Identifying POD24 in Follicular Lymphoma?

The Journal of Clinical Oncology just published "Progression of Disease Within 24 Months in Follicular Lymphoma Is Associated With Reduced Intratumoral Immune Infiltration." It has potentially important implication for some Follicular Lymphoma patients.

Some background first:

About 20% of Follicular Lymphoma patients are grouped as "POD24" (also known as EFS24, and by a couple of other names). "POD" stands for "Progression of Disease," and POD24 is short for patients who have had their disease progress within 24 months after receiving Immunochemotherapy (like R-CHOP or R-Bendmustine). EFS24, Event-Free Survival, is a very similar concept to POD, so the group of patients goes by that name, too.

(Patients who have had other treatments, like straight Rituxan, and who progress within 24 months, aren't part of this group. Anything related to POD24 or EFS24 doesn't apply to them.)

POD24 patients, unfortunately, have a lower overall survival than other FL patients who response to Immunochemotherapy lasts longer than 24 months. Unfortunately, there still isn't a way to predict whether a patient falls into this group. The only way to tell is to give Immunochemo and then wait 24 months. If doctors could tell who falls into that group, they may be able to give more aggressive therapy early on, or researchers can begin working on a treatment specifically for that group.

The JoC research may be a step in that direction. Researchers know that patients with solid tumors (a cancer other than a blood cancer) who have lower levels of Tumor Immune Infiltration tend to have earlier progression. Tumor Immune Infiltration refers to the levels of immune cells that are present inside a tumor. The body produces a lot of immune cells -- B cells, T cells, etc, -- that help fight ff invaders like viruses and bacteria. They usually don't fight off cancer cells because cancer isn't an invader -- it's our own cells, acting badly. However, researchers who looked at solid tumors found that when certain immune cells have penetrated the tumor, a high level of them usually meant a better outcome for the patient.

Using this knowledge, they looked for levels of immune cells to figure out if those levels were related to POD24. They looked at the presence of 12 immune molecules in the patients, and found that 6 were possibly related to POD24. To test the idea, they looked at 138 patients who had received the Immunochemo R-CVP, and 45 who had received R-CHOP.

In the end, they found one molecule that was very promising as a POD24 predictor -- PD-L2, Programmed Death Ligand 2. A "ligand" is a kind of cell that attaches to another cell. In this case, PD-L2 is on the surface of the cancer cell, and attaches to an immune cell, signalling to the immune cell that it should not attack the cancer cell. The body's immune response is lowered, and the cancer cells are safe.

So, to sum that all up: finding lots of immune cells in a tumor is a sign that a treatment is probably going to do a good job. In FL patients, if PD-L2 is found, there will be fewer immune cells, because the PD-L2 told them to stay away. So the response to treatment won't be as good.

The significance of this? If doctors find PD-L2, they can be ore aggressive in their treatment in hopes that the patient won't progress beyond 24 months. And researchers can find ways to inhibit PD-L2.

There have been lots of folks in the Lymphoma community in the last few years who have said that helping POD24/EFS24 patients is a priority. Identifying them was a great first step, and now finding biomarkers that let doctors know who is at risk as a great second step. Let's hope this researcher plays a part in that.