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ASH 2021: Safety and Anti-Tumor Activity of Plamotamab (XmAb13676), an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Subjects with Relapsed/Refractory Non-Hodgkin’s Lymphoma

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Dr. Krish Patel and colleagues presented this research at the American Society for Hematology annual meeting held December 2021 (ASH 2021).

Background:

Non-Hodgkin lymphoma (NHL) is a group of many different subtypes of cancer, which all start in your immune system’s white blood cells (lymphocytes). For example, chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are both types of NHL that start in the body’s B-cells and tend to grow slowly.

Bispecific antibodies are a new experimental class of immunotherapy drugs that work by bringing your immune cells in close proximity to cancer cells. The bispecific antibody plamotamab transiently links CD3-positive T cells to CD20-positive B-cells, inducing T-cell activation and subsequent destruction of cancer cells.

Takeaways:

  • This is a phase 1 clinical trial evaluating the safety and tolerability of plamotamab in patients with relapsed/refractory NHL.
  • There were three different dosing regimens to help researchers determine the maximum tolerated and recommended doses. This included a step-up dosing regimen where the dose increased over time and a flat dosing regimen where the dose level was kept the same over time.
  • Thus far, 80 patients have been treated with plamotamab.
  • Patients had a median of four prior therapies and had been diagnosed a median of 28 months prior to treatment in the study
  • The most common side effect was cytokine release syndrome (CRS), which was experienced by 63% of patients. Immunotherapy can cause a significant, rapid release of cytokines (proteins that stimulate inflammation) into the blood from affected immune cells. This can cause a number of symptoms, including fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing.
  • Cytokine release syndrome was generally manageable with premedication.
  • No severe or life-threatening neurotoxicity was observed.
  • Overall, efficacy could be evaluated in 53 patients, and of these patients, 43% had their disease decrease or disappear (objective response rate).
  • Four out of 16 (25%) evaluable subjects with prior CAR-T therapy responded to plamotamab.
  • The study is still ongoing to optimize the dose and dosing schedule.

Conclusions:

As this is an ongoing phase 1 clinical trial, these results should be considered preliminary and were more about safety than efficacy. Thus far, the side effects seen with plamotamab seem to be similar to those seen with other immunotherapies such as CAR-T therapy and other bispecific antibodies. In addition, some but not all patients showed evidence of anti-tumor activity as the amount of cancer decreased. Further studies would be needed to determine if this translates into better long-term outcomes. We look forward to learning more about the safety and efficacy of plamotamab as clinical trials progress.

Bispecific antibody research is more advanced in other lymphomas but holds promise in CLL/SLL, so we are encouraged to see trials with plamotamab and other bispecifics rolling out for those with CLL/SLL.

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

Take care of yourself first.

Ann Liu, PhD