Brexucabtagene Autoleucel

A new clinical trial is investigating the use of Brexucabtagene Autoleucel, a promising CAR T-cell therapy, in combination with Pirtobrutinib for patients with relapsed or refractory mantle cell lymphoma. This study aims to evaluate the effectiveness and safety of this innovative treatment approach, potentially offering new hope for patients with this challenging form of blood cancer.

Table of Contents

What is Brexucabtagene Autoleucel?

Brexucabtagene Autoleucel, also known by its brand name Tecartus, is an innovative type of cancer treatment[1]. It belongs to a class of therapies called CAR T-cell therapy, which stands for Chimeric Antigen Receptor T-cell therapy. This treatment is specifically designed to target and fight certain types of cancer cells in your body.

Target Condition: Mantle Cell Lymphoma

Brexucabtagene Autoleucel is primarily used to treat a condition called Mantle Cell Lymphoma (MCL)[1]. MCL is a rare type of cancer that affects white blood cells called B lymphocytes, which are an important part of your immune system. This treatment is particularly valuable for patients with relapsed or refractory MCL, which means the cancer has either returned after initial treatment or did not respond well to other treatments.

How Brexucabtagene Autoleucel Works

Brexucabtagene Autoleucel is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy[1]. Let’s break down what this means:

  • Autologous: This means the therapy uses your own cells. Doctors collect some of your T-cells (a type of immune cell) from your blood.
  • CD19-directed: The collected T-cells are modified in a laboratory to target a specific protein called CD19, which is found on the surface of cancerous B-cells in MCL.
  • Chimeric Antigen Receptor (CAR): This is a special protein added to your T-cells that helps them recognize and attack cancer cells more effectively.

Once modified, these CAR T-cells are multiplied in the lab and then infused back into your body. They act like “super-soldiers” in your immune system, specifically targeting and destroying cancer cells that have the CD19 protein.

Current Clinical Trial

A new clinical trial is currently underway to further study the effectiveness of Brexucabtagene Autoleucel[1]. This trial is exploring how combining Brexucabtagene Autoleucel with another drug called Pirtobrutinib might improve outcomes for patients with relapsed or refractory Mantle Cell Lymphoma. Here are some key points about the trial:

  • It’s a Phase 2, open-label, randomized study.
  • The trial involves two groups (arms) of patients:
    • Arm A: Patients receive Pirtobrutinib before and during Brexucabtagene Autoleucel treatment.
    • Arm B: Patients receive Pirtobrutinib only before Brexucabtagene Autoleucel treatment.
  • The main goal is to see if adding Pirtobrutinib improves how long patients live without their cancer getting worse (progression-free survival).

Potential Benefits

The clinical trial aims to assess several potential benefits of Brexucabtagene Autoleucel treatment[1]:

  1. Improved Progression-Free Survival (PFS): This means patients may live longer without their cancer getting worse.
  2. Better Overall Response Rate (ORR): More patients may see their cancer shrink or disappear after treatment.
  3. Increased Overall Survival (OS): Patients may live longer overall compared to those receiving standard treatments.

Possible Side Effects

While Brexucabtagene Autoleucel can be very effective, it’s important to be aware of potential side effects. The clinical trial is monitoring two main side effects[1]:

  1. Immune Cell-Associated Neurotoxicity Syndrome (ICANS): This is a condition that can affect the nervous system. The trial is specifically looking at severe cases (grade 3 or higher) that occur within 60 days after the CAR T-cell infusion.
  2. Cytokine Release Syndrome (CRS): This is a condition where the immune system becomes overly active, causing symptoms like fever, nausea, and difficulty breathing. Again, the trial is focusing on severe cases (grade 3 or higher) within 60 days of treatment.

It’s crucial to discuss these potential side effects with your healthcare provider to understand the risks and benefits of this treatment.

