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Autologous T-Cells Encoding A Chimeric Antigen Receptor Targeting Human B Cell Maturation Antigen

This article discusses clinical trials using autologous T-cells encoding a chimeric antigen receptor (CAR) targeting human B cell maturation antigen (BCMA) for the treatment of multiple myeloma. These innovative trials focus on a promising new therapy called CAR T-cell therapy, which involves modifying a patient’s own immune cells to fight cancer. The trials aim to evaluate the effectiveness and safety of this treatment in patients with relapsed and refractory multiple myeloma, as well as to monitor long-term outcomes in patients who have received CAR T-cell therapy.

Table of Contents

What is this treatment?

The treatment we’re discussing is called “AUTOLOGOUS T-CELLS ENCODING A CHIMERIC ANTIGEN RECEPTOR TARGETING HUMAN B CELL MATURATION ANTIGEN.” It’s a type of CAR-T cell therapy, which is a form of immunotherapy that uses a patient’s own modified immune cells to fight cancer. This specific treatment is also known by the product name PHE885 or durcabtagene autoleucel[1].

How does it work?

This therapy works by modifying a patient’s own T-cells (a type of immune cell) to target and attack cancer cells. Here’s a simplified explanation of the process:

  1. T-cells are collected from the patient’s blood through a process called leukapheresis.
  2. These T-cells are then genetically modified in a laboratory to produce special receptors on their surface called chimeric antigen receptors (CARs).
  3. The CARs are designed to recognize and attach to a specific protein called B-cell maturation antigen (BCMA), which is found on the surface of certain cancer cells.
  4. The modified T-cells are then multiplied in the laboratory and infused back into the patient.
  5. Once in the patient’s body, these CAR-T cells can recognize and attack cancer cells that have the BCMA protein on their surface[1].

What medical conditions does it treat?

This CAR-T cell therapy is being studied for the treatment of relapsed and refractory multiple myeloma in adults. Multiple myeloma is a type of blood cancer that affects plasma cells, a type of white blood cell that normally produces antibodies to help fight infections[1].

“Relapsed” means the cancer has returned after a period of improvement, while “refractory” means the cancer has not responded to previous treatments or has stopped responding[1].

Current Clinical Trials

There are currently two notable clinical trials involving this treatment:

  1. A Phase 2 study of durcabtagene autoleucel in adult patients with relapsed and refractory multiple myeloma[1].
  2. A long-term follow-up study for patients treated with CAR-T cell therapy, including PHE885[2].

Who is eligible for this treatment?

Based on the Phase 2 study, eligibility criteria include:

  • Adults aged 18 years or older
  • Diagnosed with relapsed and refractory multiple myeloma
  • Have received at least 3 prior lines of therapy, including specific types of drugs
  • Have measurable disease
  • Have an ECOG performance status of 0 or 1 (meaning they are relatively healthy and able to carry out daily activities)[1]

Some patients may not be eligible if they have had certain previous treatments or have specific medical conditions. It’s important to discuss eligibility with a healthcare provider[1].

How effective is the treatment?

The effectiveness of this treatment is being evaluated in the ongoing clinical trials. The main goal is to assess the overall response rate (ORR), which measures how many patients see their cancer shrink or disappear after treatment. Other important measures include:

  • How quickly patients respond to the treatment
  • How long the response lasts
  • How long patients live without their disease getting worse (progression-free survival)
  • How long patients survive overall
  • Whether the treatment eliminates all detectable cancer cells (minimal residual disease negativity)[1]

Safety and Side Effects

As with any medical treatment, there are potential side effects and risks. The clinical trials are closely monitoring for adverse events, including:

  • Cytokine release syndrome (a condition that can cause fever, chills, and other flu-like symptoms)
  • Neurological effects
  • Infections
  • Low blood cell counts
  • Other potential long-term effects[1][2]

Long-term Follow-up Study

To better understand the long-term effects of this and similar CAR-T cell therapies, a separate long-term follow-up study is being conducted. This study aims to:

  • Monitor for delayed side effects
  • Track how long the modified T-cells persist in the body
  • Assess long-term effectiveness
  • Monitor patients’ overall health, including growth and development in younger patients[2]

This long-term study will provide valuable information about the safety and durability of the treatment’s effects over time.

