leukaemia (CLL), multiple myeloma (MM), as well as different solid tumours. Unfortunately, relapses occurred in patients treated with CAR-T therapy, calling for the development of effective subsequent therapies. Likewise, this novel mechanism of action was also accompanied by a different toxicity profile, such as cytokine release syndrome (CRS). Patients’ access to the treatment is still limited by its cost. Notwithstanding, this did not prohibit further development of this new therapy to treat other malignancies. This research activity of CAR-T therapy moves it from being used as an end-stage treatment for ALL and DLBCL to a new therapeutic option for a wide range of patients with different haematologic and solid tumours.

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Section: Car-t Therapy In Other Haematologic Malignancies: Is Thermentioning

confidence: 99%

Section: Car-t Therapy In Other Haematologic Malignancies: Is Thermentioning

confidence: 99%

CAR-T Therapy, the End of a Chapter or the Beginning of a New One?

Kamel

2021

Cancers

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“…Bispecific antibodies The bispecific antibody AFM13 targets CD30 and CD16a to recruit natural killer cells to CD30-positive malignancies. A monotherapy study in 26 heavily-treated R/R HL patients demonstrated mild Phase Ib/II study [76] R/R HL Median 7.5 prior therapies (n = 22)…”

Section: Novel Consolidation Optionsmentioning

confidence: 99%

“…CAR-T cells CAR-T cell therapies targeting CD30, CD123, and Epstein-Barr virus (EBV)-related proteins are in development for the treatment of cHL, and are showing promising early results. Two US-based groups and one group in China have investigated CD30 CAR-T cell therapy in heavily-pretreated R/R HL with ORR rates of 67, 63, and 39%, respectively (Table 3) [75][76][77].…”

Section: Novel Consolidation Optionsmentioning

confidence: 99%

Improving outcomes after autologous transplantation in relapsed/refractory Hodgkin lymphoma: a European expert perspective

et al. 2020

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Autologous stem cell transplantation (ASCT) is a well-established approach to treatment of patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) recommended by both the European Society for Medical Oncology and the National Comprehensive Cancer Network based on the results from randomized controlled studies. However, a considerable number of patients who receive ASCT will progress/relapse and display suboptimal post-transplant outcomes. Over recent years, a number of different strategies have been assessed to improve post-ASCT outcomes and augment HL cure rates. These include use of pre- and post-ASCT salvage therapies and post-ASCT consolidative therapy, with the greatest benefits demonstrated by targeted therapies, such as brentuximab vedotin. However, adoption of these new approaches has been inconsistent across different centers and regions. In this article, we provide a European perspective on the available treatment options and likely future developments in the salvage and consolidation settings, with the aim to improve management of patients with HL who have a high risk of post-ASCT failure. Conclusions We conclude that early intervention with post-ASCT consolidation improves outcomes in patients with R/R HL who require ASCT. Future approvals of targeted agents are expected to further improve outcomes and provide additional treatment options in the coming age of personalized medicine.

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“…The majority of patients in these studies had HL. These trials are preliminary but show good tolerability and some modest effects [63][64][65] . Hill and colleagues presented the preliminary results of a phase I dose escalation study of a CD5-directed CAR-T cell therapy in RR T-cell leukemia and lymphoma patients as a bridge to allo-SCT 66 .…”

Section: Cellular Therapymentioning

confidence: 99%

Treatment approaches in relapsed or refractory peripheral T-cell lymphomas

Foster

Kuruvilla

2020

F1000Res

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Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare and aggressive non-Hodgkin’s lymphomas. Clinical staging, prognostic scoring, and initial treatment strategies have historically been based on paradigms developed in B-cell lymphomas. Despite primary treatment protocols that are typically anthracycline-based and frequently involve consolidative autologous stem cell transplantation in first remission, many patients develop disease progression. There remains a high unmet medical need for improved treatment strategies in the relapsed or refractory setting. Salvage chemotherapy and stem cell transplantation in those who are suitable has traditionally been the accepted approach, but this remains a minority of the total patient population. As increasing knowledge is gleaned regarding the biological heterogeneity within the various PTCL subtypes, newer targeted agents have been developed, studied, and approved in this small, heterogeneous population of relapsed or refractory disease. Given its success and tolerability in this pretreated population, brentuximab vedotin, an anti-CD30 antibody drug conjugate, was brought earlier in the disease course and is a model for advances in the targeted treatment of PTCL. As others undergo further development in the relapsed setting and successes are brought earlier in the disease course, the outcome for PTCL patients is likely to improve. However, innovative clinical trial designs are crucial for the assessment of targeted agents in this highly heterogeneous population. This review explores the current treatment environment for patients with relapsed and refractory PTCL, including newer strategies such as targeted agents and immunotherapy.

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A Phase Ib/II Study of Anti-CD30 Chimeric Antigen Receptor T Cells for Relapsed/Refractory CD30+ Lymphomas

Cited by 11 publications

References 0 publications

CAR-T Therapy, the End of a Chapter or the Beginning of a New One?

CAR-T Therapy, the End of a Chapter or the Beginning of a New One?

Improving outcomes after autologous transplantation in relapsed/refractory Hodgkin lymphoma: a European expert perspective

Treatment approaches in relapsed or refractory peripheral T-cell lymphomas

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