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Campath (#1)

Posted by Frederick Wasti
Dec 13 2012

I would like to devote this post to Campath, the monoclonal antibody that I first started taking during Part B of my clinical trial. If the name seems new to you, it probably is because I have usually referred to it throughout Part B, and now into Part C, using its generic name of Alemtuzumab. Now, that will likely sound more familiar to you - <smile>. (I actually have used the brand name of Campath a few times, but usually only just parenthetically.)

I should point out that it seems as if I always have to be familiar with at least two names for every drug -- there is generally a trade name (or two) and there is also a generic name for each drug, and often both names are quite commonly used. For example, especially in Part A, I received high doses of the steroid Methylprednisolone (with occasional lower doses in Parts B and C), and at D-F it is sometimes called just that (which is its generic name), or maybe "Methylpred" for short,...

...but sometimes it might also be called Solu-Medrol, or Su-Medrol, which are two of several trade names for it...

 

Similarly, the first clinical trial monoclonal antibody I received is most often referred to generically as Ofatumumab, but it might also be referred to at D-F simply with the nickname of "Ofa", or as Arzerra, which is its trade name.

Well, at D-F, Alemtuzumab is most often referred to as Campath (which is certainly easier and quicker to say). However, when a syringe full of Campath arrives at my infusion chair for injection into me, the label will say "Alemtuzumab" on it (and it will not say "Campath"), and my infusion nurse and a second infusion nurse (and at D-F ~two~ nurses are always required to check such a drug before it can be administered) will both check it for its identity and its quantity (and my identity, too, but fortunately not my quantity - <grin>) using the name of "Alemtuzumab" - they will read "Alemtuzumab" on the syringe label, they will read "Alemtuzumab" on the paperwork that they both have to sign, and they will say "Alemtuzumab" out loud when confirming to each other just what I am about to receive. Still, at most other times, the D-F personnel will use the "easier" name of Campath.

Campath has a history that goes "way back" to 1979, when it was first synthesized by Herman Waldmann while working in the Pathology Department of Cambridge University in the UK. (At this point, you may have just figured out why Campath is called "Campath" - it was a product of CAMbridge University's PATHology Department - <smile>.) Now, you might be thinking that 1979 is not exactly "way back" in history at all, but, in the history of the development of monoclonal antibodies, it really is -- in 1979, experimental work with developing MABs (as monoclonal antibodies are often called for short) was indeed still in its infancy.

What Campath does that makes it useful for treating CLL patients (especially those of us with a 17p deletion in their CLL cells) is that it kills leukemic (and, unfortunately, also normal) B-lymphocytes (but is not dependent on having unmutated #17 chromosomes to do so, unlike most other anti-CLL agents). Campath attaches itself to the CD52 protein antigens on the surface of lymphocytes, and, when it does so, this ends up starting a process that destroys such cells. (If you're a bit vague on the significance of the CD molecules on the surface of blood cells, you might check out my previous blog entry on "How Monoclonal Antibodies Work" from 9/2/2012.)

You may remember from earlier blog entries that Ofatumumab and its more frequently used competitor, Rituximab (trade name Rituxan), kill B-lymphocytes similarly (although not identically), but they attach themselves to CD-20 molecules, instead of CD-52 molecules. But, since CD-20 molecules are found only on B-lymphocytes, and since CD-52 molecules are found on both B-lymphocytes and T-lymphocytes, Ofatumumab and Rituximab will kill only B-lymphocytes, which are involved in CLL, but Campath will kill both B-lymphocytes and T-lymphocytes, even though T-lymphocytes are not involved in CLL at all, so it turns out that Campath does cause greater "collateral damage". However, Campath does a remarkable job of killing B-lymphocytes in the bone marrow, which is something most other anti-CLL MABs are not quite as good at - the CD-20 MABs tend to work well in the bloodstream and to some extent in the lymph nodes and spleen, but not quite as well in the marrow, which is where Campath really shines.

Just for an example of the power of Campath at destroying lymphocytes, let's take a quick look at how the absolute number of lymphocytes in my blood have declined during my clinical trial:

Notice that, during Part A, my lymphocytes dropped gradually from almost 50,000 per cubic microliter down to about 2,000 per microliter, but, immediately after Part B started, just two days later, they had dropped from 2,000 to only about 40 lonely lymphocytes per microliter. Because of the scale of the graph, this difference may not be totally apparent, but, let's take a look at how the percentage of my white cells that were lymphocytes varied during the trial:

Here, even if I hadn't labeled the "Start of Part B" (which is when I first began receiving Campath), I'll bet you could probably guess as to where it is on the graph. In just two days, my lymphocytes plummeted dramatically, from about 35% of my total white blood cells to only about 1% of my white cells, and the percentage has remained in the vicinity of 1% ever since. Such is the power of Campath.

Interestingly, though, it was the fact that Campath destroys T-lymphocytes (in addition to B-lymphocytes) that caused it to be first tried as an aid during bone marrow transplants in 1982. It was known, even at that time, that transplants too often failed due to the recipient's T-lymphocytes' proclivity to attacking the donor's cells, so Campath was tested in a very small number of cases to see if its depletion of T-lymphocytes would help prevent rejection, but the results of these experiments were mixed.

However, starting in 1985, Campath was also tried on very small numbers of CLL and Non-Hodgkins Lymphoma (NHL) patients and, although the results were also mixed, they did appear more promising than the results from the transplant experiments (and more so for CLL than for NHL). Shortly after the CLL experiments had started, Campath was also tried with some success on several different auto-immune diseases that involved T-lymphocytes, and with some success, although one of the disappointments was that patients with Rheumatoid Arthritis (RA, an auto-immune disease, quite unlike the more common osteoarthritis that I have) did not respond very well overall.

In the early 1990's, there were some interesting experiments run on a number of persons having Multiple Sclerosis (MS) that did provide some encouraging results, and even some of the failures provided researchers with new insights into just what may cause MS to progress. However, I will have more to say about the use of Campath in treating MS and CLL in the next blog entry - so please stay tuned...

Categories: Leukemia