CAL-101... A week later

I had my second infusion of rituximab yesterday at Stanford. I'm happy to report that the infusion went well; no vomiting and no chills, as happened a week ago. My GERD is back; I assume this is due to the vomiting and/or the rituximab infusion.

My blood numbers were interesting. Since my disastrous bout with FCR, my counts have been very low, with the WBC ranging from 2100 to 2700 or so. This time, my white count is over 44,000. This fits with what I've learned about CAL-101, and also fits with my sudden and unexpected shrinking of my lymph nodes. The thinking is that this kinase somehow pushes CLL cells out of the lymph nodes and into the circulatory system, where it can be detected by a simple blood draw.

The rest of the numbers are about what I've been living with for the past few years. My hemoglobin count is a bit lower, from the high 12s to the high 11s. My platelets, though, are much higher. They've been hanging around the 90 neighborhood; now they are over 140, and in the normal range. This is the first time that's happened in years and years. In fact, I can't remember when it was in the normal range.

My absolute lymphocyte count is high, as one can imagine. My absolute neutrophil count is also up substantially, which is very nice. Dr. Kipps has been puzzled by the low neutrophil counts over the past two years, which have nevertheless not led to a single serious infection. He thought that maybe the neutrophils were 'hiding out' in the tissues somewhere. It appears that he was right.

I am taking 150 mg of CAL-101 twice a day since Wednesday of last week. It's not a difficult thing to remember, and I'm home in the morning and evening. I'm back on acyclovir and Septra, the first to forestall herpes infections, and the second to help prevent bacterial infection, primarily in the lungs.

I'm carrying on my normal activities, which include having a sewer and water line replaced at my rental house, and doing some painting and other minor repairs. I'm trying to stay away from sick people, crowds, and soil fungus.

So far, so good.

CAL-101

I have made the cut, I guess you could call it; I'm now in the Stanford CAL-101 trial, combined with rituximab.

This is a trial of weekly rituximab infusions, for eight weeks, combined with 150 mg of CAL-101 twice a day. The CAL tablets come in a prescription bottle, with a seal and, yes, even cotton at the top of the bottle. The nurse said that they have a drug company bottle the CAL for Calistoga.

I went in for imaging on Tuesday and Wednesday of this week; I had the CAL that afternoon, followed by 375 mg/m2 (the usual dose). I've had seven rituximab infusions before, with no problems.

This time was different. I don't know if it was the long day (up at 5:30 to get the MRI by 7:00), the MRI contrast (I was in that darn machine for over an hour), the CAL, or what, but at the 7/8 mark, I started to get nauseated. Yep, I threw up my day's gorp trail mix, bananas, and Gatorade is a disgusting mix. Two sets of multiple vomiting episodes. The first I didn't quite make it to the bathroom. I tried to hold it, but dragging a IV pole along for the ride didn't help. (I'm sorry, Ms. Housekeeper. I really am.)

I felt pretty rotten. I also got a bit chilled, but my blood pressure and temperature held at the normal level. I tried to tell the nurse practitioner this, but she was very Nurse Ratchet about the whole thing and stopped the infusion. I told her I didn't feel good and wanted to go home (home being a three hour drive). We compromised with her re-starting the infusion, and me promising to stay the night (at another $112) in super-expensive Palo Alto. (BTW, near Stanford, the lodging is even more expensive than La Jolla!)

The nurses made the reservation for me, which was really nice. I'm sure my green complexion motivated them, and since it was after 8 pm, they wanted to go home as badly as I did.

I got to the motel, locked the door, turned the heater on full blast, and promptly fell into a very deep sleep for five hours. I even fell asleep before I could floss and brush my teeth.

I felt much better when I awoke, though I had a splitting headache. That vanished by late morning. I putted around the motel (actually I watched an episode of The Sopranos. I've never seen the program, because I'm very put off by violence). This was on USA or some other network, so some of the violence was cut out. Still more violent than I wanted, so I changed the channel.

It's late evening, and I feel OK. However, with rituximab, I now need to be extra careful about avoiding infection. My numbers have been OK the past six months or so, and I've gotten out of the habit of being really vigilant. That has to change. Bummer.

Rituximab Isn't Sugar-Water

Many CLLers use rituximab to treat their CLL. It is preferred to chemotherapy drugs such as fludarabine because it seems by comparison to be relatively non-toxic (except, of course, for the acute infusion reactions).

This paper in Blood points out the chilling fact that rituximab has been linked to a serious brain disease, progressive multifocal leukoencephalopathy (PML).


Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project

Kenneth R. Carson, et al

Rituximab improves outcomes for persons with lymphoproliferative disorders and is increasingly used to treat immune-mediated illnesses. Recent reports describe 2 patients with systemic lupus erythematosus and 1 with rheumatoid arthritis who developed progressive multifocal leukoencephalopathy (PML) after rituximab treatment.

We reviewed PML case descriptions among patients treated with rituximab from the Food and Drug Administration, the manufacturer, physicians, and a literature review from 1997 to 2008.

Overall, 52 patients with lymphoproliferative disorders, 2 patients with systemic lupus erythematosus, 1 patient with rheumatoid arthritis, 1 patient with an idiopathic autoimmune pancytopenia, and 1 patient with immune thrombocytopenia developed PML after treatment with rituximab and other agents. Other treatments included hematopoietic stem cell transplantation (7 patients), purine analogs (26 patients), or alkylating agents (39 patients).

