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ASH 2021: Safety and Efficacy of Third Generation CD20 Targeted CAR-T (MB-106) for Treatment of Relapsed/Refractory B-NHL and CLL

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Dr. Mazyar Shadman and colleagues presented this research at the American Society for Hematology annual meeting, which was held in December 2021 (ASH 2021).

Background:

CAR-T (Chimeric Antigen Receptor T-cell) therapy is a cellular immune treatment that involves taking cells from the patient and altering them to add a chimeric antigen receptor, such as CD19 (a marker found on the surface of all B cells). This allows them to attach to and destroy cancer cells that express CD19 on their surface. CD19-targeting CAR-T products are approved as standard treatment options for patients with relapsed diffuse large cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). However, targeting CD19 alone can lead to the downregulation of this protein by cancer cells, leading to relapse with disease that doesn’t express the target CD19 on the cell surface. In other words, it becomes CD19-negative and escapes detection by anti-CD19 CAR-T therapies. To address this challenge, researchers have been exploring CAR-T therapies that target different surface proteins, such as CD20.

Takeaways:

  • This is an ongoing phase I/II clinical trial investigating the safety and efficacy of CD20-targeted CAR-T (MB-106) for relapsed/refractory B-cell malignancies.
  • Thus far, 16 pts (12 FL, 2 MCL, 1 CLL, 1 DLBCL) have been treated.
  • Cytokine release syndrome occurred in 7 patients (44%).
  • Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 1 patient (6%).
  • Low platelet counts and low neutrophil counts were common, but there were no bleeding complications.
  • No patients had tumor lysis syndrome or severe/life-threatening infections
  • The overall response rate was 94% (15/16), with a complete response rate of 62% (10/16).
  • The one CLL patient had a complete response and undetectable measurable residual disease in peripheral blood and bone marrow on day 28.
  • Among patients who achieved a complete response, only one patient relapsed after 9 months, and all other complete responses are ongoing (range: 3-18 months).

Conclusions:

Thus far, treatment with MB-106 shows a favorable safety profile and high overall response and complete response rates. However, it is still early, so we will learn more as this research progresses. Results from phase 1 studies of bispecific CAR-T cells that target CD19 and CD20 have also been promising. At this time, CAR-T therapy is still considered experimental for CLL, and we will have to wait to see if CAR-T cells targeting CD20 prove more effective for treating CLL than CD19-targeted CAR-T cells.

Here is the link to the ASH 2021 abstract for more details.

Take care of yourself first.

Ann Liu, PhD

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