Sunday, March 14, 2010

Lenalidomide lets loose

In a word, brutal. That's how I would describe my first ten days of lenalidomide, aka Revlimid.

I took my first 10 mg dose on Thursday, March 4. For the next two days the main symptom was fatigue, which is common among those starting the drug. It was nothing insurmountable, but it did require an extra hour or two of sleep at night and a nap during the day. (I took the pill at bedtime, which is recommended.) Waking hours were accompanied by a certain amount of cat-like lethargy, but I was still able to work at my home business. I would not want to be starting Revlimid while holding a high-pressure job or managing a busy household. This drug is the enemy of multitasking.  

By Saturday I was starting to feel noticeable effects of tumor flare, which is where the brutality comes in. It seemed as if my lymph nodes (and probably spleen) were growing by the hour. My abdomen became so distended that I looked at least eight months pregnant. A baseball was developing under my right arm. By sometime Sunday my neck was wider than my head. I could barely button my largest pair of pants. I was eating less because I was feeling full faster -- my spleen was probably pressing on my stomach and the abdominal bloat was pushing up from the other direction. I would say that in a matter of just a few days my lymph node bulk increased by at least 50%, and that's just a rough guess. It could have been upwards of 100% in some areas.

Each nightly pill added fuel to the fire. It seemed as if the nodes were intent on growing whether there was space for them to do so or not. While I knew that tumor flare is a normal side effect of lenalidomide, it was still scary. It provided me with a snapshot of how much worse my chronic lymphocytic leukemia could get if things got that much more out of control.

By Sunday evening I was experiencing a new symptom: trouble getting a deep breath. Up until then I was willing to tough it out, despite the discomfort. Bloated, distended, ready to give birth to an alien baby, that I could handle. Shallow breathing, not so much.

The shortness of breath was not constant, nor was I feeling like I was going to pass out. I was getting enough oxygen. But it was disconcerting, to say the least, and it was becoming more frequent the longer I stayed on the drug. Perhaps a mass of nodes was pressing on my diaphragm, or perhaps nodes were interfering somewhere else with the breathing process, or perhaps both. I couldn't help but wonder how much worse it might get.

I should interject here that, according to studies, tumor flare can crop up anywhere from 0 to 56 days after starting Revlimid. Median time to resolution is 14 days. I was just four days in.

By Monday night I had the intuitive sense that taking more Revlimid had the potential to push me into the realm of unintended consequences. I considered using steroids to dampen the inflammation since ibuprofen had proven worthless -- both ibuprofen and steroids are  accepted methods of managing tumor flare -- but steroids also interfere with the ability of Revlimid to prod an immune response to the CLL. So it seemed somewhat counterproductive to start down that road, and I had no idea how long it might take for steroids to begin to work effectively.

Ultimately, I decided not to take the drug. I checked with my doctor on Tuesday, and on her advice I didn't take it that night, either. The shallow breathing actually worsened on Tuesday, to the point that I curtailed most physical activity. I didn't feel an improvement of symptoms until Wednesday, especially later in the day, a few hours after I had my weekly 1000 mg dose of oftatumumab.

I met with my doctor that day -- try holding an intelligent conversation a half hour after you have gotten 50 mg of intravenous benadryl -- and we decided to temporarily scale my Revlimid dosage back to 5 mg. Since then, the tumor flare has continued to abate.

There is some debate about whether tumor flare presages a better response to the drug. A report issued by Celgene, the drug's maker, summarizing the findings of various studies, put it this way:

"There have been conflicting reports regarding the association of response to therapy with the occurrence of tumor flare (TFR) symptoms. Padmanabban et al. reported (2006) that TFR may be associated with clinical response and Coleman et al. reported (2008) that [in] four CLL patients, symptoms of TFR signaled a response. Sher et al. also stated that the occurrence and severity of TFR appeared to correlate with clinical response (2009). However, Ferrajoli et al. reported that, in their 2008 study, TFR did not predict for a higher response rate, but did develop more frequently in patients with lymph nodes >5 cm compared to other patients (53% vs. 15%)."