Median time from last rituximab dose to PML diagnosis was 5.5 months. Median time to death after PML diagnosis was 2.0 months. The case-fatality rate was 90%. Awareness is needed of the potential for PML among rituximab-treated persons.

http://tinyurl.com/ofyubj

The other great disease which causes immunosuppression of course is AIDS. These patients can be struck by reactivation of the JC virus. It seems less common in CLL patients, at least it is not described in the literature to any great extent.

You don't want to get PML. It is caused by the JC virus, which is present in almost all adults. It lives in the body, harmlessly, for years. In cases of immunosuppression, occasionally it will attack brain tissue, leading to gross mental deficiencies, and in most cases, death. See the wikipedia article on the JC virus:

http://en.wikipedia.org/wiki/Progressive_multifocal_leukoencephalopathy

It should be noted that since all CLL patients are immunosuppressed, the disease may strike with or without rituximab. However, those using rituximab seem to be at a higher risk of developing the disease. Cases of PML were probably 'hidden' in the general population of immune-deficient patients such as those with CLL, so it was not clear and evident. In those with other diseases who are not immunocompromised, these cases are so atypical as to be suggested to be caused by the rituximab.

Still Waiting

I'm waiting for approval of my MRI imaging studies before I can enter the FCR+lumiliximab trial at UC Davis. The trial coordinator is Dr. Tuscano, who was nice enough to speak before the Sacramento CLL patient's group in 2006. He has been working on his own antibody, but I've not heard whether anything will come of it. It looks to be a less than rousing success, but the delays may be due to funding or other administrative problem.

So I'm in a holding pattern, in more ways than one.

One development is that I'm going down to UCSD to see either Dr. Kipps or Dr. Castro. We will see what is happening with my run-away CLL. I am less than happy with the skyrocketing counts that are not, so far, really apparent except in my large abdominal nodes. I don't feel any changes, still working full time and in the evenings seven days a week. Haven't been back in the mountains since I'm now anemic and I don't want to give myself a heart attack by hiking. Energy level has been dropping, but I'm sleeping fairly normally.

Lumiliximab is a CD23 antibody. CD23 is not expected to be a slam-bang MoAB like rituximab for the simple reason it doesn't seem to has as much killing power.

The most recent study and the reason I think Dr. Kipps has recommended this study to me is that the complete remission rate is almost 50% in previously treated patients, which is a very good result. Overall response rate is 95%.

There are two arms to the study, and you don't know what you are getting into before you sign up. You do know once the treatment is underway, so I will get at least one FCR course if I am accepted into the trial. I have more negatives (low platelets, etc.) than I did before trial number one and two. The more things wrong you have with you, the less likely they will choose you to be in their sample. They do want a success, and some folks have been accused of 'cherry-picking' patients that they think will do well for a particular trial.

It's such a game; a game with deadly consequences for the patient, at least.

Takin' a break

I'm obviously informal since I am using an apostrophe instead of a 'g' in taking!

The weather has vastly improved. Last week was what Sacramento is famous for, hot weather! And it was hot, hot, hot! We topped out at 109 or 110, depending on where in the Sacramento region you are.

I bought a window air conditioner for the laundry room, for our semi-feral cat Mrs. Chippy. It was so terribly hot in the garage (the laundry room is the breezeway, sort of, between the garage and the house. It worked great! For $62, it was a bargain and it lowered the temperature into the 80s, a big relief from the 110 degrees it was probably in the garage. I'm going to keep the A/C there until summer is over in two months, and then put it away until next year.

On the topic: I've decided to take a break from CLL. I know that sounds odd, but I've had treatment in September, October and November 2006, and then again in May, '08. I had a partial remission from the HDMP+HDR (high dose rituximab), but relapsed quickly. I have terrible markers and no one, including me, was expecting me to last 10 years with this form of CLL. (It will be 10 years on October 1.)

My last blood numbers on June 19 showed a nice drop from my rapidly escalating WBC, and I feel pretty good, so, why not? I did see the local oncologist at UC Davis regarding the lumiliximab (randomized to 1/2 of the participants) trial. They remarked that they thought it was odd I'd be undergoing treatment when my performance level is '0' (zero, the lower number the better), working full-time, etc. So I took that as sort of a sign, maybe from God, to ignore the disease for a month. I'll have my next blood test on July 19, which is coming up fast. We will decide what to do then.

In the meantime, I am chugging away. My wife, who has severe asthma, is having trouble with our high temperatures and smoky conditions. Visibilities have been on the order of a mile or so. Terrible. You can see the smoke in the air, the sun 'sets' about 4 pm, and there is actually ash falling nearby. It has been a horrible year.

Note the sad loss of P.C., Chaya's husband, Tony Snow and others from cancer. This disease seems to take the best and the brightest, doesn't it? I don't have survivor's guilt, because I will most likely die from CLL unless something else gets me first, and it could happen in a hour, a day, or a week from now.

So, a short break from researching CLL, reading CLL blogs, thinking about the physiological nature of the disease, etc., is in order for me, and, I might add, richly deserved, at least in my opinion!