Rituxan

Rituximab was the first monoclonal antibody on the market. It goes by the brand name of Rituxan in the United States and Canada. In most of Europe it is known by the name Rituximab, and in Australia Mabthera.

Since its' debut in the USA in 1997 it has been the first new treatment to make a dramatic improvement in response rates, and survival rates for many forms of B-cell lymphomas. It is now approved in most countries around the world. Rituxan targets the CD20 antigen found on most B lymphocytes, both healthy and cancerous ones.

Rituxan was originally approved as a single agent treatment for relapsed indolent lymphoma. Response rates were modest. There was a 6% complete remission rate and a 42% partial remission rate for an overall response rate of 48%.

Further studies consistently showed that it had a synergistic effect when combined with most chemotherapy regimens. The first groundbreaking study by Bertrand Coiffier et al proved a significant improvement in response rates for elderly patients with Diffuse Large B-cell Lymphoma when treated with CHOP+Rituxan versus CHOP alone.

It is now standard practice to combine Rituxan with most chemotherapy regimens when treating B-cell lymphoma. Study after study has shown it dramatically improves the results.

Maintenance Rituxan

There is a great deal of study being done to see if maintenance Rituxan can further extend the survival and duration of remission for indolent lymphomas. The results are very positive. The initial studies had mixed results. They showed that patients receiving maintenance Rituxan stayed in remission longer than those who did not. But they also seemed to show that waiting until you relapsed and then using Rituxan again gave you the same results. In both cases the length of time until the patient no longer responded to single agent Rituxan and required stronger chemotherapy seemed to be the same. Therefore it was unclear if there would be any survival benefit.

Read the maintenance Rituxan versus re-treatment study by Hainsworth et al here

Although that study could not conclude there was any survival benefit, recent studies are beginning to show a 3 and 5 year survival benefit. We will have to wait for further follow up to see what is happening at the 10 and 15 year point since many follicular lymphoma patients would normally survive that long even without Rituxan.

Various maintenance Rituxan protocols are now being studied. Four infusions on a weekly basis every six months is the most common, but one infusion every 2 or 3 months is also under investigation. Nearly all of them use maintenance Rituxan for a maximum of two years. Nothing magical about two years, it is just that they do not wish to severely deplete the lymphocytes for too long and leave the patient open to infections. (Cost is also a factor)

Read the article below for a recent paper about the role of maintenance Rituxan for follicular lymphoma, by Dr. David Maloney from the Fred Hutchinson Cancer Center in Seattle Washington.
What is the role of maintenance Rituxan in follicular lymphoma?

Here is another discussion about whether or not maintenance Rituxan should be used. It is from two very prominent lymphoma specialists, one who is in favour of maintenance Rituxan, and one who is not.

Should maintenance Rituximab for follicular NHL be routine?

Here are a few of the abstracts about various maintenance Rituxan studies that are ongoing.  The first link is a summary of all of them. The first abstract below the summary uses a schedule of one infusion every three months, though it does not say that in the title. The final two links are highly focused searches of the US National Library of Medicine, and the prestigious Blood Journal for specific maintenance Rituxan articles.

A detailed summary of all the current maintenance Rituxan studies

This is a good article to read if you don't want to read all the studies below, but want to know the overall results of them all.

• Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial
  
  
• Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide and mitoxantrone (R-FCM) in patients with relapsed and refractory follicular and mantle cell lymphomas - results of a prospective randomized study of the German low grade lymphoma study group (GLSG)
  
  
• Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial
  
  
• Individualized Rituximab Dosing for Patients With CD20-Positive Lymphoproliferative Disorders
  
  
• Rituximab-CHOP Versus CHOP Alone or With Maintenance Rituximab in Older Patients With Diffuse Large B-Cell Lymphoma
  
  
• A good summary from the NHL update series, by Dr. Andrew Zelenetz, which discusses the use of Rituxan maintenance (is laymans terms)
  

Focused searches for articles about Maintenance Rituxan
Click here for a focused search about Maintenance Rituxan from PubMed

Click here for a focused search about Maintenance Rituxan from Blood

Rituxan Risks

While Rituxan is arguably the safest treatment used for NHL it is not entirely risk free. Perhaps the best source of  risk information is Rituxan's own boxed warnings.

Here are some articles about the possible risks of Rituxan treatment. Hypogammaglobulinemia is the most frequent. This big word just means low levels of the gamma globulin (antibodies) in the immune system.

• High incidence of non-neutropenic infections induced by Rituximab plus Fludarabine and associated with hypogammaglobulinemia: a frequently unrecognized and easily treatable complication
  
  
• B-cell recovery following Rituximab-based therapy is associated with perturbations in stromal derived factor-1 and granulocyte homeostasis
  
  
• Progressive multifocal leukoencephalopathy
  
  
• Adjuvant Rituximab causes prolonged hypogammaglobulinaemia following autologous stem cell transplant for non-Hodgkin's lymphoma.
  
  
• Delayed redistribution of CD27, CD40 and CD80 positive B cells and the impaired in vitro immunoglobulin production in patients with non-Hodgkin lymphoma after Rituximab treatment as an adjuvant to autologous stem cell transplantation.
  
  
• Hypogammaglobulinemia with a selective delayed recovery in memory B cells and an impaired isotype expression after rituximab administration as an adjuvant to autologous stem cell transplantation for non-Hodgkin lymphoma
  

Infectious events due to low lymphocyte counts are also quite common. These can occur months after treatment with Rituximab. One of the more commonly documented is Pneumonitis. There are many studies that document this as a rare complication, but no single study that summarizes them all. For more information go to our search page and type in "pneumonitis Rituximab"  without the quotes, then choose either Blood Journal or the NLM as your site to search, and you will find much more information.

Additional information

How Rituxan works. A detailed, but very technical look at its mechanism of action and causes of resistance

How it all started

Development of monoclonal antibodies began decades ago. But it was 1997 when Rituxan was first approved. It was at this point that some serious studies began, trying to figure out all the ways it could be used, and the best ways to use it. Below are some of those early studies, which many countries used as the basis for their own health agency approval process.

Effect of the addition of rituximab to front line therapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) on the remission rate and time to treatment failure (TTF) compared to CHOP alone in mantle cell lymphoma (MCL): Results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG).
 
Randomized intergroup trial of first line treatment for patients <=60 years with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) with a CHOP-like regimen with or without the anti-CD20 antibody rituximab - early stopping after the first interim analysis.
 
Randomized phase II study of concurrent and sequential combinations of rituximab (R) plus CHOP (R-CHOP) in untreated indolent B-cell non-Hodgkin's lymphoma (B-NHL).
 
Results of E1496: A phase III trial of CVP with or without maintenance rituximab in advanced indolent lymphoma (NHL).

Combined Immuno-Chemotherapy (R-CHOP) Significantly Improves Time To Treatment Failure in First Line Therapy of Follicular Lymphoma Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG).