CAN NEW DRUG COMBINATION PREVENT LYMPHOMA RELAPSE?

More potentially good news for lymphoma patients worldwide. An evidently powerful weapon in the growing arsenal of lymphoma-fighting drugs appears to be on its way toward human clinical trials in Europe.

Scientists in the UK are very optimistic that lymphoma patients could benefit from a chemical called R848, which triggers the body's immune system to fight cancer. Early lab results in mice have been promising, to say the least.

As reported in Science Daily, Medical News Today and other publications, R848, used in combination with radiation therapy, is four times more likely to result in long-term survival for lymphoma patients than radiation therapy alone, according to researchers at the University of Manchester.

Just what is R848? It's a chemical that sends signals to certain molecules known as receptors found on the surface of immune cells, triggering them into action. According to the new study published online in Blood, the Journal of the American Society of Hematology (ASH), researchers found that injections of R848 can generate a rapid expansion of specific anti-lymphoma immune cells known as "killer T cells."

A highly respected lymphoma patient advocate explains to me that R848 is a toll-like receptor agonist - just like CpG, which Pfizer shelved because there wasn't enough money in it. TRL agonists are immune stimulators. So the strategy is to use the radiation to kill most of the lymphoma to deliver a clinical complete response, the advocate says.

But that is not the same as a molecular complete response and some lymphoma cells remain. So this approach (which others are also using) is to follow induction therapy with an immunostimulator - such as R848, CpG or lenalidomide (Revlimid) - to prompt the immune system to continue policing and subduing malignant cells. The goal is to prolong PFS. Such is the hope in the ECOG trial using Revlimid as a maintenance therapy. 

In indolent lymphomas, the immune system plays a big role, hence waxing and waning, the advocate says. The immunomodulators, including the toll-like receptors, turbo charge immune therapies and can even act on their own - but are so much stronger when used with something like Rituxan, another antibody or a vaccine.  

One patient I know received vaccine + CpG and she and others like her responded well. There's a new trial for the BiovadID vaccine teaming it with lenalidomide, another immunostimulator. Studies of Rituxan paired with Revlimid (lenalidomide) have been showing excellent results. 

CpG is a TLR9 agonist and R848 is a TLR7 & 8 agonist. The patient advocate tells me that there is some preliminary evidence out of Ron Levy's lab that suggests TRL 7 & 8 may not as effective as TRL 9 (which CpG targets). However there is not a lot of data on this as of yet.

Dr. Simon Dovedi of the University of Manchester's Institute of Cancer Sciences and the Manchester Cancer Research Centre, said of R848 in a statement: 

"Excitingly, we think that this new approach to treating cancer could be capable of giving patients a better response to conventional therapies through the generation of a lymphoma-specific immune response against tumor cells. This could be the key to ensuring long-term survival in more patients and reducing the number of relapses after initial therapy."

The Manchester researchers tested injections of R848 in combination with radiation therapy in lab mice with lymphoma. It was found to have few side effects, with 100 percent of mice achieving long-term survival compared to just 28 percent of those mice that were treated with radiation therapy alone. 

In those mice that achieved long-term survival, any reintroduction of cancer was completely rejected by the immune system in 75 percent of cases. That's pretty impressive.

Early phase clinical trials of R848 for human patients with lymphoma are expected to happen soon. How long it takes for this med to make its way to North America, though, is still anyone's guess.

Professor Chris Bunce, Research Director of Leukaemia & Lymphoma Research in the UK, said in a statement: 

"While it is still early and this treatment has not yet been tested in humans, these results are hugely promising. One of the major obstacles to long-term successful treatment for many types of lymphoma has been relapse after initial successful treatment. Treatment with R848 can prime T cells to recognize various tumour-associated antigens, protecting patients from the return of the cancer."