This research was presented by Dr. Arnon Kater and colleagues at the American Society for Hematology annual meeting which was held December 2021 (ASH 2021).
Background:
Bispecific antibodies are a new experimental class of immunotherapy drugs which work by bringing your immune cells in close proximity to cancer cells. Antibodies are Y-shaped proteins. The bispecific antibody epcoritamab uses one arm of the Y to bind CD3, which is on the surface of T cells, and the other arm to bind CD20, which is on the surface of chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) cells. This brings the T cell and CLL / SLL cells close together so that the T cells can better recognize and destroy the CLL / SLL cells. T cells are part of the “cellular” immune system that are modified with CAR-T therapy. The hope is that bispecific antibodies can more simply and more safely provide similar benefits to those seen with CAR-Ts.
Takeaways:
- The Epcore CLL-1 trial is an open-label, multicenter, phase 1b/2 trial, evaluating the safety and efficacy of epcoritamab in adults with relapsed/refractory CLL.
- Thus far, 7 patients have enrolled in the study and received epcoritamab at either 24 mg or 48 mg.
- Epcoritamab was administered as subcutaneous injections in 4-week cycles.
- Researchers evaluated safety by looking at the incidence and severity of the following:
- Dose-limiting toxicities (DLTs): side effects of a treatment that are serious enough to prevent an increase in dose or level of that treatment
- Result: None occurred
- Adverse events (AEs): An unexpected medical problem that happens during treatment with a drug or other therapy. Adverse events may be mild, moderate, or severe, and may be caused by something other than the drug or therapy being given.
- Result: The most common AEs were cytokine release syndrome (100%), fatigue (71%), injection-site reaction (43%), and nausea (43%).
- Cytokine release syndrome (CRS): Immunotherapy can cause a large, rapid release of cytokines 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.
- Result: All patients experienced CRS in the first treatment cycle, but symptoms were generally mild
- Immune effector cell–associated neurotoxicity syndrome (ICANS): Neurologic adverse events that can cause confusion, tremors, or difficulty with communication.
- Result: No cases occurred
- Tumor lysis syndrome (TLS): When tumor cells die, they break apart and release their contents into the blood. When a lot of tumor cells die rapidly (such as when starting a new potent treatment), this can cause a change in certain chemicals in the blood, which may cause damage to organs, including the kidneys, heart, and liver.
- Result: No cases occurred
- Dose-limiting toxicities (DLTs): side effects of a treatment that are serious enough to prevent an increase in dose or level of that treatment
Conclusions:
These data suggest that epcoritamab is well tolerated in patients with relapsed/refractory CLL at dose levels up to 48 mg. Obviously, safety was the main concern here, so the number of patients enrolled is quite small. As the trial expands, we will be watching whether the safety profile holds in a larger number of patients, and we also hope to learn more about efficacy.
Here is the link to the ASH 2021 abstract for more details.
Take care of yourself first.
Ann Liu, PhD
