Thursday, August 3, 2017

Keytruda and Rituxan for Follicular Lymphoma

We're back to looking at some recent research in Follicular Lymphoma treatments.

At the 2017 International Conference on Malignant Lymphoma biennial meeting in Lugano, Switzerland in June, researchers presented early results from a phase II clinical trial for Rituxan and Pembrolizumab, also known as Keytruda (and since that's easier to spell, it's what I'm going to use).

Keytruda is an interesting treatment -- it has been tried out on a bunch of different cancers, not just FL, or even blood cancers. It is perhaps most famously been used in treating former U.S. President Jimmy Carter's brain cancer. It is the first treatment approved by the FDA for a biomarker, rather than a body part. In other words, most cancer treatments are approved for a cancer in the blood, or the lungs, or the colon. But Keytruda targets a genetic abnormality that is present in lots of different types of cancer. There are some oncology experts who say that is the future of cancer treatment, focusing on genes and not body parts.

Keytruda is a humanized monoclonal antibody (which explain the "-mab" at the end of its harder-to-spell name), like Rituxan (also known as rituximab). Just like Rituxan targets a protein on the surface of an immune cell, Keytruda targets the PD-1 receptor on an immune cell. PD-1 stands for Programmed Cell Death -1. The PD-1 receptor is important because it tells the body not attack itself -- it is known as an "immune checkpoint."

So here's where the problem comes: the cells for many different types of cancer will attach to the PD-1 receptor and block it. That means that the immune system can't recognize the cancer cell as an invader. While it would normally kill off the cancer cell, now it doesn't even know it's there, and the cancer cells grows and grows.

Keytruda is a "checkpoint inhibitor." It attaches itself to the PD-1 receptor, so the cancer cells can't. This lets the immune cell see the cancer cells as invaders, and destroy them. It's a great example of Immunotherapy, where the treatment helps the immune system do it's job normally to kill of invaders like cancer cells.

The phase II clinical trial that combined Keytruda with Rituxan involved a small number of patients (only 30), but the results were very good, with an 80% Overall Response Rate. Keytruda seems to help out certain types of immune cells that kill invaders in a particular way (that particular way is called Antibody-Dependent Cellular Cytotoxicity, or ADCC, in case you want to look it up). Conveniently, Rituxan works through ADCC. So the thinking of the researchers was that combining Keytruda and Rituxan would work well for Follicular Lymphoma.

The patients in the study have all had treatments with Rituxan in the past. As I said, the Overall Response Rate was 80%, with 60% achieving a Complete Response, after a follow-up of 7 months. Pretty good numbers. There were some side effects, particularly related to immune system problems (which is expected when you give a treatment that blocks the things that keep immune cells from controlling themselves). But they were considered manageable.

There are lots of limitations to this study -- it's a small number of people (just 30), and it was done at just one institution (MD Anderson), and the follow-up time is pretty short (7 months). But the researchers argue that these numbers are good enough to expand, and that would seem to be the case.

Keytruda is an interesting treatment, and it has seen a lot of success in lots of different cancers that are affected by the PD-1 receptor. But it's not perfect, by any means. In fact, about a month ago, trials for a combination therapy that included Keytruda for patients with Multiple Myeloma (another blood cancer) had to be stopped because of several deaths. Again, this treatment can do a number on the immune system, and certain combinations will probably make that affect worse. It's important to note that the Keytruda/Rituxan trial reported no deaths, but it's a good reminder that every treatment carries some risk.

For now, though, this may represent yet another non-chemotherapy treatment that is worth keeping an eye on.

[I didn't include a direct link to the abstract for this presentation at the International Conference on Malignant Lymphoma, because the ICML doesn't have a search function for their abstracts, so I can't give a direct link to just this one. However, if you want to see the abstract for yourself, then follow this link to the Abstract Book, then scroll down to abstract #109, "HIGH RESPONSE RATES WITH PEMBROLIZUMAB IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH RELAPSED FOLLICULAR LYMPHOMA: INTERIM RESULTS OF AN ON OPEN‐LABEL, PHASE II STUDY.]


Anonymous said...

Great article Bob. Lots of good treatments emerging for relapsed follicular lymphoma like my wife has. Thanks for sharing.

Lymphomaniac said...

Thanks for reading! Yes, lots of treatments available, and lots more in the development pipeline. There are lots of good reasons to be hopeful for the future.