CD20 Expression and Anti-Tumor Activity of Columvi

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This article responds to your request for information on Columvi™ (glofitamab) and the need for CD20 expressing B-cells for anti-tumor activity.

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Last updated March 11, 2024

Summary

  • Columvi is an anti-CD20×CD3 T-cell engaging bispecific antibody that targets CD20 expressing B-cells.
    • Lysis of B-cells by Columvi does not occur in the absence of CD20 expression.
    • In the Columvi pivotal study, patients were not screened for CD20 expression.
      • Patients were eligible if they had a diagnosis of a B-cell malignancy associated with CD20 expression.
      • There is limited data in patients with CD20‑negative DLBCL treated with Columvi.
        • There is no recommendation for measuring levels of CD20 expressions prior to administration of Columvi.
          • The potential risks and benefits of treating patients with CD20-negative DLBCL with Columvi should be considered.

          Abbreviations

          DLBCL = diffuse large B-cell lymphoma

          Mechanism of action of Columvi and role of CD20 expression

          Columvi is a bispecific monoclonal antibody that binds to[1]

          • CD20 expressed on the surface of B cells, and
            • CD3 in the T-cell receptor complex expressed on the surface of T cells.

              By simultaneous binding to CD20 on the B cell and CD3 on the T cell, Columvi induces[1]

              • lysis of CD20-expressing B cells,
                • activation and proliferation of T‑cells, and
                  • release of cytokines.

                    Lysis of B cells mediated by Columvi is CD20‑specific and does not occur in the absence of[1]

                    • CD20 expression, or
                      • simultaneous binding of T cells to CD20‑expressing cells

                        Anti-tumor activity of Columvi in DLBCL with low CD20 expression

                        Data from non-clinical studies show[2,3]

                        • Columvi efficiently killed cell lines expressing very low levels of CD20.
                          • Evidence of Columvi’s in vitro activity includes lysis of 50% of tumor cells with 0.5% of CD20 receptor occupancy.
                          • tumor cell killing can efficiently occur in the presence of saturating levels of obinutuzumab, thus supporting the hypothesis that Columvi works effectively under conditions of limited CD20 access.

                            Anti-tumor activity of Columvi in CD20-negative DLBCL

                            Experience from clinical trials

                            There is limited data in patients with CD20‑negative DLBCL treated with Columvi.[4] CD20‑negative DLBCL is defined as less than 5% of CD20-positive cells in the tumor area.[4]

                            In the Columvi pivotal study, patients were not prescreened for CD20 expression because[5]

                            • data from non-clinical studies demonstrated anti-tumor activity of Columvi even with low CD20 expression,[2,3] and
                              • CD20 is expressed inthe majority of B-cell-derived human malignancies.
                                • Published reports show that CD20-negative B-cell-derived malignancies are rare.[6]

                                In the pivotal clinical trial, patients were eligible if they had a diagnosis of a B-cell malignancy associated with CD20 expression. Fresh tumor biopsy or archival tumor tissue samples was mandatory for entry into the study to: 

                                • assess CD20 expression, retrospectively,
                                  • determine prognostic or predictive factors, and
                                    • investigate baseline immune status.[2]
                                                             

                                      Three patients hadCD20-negative disease; all had progressive disease as their best response to Columvi and died during follow-up.[4] The efficacy of Columvi has not been established in patients with CD20-negative disease who have relapsed from prior anti-CD20 therapy.[4]

                                      In the Columvi pivotal study, patients who had progressed after completing treatment with 12 cycles of Columvi were strongly recommended to provide a fresh tumor sample for exploratory assessment of CD20 expression, before receiving retreatment with Columvi.[7]

                                      Case reports and published literature on the use of Columvi in patients with CD20‑negative DLBCL

                                      There are no case reports on the use of Columvi in patients with CD20‑negative DLBCL.

                                      Prescribing considerations for measurement of CD20 expression levels before administering Columvi

                                      There is no recommendation for assessment of CD20 expression prior to Columvi initiation.[1] However, the potential risks and benefits associated with treatment of patients with CD20-negative DLBCL with Columvi should be considered.[4] It is possible that patients with CD20-negative DLBCL may have less benefit compared to patients with CD20-positive DLBCL.[4] The decision to biopsy to assess the presence of CD20 prior to treatment with Columvi is left to the discretion of the healthcare provider. 

                                      References

                                      1. Roche Internal Regulatory Document (Columvi Core Data Sheet) (Accessed on 25 February 2024).
                                        1. Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med 2022;387:2220-2231. https://www.ncbi.nlm.nih.gov/pubmed/36507690
                                          1. Bacac M, Colombetti S, Herter S, et al. CD20-TCB with Obinutuzumab Pretreatment as Next-Generation Treatment of Hematologic Malignancies. Clin Cancer Res 2018;24:4785-4797. https://www.ncbi.nlm.nih.gov/pubmed/29716920
                                            1. European Medicines Agency (EMA). Committee for Medicinal Products for Human Use (CHMP) Assessment Report (EMA/228393/2023). 2023;98-99. https://www.ema.europa.eu/en/documents/assessment-report/columvi-epar-public-assessment-report_en.pdf
                                              1. Roche Internal Safety Report (Accessed on 04 March 2024).
                                                1. Maeshima AM, Taniguchi H, Nomoto J, et al. Prognostic implications of histologic grade and intensity of Bcl-2 expression in follicular lymphomas undergoing rituximab-containing therapy. Hum Pathol 2013;44:2529-35. https://www.ncbi.nlm.nih.gov/pubmed/23916290
                                                  1. Roche Internal Clinical Study Report (Protocol of Study NP30179) (Accessed on 02 March 2024).

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