How we treat mature B-cell neoplasms (indolent B-cell lymphomas)

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Abstract

Mature B cell neoplasms, previously indolent non-Hodgkin lymphomas (iNHLs), are a heterogeneous group of malignancies sharing similar disease courses and treatment paradigms. Most patients with iNHL have an excellent prognosis, and in many, treatment can be deferred for years. However, some patients will have an accelerated course and may experience transformation into aggressive lymphomas. In this review, we focus on management concepts shared across iNHLs, as well as histology-specific strategies. We address open questions in the field, including the influence of genomics and molecular pathway alterations on treatment decisions. In addition, we review the management of uncommon clinical entities including nodular lymphocyte-predominant Hodgkin lymphoma, hairy cell leukemia, splenic lymphoma and primary lymphoma of extranodal sites. Finally, we include a perspective on novel targeted therapies, antibodies, antibody–drug conjugates, bispecific T cell engagers and chimeric antigen receptor T cell therapy.

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Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

Armin Ghobadi, William Y Go, Jeff Wiezorek … (2017)

In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.

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ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells

Daniel W. Lee, Bianca D. Santomasso, Frederick L. Locke … (2019)

Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging as one of the most promising therapies for hematologic malignancies. Two CAR T products were recently approved in the United States and Europe for the treatment ofpatients up to age 25years with relapsed or refractory B cell acute lymphoblastic leukemia and/or adults with large B cell lymphoma. Many more CAR T products, as well as other immunotherapies, including various immune cell- and bi-specific antibody-based approaches that function by activation of immune effector cells, are in clinical development for both hematologic and solid tumor malignancies. These therapies are associated with unique toxicities of cytokine release syndrome (CRS) and neurologic toxicity. The assessment and grading of these toxicities vary considerably across clinical trials and across institutions, making it difficult to compare the safety of different products and hindering the ability to develop optimal strategies for management of these toxicities. Moreover, some aspects of these grading systems can be challenging to implement across centers. Therefore, in an effort to harmonize the definitions and grading systems for CRS and neurotoxicity, experts from all aspects of the field met on June 20 and 21, 2018, at a meeting supported by the American Society for Transplantation and Cellular Therapy (ASTCT; formerly American Society for Blood and Marrow Transplantation, ASBMT) in Arlington, VA. Here we report the consensus recommendations of that group and propose new definitions and grading for CRS and neurotoxicity that are objective, easy to apply, and ultimately more accurately categorize the severity of these toxicities. The goal is to provide a uniform consensus grading system for CRS and neurotoxicity associated with immune effector cell therapies, for use across clinical trials and in the postapproval clinical setting.

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Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas

Stephen Schuster, Jakub Svoboda, Elise Chong … (2017)

BACKGROUND Patients with diffuse large B-cell lymphoma or follicular lymphoma that is refractory to or that relapses after immunochemotherapy and transplantation have a poor prognosis. High response rates have been reported with the use of T cells modified by chimeric antigen receptor (CAR) that target CD19 in B-cell cancers, although data regarding B-cell lymphomas are limited. METHODS We used autologous T cells that express a CD19-directed CAR (CTL019) to treat patients with diffuse large B-cell lymphoma or follicular lymphoma that had relapsed or was refractory to previous treatments. Patients were monitored for response to treatment, toxic effects, the expansion and persistence of CTL019 cells in vivo, and immune recovery. RESULTS A total of 28 adult patients with lymphoma received CTL019 cells, and 18 of 28 had a response (64%; 95% confidence interval [CI], 44 to 81). Complete remission occurred in 6 of 14 patients with diffuse large B-cell lymphoma (43%; 95% CI, 18 to 71) and 10 of 14 patients with follicular lymphoma (71%; 95% CI, 42 to 92). CTL019 cells proliferated in vivo and were detectable in the blood and bone marrow of patients who had a response and patients who did not have a response. Sustained remissions were achieved, and at a median follow-up of 28.6 months, 86% of patients with diffuse large B-cell lymphoma who had a response (95% CI, 33 to 98) and 89% of patients with follicular lymphoma who had a response (95% CI, 43 to 98) had maintained the response. Severe cytokine-release syndrome occurred in 5 patients (18%). Serious encephalopathy occurred in 3 patients (11%); 2 cases were self-limiting and 1 case was fatal. All patients in complete remission by 6 months remained in remission at 7.7 to 37.9 months (median, 29.3 months) after induction, with a sustained reappearance of B cells in 8 of 16 patients and with improvement in levels of IgG in 4 of 10 patients and of IgM in 6 of 10 patients at 6 months or later and in levels of IgA in 3 of 10 patients at 18 months or later. CONCLUSIONS CTL019 cells can be effective in the treatment of relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. High rates of durable remission were observed, with recovery of B cells and immunoglobulins in some patients. Transient encephalopathy developed in approximately one in three patients and severe cytokine-release syndrome developed in one in five patients. (Funded by Novartis and others; ClinicalTrials.gov number, NCT02030834.)

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Erel Joffe:

ORCID: http://orcid.org/0000-0002-7883-289X

joffee@mskcc.org

Journal

Journal ID (nlm-ta): J Hematol Oncol

Journal ID (iso-abbrev): J Hematol Oncol

Title: Journal of Hematology & Oncology

Publisher: BioMed Central (London )

ISSN (Electronic): 1756-8722

Publication date (Electronic): 6 January 2021

Publication date PMC-release: 6 January 2021

Publication date Collection: 2021

Volume: 14

Electronic Location Identifier: 5

Affiliations

GRID grid.51462.34, ISNI 0000 0001 2171 9952, Lymphoma Service, Department of Medicine, , Memorial Sloan Kettering Cancer Center, ; 1275 York Avenue, SR‐441B, New York, NY 10065 USA

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Erel Joffe http://orcid.org/0000-0002-7883-289X

Article

Publisher ID: 1018

DOI: 10.1186/s13045-020-01018-6

PMC ID: 7789477

PubMed ID: 33407745

SO-VID: 8c3a5474-5453-48a1-b794-af306ad4b227

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Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 26 August 2020

Date accepted : 2 December 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000054, National Cancer Institute;

Award ID: 2P30CA008748-48

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: indolent lymphoma,mature b cell neoplasm,follicular lymphoma,marginal zone lymphoma,active surveillance

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: indolent lymphoma, mature b cell neoplasm, follicular lymphoma, marginal zone lymphoma, active surveillance

How we treat mature B-cell neoplasms (indolent B-cell lymphomas)

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Cancer Immunotherapy

Most cited references 239

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells

Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas

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