Aspect Details
Study Type Phase 2, open-label, randomized, multicenter clinical trial
Condition Relapsed/refractory mantle cell lymphoma (R/R MCL)
Main Treatments Brexucabtagene Autoleucel (CAR T-cell therapy) and Pirtobrutinib
Study Arms Arm A: Concurrent Pirtobrutinib with Brexucabtagene Autoleucel
Arm B: Pirtobrutinib as bridging therapy only
Primary Outcomes Progression-free survival compared to historical control and between arms
Secondary Outcomes Severe ICANS and CRS rates, Overall Response Rate, Overall survival
Number of Participants 60 (30 in each arm)

Ongoing Clinical Trials on Brexucabtagene Autoleucel

  • Study on Extracellular Vesicles in Hematology Patients Treated with Brexucabtagene Autoleucel and Drug Combination

    Recruiting

    3 1 1 1
    France
  • Long-term Follow-up Study for Patients with Solid and Blood Cancers Treated with Brexucabtagene Autoleucel or Axicabtagene Ciloleucel

    Recruiting

    2 1 1 1
    Investigated diseases:
    Austria Belgium France Germany Italy The Netherlands +1
  • Study on CAR-T-cell Therapy with Rituximab and Ibrutinib for Patients with High-Risk Mantle Cell Lymphoma

    Recruiting

    2 1 1 1
    Czechia France Germany The Netherlands Spain
  • Study of fludarabine phosphate in patients with blood cancer undergoing lymphodepletion before CAR-T cell therapy

    Not yet recruiting

    3 1 1 1
    Investigated diseases:
    Belgium
  • Study on the Safety and Effectiveness of Brexucabtagene Autoleucel for Children and Teens with Relapsed or Refractory Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma

    Not recruiting

    1 1 1 1
    Investigated drugs:
    Czechia France Germany Italy Poland Spain
  • Study of Brexucabtagene Autoleucel in Patients with Relapsed or Refractory Mantle Cell Lymphoma

    Not recruiting

    2 1 1 1
    Investigated diseases:
    France Germany The Netherlands Spain
  • Study on Brexucabtagene Autoleucel for Adults with Relapsed/Refractory Hairy Cell Leukemia

    Not recruiting

    2 1 1 1
    Investigated diseases:
    Austria France Germany Italy The Netherlands Spain +1
  • Study on Brexucabtagene Autoleucel for Adults with Relapsed or Refractory Burkitt Lymphoma

    Not recruiting

    2 1 1 1
    Investigated diseases:
    Austria France Germany Italy The Netherlands Spain +1
  • Study on Brexucabtagene Autoleucel for Adults with Relapsed/Refractory Waldenstrom Macroglobulinemia Using a Drug Combination

    Not recruiting

    2 1 1 1
    Austria France Germany Italy The Netherlands Spain +1
  • Study on Brexucabtagene Autoleucel for Adults with Relapsed/Refractory Richter Transformation (RT)

    Not recruiting

    2 1 1 1
    Investigated diseases:
    Austria France Germany Italy The Netherlands Spain +1

Glossary

  • Mantle Cell Lymphoma (MCL): A type of blood cancer that affects a specific kind of white blood cell called B lymphocytes. It's a rare and aggressive form of non-Hodgkin lymphoma.
  • Relapsed/Refractory (R/R): Refers to cancer that has returned after treatment (relapsed) or has not responded to initial treatment (refractory).
  • CAR T-cell therapy: A type of treatment that uses a patient's own immune cells (T-cells) which are modified in a laboratory to better recognize and attack cancer cells.
  • Brexucabtagene Autoleucel (brexu-cel): A specific type of CAR T-cell therapy designed to target CD19, a protein found on certain cancer cells. It's also known by the brand name Tecartus.
  • Pirtobrutinib: A type of drug known as a non-covalent BTK inhibitor, which can be effective even when cancer cells have developed resistance to other similar drugs. It's also known by the brand name Jaypirca.
  • Bridging therapy: Treatment given to stabilize a patient's condition before they receive a main treatment, in this case, CAR T-cell therapy.
  • Progression-free survival (PFS): The length of time during and after treatment that a patient lives without their cancer getting worse.
  • ICANS: Immune effector Cell-Associated Neurotoxicity Syndrome, a potential side effect of CAR T-cell therapy affecting the nervous system.
  • CRS: Cytokine Release Syndrome, a potential side effect of CAR T-cell therapy that can cause fever, low blood pressure, and other symptoms.
  • Overall Response Rate (ORR): The percentage of patients whose cancer shrinks or disappears after treatment.
  • Lugano Criteria: A standardized set of guidelines used to assess how well lymphoma patients respond to treatment.
  • Overall survival (OS): The length of time from the start of treatment that patients are still alive.

References

  1. https://clinicaltrials.gov/study/NCT06553872