Decision theory

To tux or not to tux: that is the question.

Rituxan (trademark name; generic is rituximab) is a monoclonal antibody. "Monoclonal" simply means that the antibodies are identical (cloned). These artificially produced antibodies bind to the CD-20 protein complex on the surface of B-cells, including hairy cells. This dupes the immune system into thinking those cells are foreign, so it attacks them, with the same responses it would deploy against invading bacteria.

The drawback: rituxan can't discriminate between normal B-cells and hairy cells. It's genocide; the stuff just kills them all (or rather, it paintballs them and leaves your own body to do the dirty work on itself). Then the body grows new B-cells. You hope, you pray, that the new population doesn't include any hairy cells, or at least not so f-ing many.

In HCL, rituxan doesn't work very well all by itself. 8 weekly doses does markedly better than 4, but the response rates using rituxan alone, in previously untreated patients, are nowhere near as good as 2-CdA. But what about a combination of the two?

Those of you who've followed this blog may remember that early on, I considered enrolling in a clinical trial now underway at MD Anderson in Houston. They're testing a regimen of 1 week 2-CdA + 8 weeks of ritux starting 28 days later. In 13 patients treated with this regimen,

the CR rate was 100% with eradication of MRD (minimal residual disease)... in all but 2 patients after completion of the sequential therapy. No additional toxicity was observed with the combination compared with historical experience with 2-CdA alone (Hematol Oncol Clin N Am 20 (2006) 1125–1136).

That sounds pretty exciting, but it's only 13 people. Statistically, 2-CdA alone would have produced 9 or 10 CRs in a group that size anway. Still, if this trial works out, this regimen might become the new front-line therapy in a few years. If I do 8 weeks of rituxan now, my treatment would be almost clinically equivalent.

Let's be realistic here: this is not aspirin. My HCL friends haven't experienced serious side effects, apart from the few hours during and after the infusion (see Experience). But bad stuff does happen. Patients have died from cardiac arrest and kidney failure. A small number — all of them already suffering from lupus — came down with progressive multifocal leukoencephalopathy, a horrifying virus that kills brain cells and, eventually, you. You can get pulmonary toxicity and other nasty effects. However, most of the patients who've used this drug were being treated for other leukemias and lymphomas (not for HCL), so they were a lot sicker than I am and thus more likely to suffer side effects. Still, the reality of risk has to be faced. (That sentence sounds a lot nicer in passive voice.)

So here's my decision theory, so far.

Reasons to tux:

• A good-to-excellent chance of achieving complete remission (less than 1 percent hairy cells).
  
• A fair-to-good chance of achieving complete molecular remission (no detectable hairy cells).
• If I'm gonna do it, now's the time. Ritux doesn't do well once the population of hairy cells gets larger. If I wait, I'll have to do another round of 2-CdA before I can get much benefit from rituxan. On top of that, I have the flexibility in my life and schedule right now to do the treatment without drastic effects on my job and my family.
  
• A fair-to-good chance of a CR lasting 5 years or longer. New, better, more targeted drugs might be ready by then. If they are, I might not have to drag my body (and my family, and my friends, and you) through another round of 2-CdA.

Reasons not to tux:

• In HCL, the relationship between the degree of remission and its duration — the time until symptoms reappear — is not straightforward. I'm at 5-10% hairy cells now. It's entirely possible I could stay this way for 2-4 years, or more, without treatment. Conversely, even if I achieve a complete molecular remission, the HCL could still come back in less than 5 years.
  
• Immediate risks from rituxan infusions.
• Longer-term rituxan side effects. I'm still coping with daily post-2CdA headaches (see my blog entries from January). Headaches are a low-grade side effect, not life-threatening; the medical literature barely tracks them, so there's no real way to know if the 2-CdA might have caused them. (In higher doses than I received, 2-CdA is neurotoxic, hence my suspicions.) Rituxan might make them worse, or slow my recovery, or both. Can't know in advance.
• What WAID and John said, about not doing a treatment just to get nicer numbers, and about handling HCL as a chronic disease.
  

Seeing Dr. B tomorrow. My main questions for him: what's your clinical experience with rituxan? Side effects? What's the timeline for the other drugs now under development? What do you think of their chances for success?

And most of all — if you had HCL, what would you do?