Topics Alert

Prophylaxis: Do It Right — Take the Necessary Precautions Ahead of Time

Date: August 12, 2024

Chemoimmunotherapy is pretty hefty stuff. If you are ready to bring in these big guns to fight the CLL, it is important that you do it right. I don’t know about you, but I tend to be the belt-and-suspenders kind of gal when it comes to protecting my guy from possible side effects of chemoimmunotherapy.

I thought I would bring you folks up to speed on how “Harvey” is doing with the HuMax-CD20 + fludarabine (HF) combination. As you know from prior “Harvey” articles on our website, our hypothetical hero developed hypersensitivity to Rituxan, hence the combination of HuMaxCD20 + F, rather than the more familiar Rituxan + F. No one has done the HF combination before: Harvey is the first one in the whole world of CLL patients to be trying this specific combination. We hope it will be even more effective than RF, since H seems to be somewhat better than R, when the two monoclonals are compared as single agents. However, fludarabine is the common factor – and it brings with it the familiar package of adverse effect risks. I hope I never hear from yet another CLL patient that came down with a bad case of shingles after treatment with fludarabine-based therapy without protection. Believe me, post-herpetic pain from shingles infection can make even very macho men cry – it is not a pretty sight.

Harvey has finished his first course of HF, without incident. He received 2,000 mg of HuMax-CD20 (this seems to be the “standard” dose the company is going for. It is the dose they are using in many of their clinical trials) on day 1. He got the fludarabine on days 2, 3 and 4, at a dose of 30 mg/m². Pay attention to the units, the mg/m² uses your individual body size to calculate the correct dose. If you are not familiar with the concept of measuring your Body Surface Area (“BSA”), please click on the link at the bottom of this Alert and read all about it.

Harvey is on daily prophylactics, starting with the first day of the first cycle of fludarabine therapy. Here is the laundry list:

1. Bactrim. This is a broad-spectrum antibiotic that is given to protect him from a variety of nasty bacteria out there. Did you know as many as 10-15% of CLL patients undergoing purine analog therapy (fludarabine, pentostatin, cladrabine) are at risk of developing pneumonia? Pneumocystis carinii (PCP) is one of our biggest enemies. Pneumonia and other pulmonary infections are the single biggest cause of death in CLL. Given proper broad-spectrum antibiotic protection, the risk of pneumonia during fludarabine therapy goes down next to zero.
2. Valacyclovir (“Valtrex”). This is an anti-viral medication, to protect against a variety of herpes infections. Both Valtrex and its analogs (famcyclovir – “Famvir” is another one) have been used extensively in the past few years as daily medications to prevent recurrent genital herpes. These anti-virals are also effective in reducing the chance of shingles, caused by the varicella zoster virus (Herpes Zoster), the virus that also causes chickenpox.
3. Fluconazole (“Diflucan”). This is an anti-fungal agent. CLL patients undergoing fludarabine therapy quickly become depleted in T-cells, and these powerful cells of the immune system are our primary defense against fungal infections. You do not want to deal with candida (a type of yeast) infections (oral “thrush”) while you are also battling CLL and chemotherapy.
4. He is also on daily vitamin D₃ supplementation, to counteract sun avoidance. CLL patients are at increased risk of skin cancer, especially during and immediately after fludarabine (or any other T-cell depleting) therapy. We wrote several times about the value of this important vitamin in protecting us from a variety of infections. Look them up if you are not familiar with the subject.

The game plan is that Harvey will be on these daily medications until he is done with the last cycle of HF. He will then be tested for T-cell counts and get off of the meds once his T-cell counts have recovered sufficiently.

I have deliberately not included his dosage levels. I don’t want any of you to think we are in the drug prescription business here, we are not qualified to do that. You have to talk to your own healthcare providers to determine the dosage. Also, some people are allergic to one or more of these drugs, in which case you have to be given an appropriate alternative. The reason for my sending out this alert is that I have heard from two patients in the last two days whose local oncologists told them protective medications are not necessary for fludarabine therapy. I beg to disagree. And I backed up my understanding on this issue by getting feedback from more than a couple of world class CLL experts, before “Harvey” got started on HF therapy.

One last point to remember: fludarabine does a pretty good number on neutrophils. Now, if you pause to think, CLL patients are a tad low on protective immunoglobulins (“Ig”) as it is and fludarabine kills T-cells, the second arm of the immune system. B-cells are shot anyway, whether or not they are cancerous CLL cells. What does that leave us by way of protection? Neutrophils. So, you can imagine, getting neutropenic and not doing anything about it is not a good idea. Patients generally hit bottom (“nadir”) on their counts about week to ten days after fludarabine. It is a good time to check the CBC and see how the neutrophils are doing. If they are low, and don’t seem to be staging a recovery when the CBC is checked again in few days, intervention is required. Harvey was prescribed daily Neupogen shots until the neutrophil counts came back into the normal range. This was also considered important to keep him on schedule for the next HF cycle, since fludarabine is contra-indicated for patients whose neutrophil counts are too low.

So far, so good. One cycle done, another one about to start, four more to go after that. Then on to a cord blood transplant. Please wish Harvey luck.

BSA;
Vitamin D₃;
Pulmonary infections in CLL;
Chronic inflammation and what you can do about it;
Infectious complications - Best Practices;
Who is most at risk of infectious complications;
Topics Alert #108: Fludarabine Therapy Increases Risk of Skin Cancer.

Be well,

Chaya
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