A Phase 1 Study of the Anti-CD37 Antibody-Drug Conjugate AGS67E in Advanced Lymphoid Malignancies. Interim Results

Sawas, Ahmed; Savage, Kerry J.; Perez, Raymond P.; Advani, Ranjana H.; Butturini, Anna; Lackey, Jacqueline; Trave, Fabio; Anand, Banmeet; Huang, Yao; Reyno, Leonard; O’Connor, Owen A.

doi:10.1182/blood.v126.23.3976.3976

Cited by 17 publications

(17 citation statements)

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“…Some patients, including a patient with multiply relapsed mycosis fungoides, continued receiving the drug with a deep partial response for more than 2 years. 39 Thus, given the expression profile in normal tissues and in B-and T-cell lymphomas, along with clinical safety data validating it as a target antigen, we chose to test and develop CAR T cells directed to CD37.…”

Section: Discussionmentioning

confidence: 99%

Anti-CD37 chimeric antigen receptor T cells are active against B- and T-cell lymphomas

Scarfò

Ormhøj

Frigault

et al. 2018

Blood

121

102

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Chimeric antigen receptor (CAR) T cells have emerged as a novel form of treatment of patients with B-cell malignancies. In particular, anti-CD19 CAR T-cell therapy has effected impressive clinical responses in B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma. However, not all patients respond, and relapse with antigen loss has been observed in all patient subsets. Here, we report on the design and optimization of a novel CAR directed to the surface antigen CD37, which is expressed in B-cell non-Hodgkin lymphomas, in chronic lymphocytic leukemia, and in some cases of cutaneous and peripheral T-cell lymphomas. We found that CAR-37 T cells demonstrated antigen-specific activation, cytokine production, and cytotoxic activity in models of B- and T-cell lymphomas in vitro and in vivo, including patient-derived xenografts. Taken together, these results are the first showing that T cells expressing anti-CD37 CAR have substantial activity against 2 different lymphoid lineages, without evidence of significant T-cell fratricide. Furthermore, anti-CD37 CARs were readily combined with anti-CD19 CARs to generate dual-specific CAR T cells capable of recognizing CD19 and CD37 alone or in combination. Our findings indicate that CD37-CAR T cells represent a novel therapeutic agent for the treatment of patients with CD37-expressing lymphoid malignancies.

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Section: Discussionmentioning

confidence: 99%

Anti-CD37 chimeric antigen receptor T cells are active against B- and T-cell lymphomas

Scarfò

Ormhøj

Frigault

et al. 2018

Blood

121

102

View full text Add to dashboard Cite

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“…Eleven (22%) patients experienced ORR, and seven (14%) patients achieved CR, four of whom had DLBCL. Peripheral neuropathy (16%) and neutropenia (8%) were the major AEs [118].…”

Section: Anti-cd37 Adcsmentioning

confidence: 99%

Antibody-drug conjugates in clinical trials for lymphoid malignancies and multiple myeloma

Liu

2019

J Hematol Oncol

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Antibody-drug conjugates (ADC) represent a distinct family of chemoimmunotherapy agents. ADCs are composed of monoclonal antibodies conjugated to cytotoxic payloads via specialized chemical linkers. ADCs therefore combine the immune therapy with targeted chemotherapy. Due to the distinct biomarkers associated with lymphocytes and plasma cells, ADCs have emerged as a promising treatment option for lymphoid malignancies and multiple myeloma. Several ADCs have been approved for clinical applications: brentuximab vedotin, inotuzumab ozogamicin, moxetumomab pasudotox, and polatuzumab vedotin. More novel ADCs are under clinical development. In this article, we summarized the general principles for ADC design, and updated novel ADCs under various stages of clinical trials for lymphoid malignancies and multiple myeloma.

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“…AGS67E is a human IgG2 antibody conjugated to MMAE. In a phase I trial of 50 patients with B and T cell NHL (only 2 patients with MCL), it demonstrated an ORR of 22% (CR rate = 11%) [74]. Expansion cohorts of DLBCL and cutaneous T cell lymphoma are ongoing.…”

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

Emerging therapies in mantle cell lymphoma

Hanel

Epperla

2020

J Hematol Oncol

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Mantle cell lymphoma (MCL) is a rare, B cell non-Hodgkin's lymphoma with highly heterogeneous clinical presentation and aggressiveness. First-line treatment consists of intensive chemotherapy with autologous stem cell transplant for the fit, transplant eligible patients, or less intensive chemotherapy for the less fit (and transplantineligible) patients. Patients eventually relapse with a progressive clinical course. Numerous therapeutic approaches have emerged over the last few years which have significantly changed the treatment landscape of MCL. These therapies consist of targeted approaches such as BTK and BCL2 inhibitors that provide durable therapeutic responses. However, the optimum combination and sequencing of these therapies is unclear and is currently investigated in several ongoing studies. Furthermore, cellular therapies such as chimeric antigen receptor (CAR) T cells and bispecific T cell engager (BiTe) antibodies have shown impressive results and will likely shape treatment approaches in relapsed MCL, especially after failure with BTK inhibitors. Herein, we provide a comprehensive review of past and ongoing studies that will likely significantly impact our approach to MCL treatment in both the frontline (for transplant eligible and ineligible patients) as well as in the relapsed setting. We present the most up to date results from these studies as well as perspectives on future studies in MCL.

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A Phase 1 Study of the Anti-CD37 Antibody-Drug Conjugate AGS67E in Advanced Lymphoid Malignancies. Interim Results

Cited by 17 publications

References 0 publications

Anti-CD37 chimeric antigen receptor T cells are active against B- and T-cell lymphomas

Anti-CD37 chimeric antigen receptor T cells are active against B- and T-cell lymphomas

Antibody-drug conjugates in clinical trials for lymphoid malignancies and multiple myeloma

Emerging therapies in mantle cell lymphoma

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