clinical topic updates

Immunologic Treatment Strategies in Mantle Cell Lymphoma

by John M. Pagel, MD, PhD

Overview

Immune-based therapeutic approaches are actively being investigated and developed for mantle cell lymphoma (MCL). These include monoclonal antibodies, anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, and bispecific T-cell engagers.

Expert Commentary

John M. Pagel, MD, PhD

Chief of Hematologic Malignancies
Center for Blood Disorders and Stem Cell Transplantation

Swedish Cancer Institute

Seattle, WA


“Cellular and antibody-based therapies in MCL are rapidly emerging and have the potential to be game changing.”

John M. Pagel, MD, PhD

Cellular and antibody-based therapies in MCL are rapidly emerging and have the potential to be game changing. I think that among the most exciting are the CAR T-cell approaches. These therapies have been associated with excellent response rates. A phase 2 trial evaluating brexucabtagene autoleucel reported an objective response rate of well over 80%, with approximately 60% of patients achieving complete remission. These responses occurred very early and appeared to be relatively durable. The progression-free survival was reported at greater than 60%. Many of the patients in this study had failed prior treatments. Some patients may require a type of bridging therapy between the time of cell collection and the reinfusion of the engineered CAR T cells, and Bruton tyrosine kinase inhibitors might be a part of the process.

Another type of immunotherapy coming down the pike are the antibody-drug conjugates. Most recently, Wang and colleagues reported the results of their phase 1 study of VLS-101, an investigational antibody-drug conjugate that targets the novel antigen ROR1. Early data suggest that this antibody-drug conjugate is highly effective in patients with relapsed/refractory MCL, with approximately half of these patients achieving remissions that can be very durable.

There is also currently an emergence of bispecific antibodies. These novel agents target primarily CD20 on the mantle cell surface and CD3 on the cytotoxic T cell, and they stimulate the T cell to initiate cytotoxic activity against the associated found mantle cell. The early data with these agents are extremely promising, and we are excited about the possibility of seeing them emerge on the treatment landscape very soon.

We are expanding into new territory, building on the established foundation of immune-based approaches in MCL. For instance, we have had single-agent anti-CD20 antibodies such as rituximab and obinutuzumab for quite some time; and lenalidomide, which has also been used in oncology for some time, has immunomodulatory effects, which may be beneficial in patients with relapsed/refractory MCL. Finally, now we have brexucabtagene autoleucel, a CD19-directed CAR T-cell therapy approved for the treatment of relapsed or refractory MCL.

References

Hanel W, Epperla N. Emerging therapies in mantle cell lymphoma. J Hematol Oncol. 2020;13(1):79. doi:10.1186/s13045-020-00914-1

Jacobson CA, Maus MV. C(h)AR-ting a new course in incurable lymphomas: CAR T cells for mantle cell and follicular lymphomas. Blood Adv. 2020;4(22):5858-5862. doi:10.1182/bloodadvances.2020003391 

Wang M, Barrientos JC, Furman RR, et al. VLS-101, a ROR1-targeting antibody-drug conjugate, demonstrates a predictable safety profile and clinical efficacy in patients with heavily pretreated mantle cell lymphoma and diffuse large B-cell lymphoma [abstract 121]. Abstract presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020. 

Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382(14):1331-1342. doi:10.1056/NEJMoa1914347

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