So, ultimately, there is no way of knowing for sure whether my lymph node explosion was a good thing. There's also no way of knowing whether cutting it short was a good or bad decision CLL-wise, although it certainly was the right call breathing-wise. If you can't breathe, CLL is a moot point.


CLL CANADA said...

Thank you for sharing this with the CLL Community, David.

First had accounts like this are vitally important in my view and I will place a link on my web side to this article.


Anonymous said...

Hi David,

I was struck by your ultimate decision to follow your intuitive sense. It's obviously not a fool-proof weather-vane pointing toward correct action, but I think it's the best available to us. During my own treatment I disobeyed my doctor's orders to continue chemo even though I was getting sicker by the day with some kind of flu. At that crisis point I could not justify to myself the risk of continuing to assault my immune system with more chemo when I felt deep down that the illness was close to taking me to a place I didn't want to go. I discontinued the chemo regimen for a few days until I could feel myself starting to rally. It clearly didn't hurt me any, since I've now been in complete remission for over ten years.


Anonymous said...


Well, sorry to hear you've had a rough time with the treatment and thanks for sharing it. You've probably done the right thing by cutting the treatment short - it sounds worse that you couldn't breathe properly!!! Sometimes we have to go against medical orders - I think you did the right thing.

Denny, great that you have been in remission for 10 years!

kind regards

Anonymous said...

Hi, David: I have been in a Revlimid trial (non-pre-treated; no other meds) for over two years. I was surprised that your doctor put you on 10 mg to start. This is the highest limit of our trial, and all patients are started at 2.5 mg and slowly brought up to 10 mg unless symptoms preclude. We were also prescribed allopurinol to deal with the effects of the tumor flare. I have been on 20 mg for the past several months. My tumor flare abated early-on, but was nothing like what you experienced. Thanks for sharing your experience, and I look forward to reading more of your blog.

tim thompson said...

Thanks David. That is food for thought as we seek our best path to take. Oddly, I've had all those symptoms without benefit of revlimid. Only thing that eventually helped was radiation.

Tim Thompson
Owen Sound Ontario Canada

Deb Light said...

Thanks David for writing of your Revlimid experience.Sorry you had so many problems with it.Some Doctors say not to go over 5mg. of Revlimid.Every Doctor is different though and how everyone responds is different.Hope you can continue with the Revlimid at a lesser mg.Is there a 7.5mg one available?

Thoughts and Prayers,

David Arenson said...

There have been trials of Revlimid at varying dosages in CLL, the highest I'm aware of being 25 mg. Based on these studies, Celgene recommends an upper limit of 10 mg daily for CLLers. We are following the MD Anderson ofatumumab and lenalidomide protocol, which calls for 10 mg. But we went in knowing that we may need to make some adjustments.

I am taking allopurinol daily to guard against tumor lysis. So far my weekly CBC and chem panel have shown nothing unusual.

Bobby Golden said...

Dave, hang in there my friend. I just got done with 6 cycles of rituxin and methylprednisolone in Dec. 2009. Had an MRI last week to check for node progression. And YES an Mri with contrast will highlight swollen nodes so ask for one in the future instead of a ct-scan(which gives off too much radiation). We definitely dont want any secondary cancers. Due to a new progression of ab lymphnodes, I will be going back in next month for some more treatments.. Sincerely, Bobby Golden

carlin said...

David, Do you mind if I email you personally? My I have your email? This is Carlin Camp, we emailed before, I have a question,please.
Thanks so much,

David Arenson said...

Hi Carlin.

I have enabled my email address -- click on "View My Complete Profile" on the right-hand column, opposite the picture of Obama dressed as a doctor. There will be an "email" link on the profile page on the left.

Look forward to hearing from you -- It's been awhile!



Anonymous said...

My friend is about to start revlimid and we want to know about whether insurance will pay for it. how did you all manage the very high cost?

David Arenson said...

I qualify for assistance from Celgene, the drug maker. As I have a low income, I meet their test for providing the drug at no charge.

Some steps were necessary first. My doctor applied for insurance to cover Revlimid. They denied it. The doctor appealed and they again denied it. This made me eligible for Celgene's Rev-Assist program.

You can find more information on Rev-Assist online.