Aspect Details
Treatment Autologous T-cells encoding a chimeric antigen receptor targeting human B cell maturation antigen (BCMA CAR T-cells)
Target Condition Relapsed and refractory multiple myeloma in adults
Main Objectives Evaluate efficacy, safety, and long-term outcomes of CAR T-cell therapy
Key Eligibility Criteria Adults with relapsed/refractory multiple myeloma, ≥3 prior lines of therapy, measurable disease
Primary Endpoints Best overall response rate, proportion of patients with specific delayed adverse events
Secondary Endpoints Minimal residual disease negativity, duration of response, progression-free survival, overall survival
Administration Single intravenous infusion of modified T-cells
Follow-up Long-term monitoring for efficacy, safety, and persistence of modified T-cells

FAQ

  • What is CAR T-cell therapy? CAR T-cell therapy is a type of immunotherapy where a patient's own T-cells (a type of immune cell) are genetically modified to express a chimeric antigen receptor (CAR) that targets specific cancer cells. In this case, the CAR targets the B cell maturation antigen (BCMA), which is found on multiple myeloma cells.
  • Who is eligible for these clinical trials? The trials are primarily for adult patients with relapsed and refractory multiple myeloma who have received at least 3 prior lines of therapy, including specific types of drugs. Patients must meet certain criteria, such as having measurable disease and an acceptable performance status.
  • What are the main objectives of these clinical trials? The main objectives include evaluating the efficacy of the CAR T-cell therapy in terms of disease response, assessing safety, measuring the durability of response, and monitoring long-term outcomes such as overall survival and the occurrence of delayed side effects.
  • How is the CAR T-cell therapy administered? The therapy is administered as a single intravenous infusion. Before the infusion, patients undergo a process called leukapheresis to collect their T-cells, which are then genetically modified and multiplied in a laboratory before being infused back into the patient.
  • What kind of follow-up is involved after receiving the CAR T-cell therapy? Patients are monitored closely for immediate side effects and treatment response. Additionally, there is a long-term follow-up study to monitor for delayed side effects, persistence of the modified T-cells in the body, and long-term efficacy of the treatment. This follow-up can last for several years after the initial treatment.

Ongoing Clinical Trials on Autologous T-Cells Encoding A Chimeric Antigen Receptor Targeting Human B Cell Maturation Antigen

  • Long-Term Follow-Up Study for Patients Treated with CAR T-Cell Therapy Using PHE885, YTB323, and Tisagenlecleucel

    Recruiting

    3 1 1 1
    Investigated diseases:
    Investigated drugs:
    Austria Belgium Denmark Finland France Germany +6

  • Study of Durbactagene Autoleucel and Drug Combination for Adults with Relapsed and Refractory Multiple Myeloma

    Not recruiting

    2 1 1 1
    Investigated diseases:
    Investigated drugs:
    France Germany Greece Italy Spain

Glossary

  • Autologous: Derived from the patient's own cells or tissues. In this context, it refers to T-cells taken from the patient's own body.
  • Chimeric Antigen Receptor (CAR): A genetically engineered receptor added to T-cells that allows them to recognize and attack specific cancer cells.
  • B Cell Maturation Antigen (BCMA): A protein found on the surface of multiple myeloma cells, which is targeted by the CAR T-cells in this therapy.
  • Multiple Myeloma: A type of blood cancer that affects plasma cells, a type of white blood cell found in bone marrow.
  • Relapsed and Refractory: Refers to cancer that has returned after treatment (relapsed) and is not responding to current treatments (refractory).
  • Leukapheresis: A procedure to separate and collect white blood cells (including T-cells) from a patient's blood.
  • Overall Response Rate (ORR): The proportion of patients whose cancer shrinks or disappears after treatment.
  • Progression-Free Survival (PFS): The length of time during and after treatment that a patient lives without the cancer getting worse.
  • Overall Survival (OS): The length of time from the start of treatment that patients are still alive.
  • Minimal Residual Disease (MRD): A small number of cancer cells that remain in the body during or after treatment.

References

  1. http://clinicaltrials.eu/trial/study-of-durbactagene-autoleucel-and-drug-combination-for-adults-with-relapsed-and-refractory-multiple-myeloma/
  2. http://clinicaltrials.eu/trial/long-term-follow-up-study-for-patients-treated-with-car-t-cell-therapy-using-phe885-ytb323-and-tisagenlecleucel/