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Radioimmunotherapy

 

Radioimmunotherapy

That is a very large word (usually shortened to RIT), but it has just as large a potential to influence the way we treat non Hodgkin's lymphoma. On this page we will try to explain what it is, how it works, and why it is so important that we all be aware of it. We'll also briefly address some of the reasons it is so underused.

What is radioimmunotherapy

Radioimmunotherapy is a treatment where they use a monoclonal antibody (very much like Rituxan) but they also attach a radioactive particle to it. This has the benefit of killing the lymphoma cell that the antibody is attached to, and ALSO killing many more cells that are in the radiation path. This means that even cells that do not have the antibody attached to them, will still be killed.  Since the antibody only attaches to lymphocytes that express the target antigen, nearly all normal tissue is spared any radiation.

Typically radioimmunotherapy uses an antibody that is fully mouse, and not part mouse and part human like Rituxan. They do this because your body will eliminate a mouse antibody faster than one that is partly human because it clearly recognizes the mouse antibody as foreign. This is important because they don't want the radiation particle staying in the body for too long.

At the present time there are two approved radioimmunotherapies for lymphoma, though others are in development.

  1. I-131 Tositumomab (brand name Bexxar) discontinued by GSK in February 2014.
  2. Y-90 Ibritumomab Tiuxetan (brand name Zevalin)

Read more about those specific therapies by clicking on their name on the menu to the left. 

Why is it so important

Since radioimmunotherapy combines both a cancer killing antibody directed specifically at lymphocytes, and the potent lymphoma killing ability of radiation, it has the potential to be more effective than chemotherapy or a plain antibody like Rituxan. Studies have shown that even when all other treatments have failed, radioimmunotherapy is still highly effective for many patients. In fact there are many people who have been heavily pre-treated with other treatments, then are given radioimmunotherapy which puts them into remission for years. Some patients are still in remission after 10-15 years. That is a pretty powerful argument in favour of using RIT more often.  Even patients who are refractory to their previous treatments, often get favourable responses with RIT.  This includes patients who are refractory to Rituximab.

Another unique benefit is the low toxicity. Since it targets only lymphocytes there are nearly no side effects other than myelosuppession. People go in for just a couple of injections and that is it. They are done. (see administration procedures for each drug on it's own page) This makes RIT very convenient for the patient.

Cost might prove to be another benefit. Although the initial cost for RIT is very high, the total cost to the health care system might turn out to be much lower if the patient stays in remission for many years and requires no further treatment and hospital resources. This is yet to be proven but it could be a persuasive argument if proven true.

Articles that discuss the benefits, limitations, and study results about RIT

Below are some articles from experts in the field, that discuss RIT in general. These articles are not medical studies, but rather editorials written by experts.

This first article discusses the results of many of the studies being done, and where RIT may fit into the current treatment practices, as well as the barriers to more widespread use.  The first one discusses several studies that were published in the same issue of the Journal of Clinical Oncology. See the references at the bottom of that article for the references and links to them.

  1. Moving Radioimmunotherapy Forward for Follicular Lymphoma

  2. Radioimmunotherapy in Non-Hodgkin Lymphoma: Opinions of Nuclear Medicine Physicians and Radiation Oncologists

  3. Radioimmunotherapy of Lymphoma: A Treatment Approach Ahead of Its Time or Past Its Sell-By Date?

  4. Moving Radioimmunotherapy Forward for Follicular Lymphoma

Next is an article that looks at pretargeting. First they inject a cold antibody, then another drug that flushes any free floating antibody out of the blood. Next a radioactive effector that seeks out and attaches to the original antibody which is attached to tumour cells. It then delivers its radiation directly to the tumour.

Some like it hot: lymphoma radioimmunotherapy

Here is a look at the purpose of the pre-dosing with naked antibody, and strategies to optimize pre-dosing by using non-competing antibodies.

A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: prospects for dual-targeted antibody/radioantibody therapy

Next a look at the mounting evidence that Radioimmunotherapy represents an important therapy that is not being used to its full potential.

Evidence Mounts for the Efficacy of Radioimmunotherapy for B-Cell Lymphomas

Here is a review of oncologists opinions about radioimmunotherapy.

Radioimmunotherapy in Non-Hodgkin Lymphoma: Opinions of U.S. Medical Oncologists and Hematologists

Why is radioimmunotherapy underused?

That is a more difficult question to answer. There are a number of factors that may be contributing to underuse of RIT

  1. RIT can only be mixed and administered by pharmacists, oncologists and haematologists who are licensed to mix/administer radiopharmaceuticals. Those are a tiny minority of all the practicing pharmacists/oncologists/haematologists
  2. Most haematologists/oncologists must refer their patients to another practice to get RIT if they are not licensed. This is a financial disincentive in some jurisdictions where haematologists/oncologists derive their livelihood from services they provide to their patients.
  3. Initial high cost
  4. Some doctors are not familiar with the body of evidence showing the benefits of RIT
  5. Doctor preference to stick with what they have found to be tried and true for their patients.

There may be other reasons as well. As patients, it is up to us to ensure we are educated about RIT and when it is appropriate to use. Then you should discuss RIT with your doctors if and when you feel it might be an important option for you.


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