Onward and upward with Revlimid

At the end of my last post, I posed the question of what to do about my Revlimid dose, which is providing stable disease at 10 mg per day. 

Do I accept that as the end point and maybe even step it back a bit if stable disease can be maintained at a lower dose? (After all, we really don't know what Revlimid is doing to my body, and what its long-term effects will be.) 

Or do I increase the dose in the hope that the more drug I take, the more effective it will be? (After all, we are dealing with CLL here, and knocking it back is worth the risk, which may turn out to be small given Revlimid's history in CLL so far.)

Run this question by one of the leading experts on CLL and Revlimid and the answer is: Bump it up.

And so, for almost two weeks now, I've been on 15 mg of the stuff.

I have a friend who is in a clinical trial at New York's Roswell Park Cancer Institute, where Dr. Asher Chanan-Khan is the principal investigator, and where the clinical nurses also know more than a thing or two about Revlimid and CLL. Chanan-Khan and his staff have been doing Revlimid (aka lenalidomide) trials for several years and probably know more about its effects on CLLers than anyone else. This fellow patient kindly agreed to run my case by the powers that be. 

The patient is in a trial for untreated patients, in which participants are stepped up to 25 mg at two week intervals, starting with 5 mg. Optimally, patients will then stay on 25 mg for six months, which is the level at which the best results have been seen. After that, patients will go into a lower dose Revlimid maintenance program. One patient has been in treatment for 52 months.

Some patients can't tolerate the drug, of course, and have to drop out. Others get good results at lower doses than 25 mg, so they are never bumped up all the way. There's a certain finessing that goes along with determining Revlimid dosages.

Ironically, the higher the dose, the easier the drug seems to be on most patients. Nurses report more problems in the beginning, with smaller doses, as the body gets used to the drug. My friend, who is now at 25 mg, reports that his experience bears this out.

Much to my surprise given my rocky Revlimid history of tumor flare and rash, my experience is bearing it out also. The only ripple is that I have experienced more tumor flare -- the usual, non-dramatic kind, nothing like I had in the beginning. This is understandable given the increase in dosage. Tumor flare is a good sign, according to Dr. Chanan-Khan, who says it means the drug is working.

Chanan-Khan also thinks the Revlimid is doing most of the work in the protocol I'm on, which also involves periodic infusions of the anti-CD20 monoclonal antibody Arzerra (ofatumumab).

I discussed all this with my oncologist, and she agreed that bumping up the dose at two week intervals was worth a try so long as I can tolerate the drug. We'll continue with the Arzerra for the time being. So the original OL protocol has now been modified to reflect higher doses of Revlimid. One of the advantages of following a clinical trial from afar is that you can modify it if necessary since you aren't locked into a search for empirical data. Your primary concern is clinical results. 

My friend also has 11q-deleted CLL and has noticed progress with his lymph nodes as time has gone on and dosages have increased. At 5 mg and 10 mg some of his nodes became soft and squishy and at 25 mg he notices node masses separating.

Since nodes are my biggest challenge, I'm hoping for tangible progress as time goes on. I had some beginning in May, when a big node mass under my right armpit separated, but things appear to have found a plateau since then.

It's important to remember that Revlimid is an immunomodulator, not a traditional chemo drug, so progress will be slower and less complete -- but I hope significant enough in the course of time to keep the disease down without taking on the risks associated with fludarabine, cyclophosphamide, and the like.

Tomorrow, 20 mg. 

The Vitruvian Rat

The OL protocol after six months

It was six months ago to this day that I first downed a Revlimid capsule. Cheers! Salud! L'chayim!

I was embarking on the pill half of my latest CLL treatment protocol: Arzerra (aka ofatumumab), the anti-CD20 monoclonal antibody; and Revlimid (aka lenalidomide), an immunomodulator. I call it the OL protocol.

As readers of this blog know, I had my challenges with the Revlimid: tumor flare, rash, fatigue. It's not a fun drug. My body got used to it, but I'm not sure I have. 

I'm just about to end a week-long, doctor-approved Revlimid treatment holiday. The OL protocol has me slogging through 10 mg of the stuff every day. In myeloma protocols, and in at least one CLL clinical trial that I know of, patients get three weeks on and one week off. During this week off I have slowly seen the drug-induced fatigue and dullness leave my body. I have more energy again and I'm mentally sharper. Revlimid subtly but surely detracts from certain aspects of quality of life. So the results had better be worth it.

Are they?

The results so far have been mixed, a combination of disappointment and relief, and might technically be considered to be "Stable disease Plus."

The disappointment has been in the lymph nodes, where most of my 11q-deleted disease resides. Back in May I thought I was finally having some luck in that department. But rather than presaging progress to come, it turns out May's results were an anomaly. Further treatment has not yielded any more progress. The nodes are pretty much where they were when I began. 

Which is to say they appear to be (with the naked eye and roving hands, as opposed to an abdominal CT scan) stable. While I was hoping for more, I have learned after seven years of fighting this thing to be content with treading water. It beats drowning.  

Nodes, like facts, are stubborn things, at least in my case. The only thing that will really blast them -- and I'm not at all confident that it would get rid of them completely -- is heavy-duty chemo. Steroids provide a nice reduction, but it is fleeting. The addition of cyclophosphamide provides a longer reduction, but not that long. FCR would probably do better, as would R-CHOP or the like. But the results would last how long? It's best not to take that sort of step unless I really have no other choice, and unless I'm prepared to roll the dice on a transplant afterward. But it is also best not to let the nodes get any worse, which means that keeping them stable, while not optimal, is important.

An area where the protocol has worked has been in the peripheral blood. My absolute lymphocyte count has been "normal" for months now, dropping from 11.8 on Feb. 23, the day before the protocol began with my first Arzerra infusion, to 3.2 as of last week. In clinical terms this means absolutely nothing. The blood is not where the disease is congregating. 

I have also been spared the neutropenia and thrombocytopenia that can accompany the protocol. My platelets, which have slowly dropped over the years, landing in the 120s a couple of years ago, have remained stable.

The really good news -- and the "relief" I mentioned above -- is that there has been no sign of autoimmune hemolytic anemia (AIHA) since I began the OL protocol. On the quality-of-life scale, dealing with sudden bouts of severe hemolysis of red cells has been the bane of my existence since the first incident occurred in early 2007. Over the course of time I became refractory to more and more AIHA treatments, including steroids and Rituxan. It was even getting to the point that the RCD protocol  (Rituxan, cyclophosphamide, and dexamethasone) was only holding me for three months.


Here I am, six months later, with normalized red counts, hemoglobin testing in the 13s and 14s, and no signs of orange pee or pounding in my ear. I can't leap tall buildings in a single bound, but I can at least climb the stairs with ease.

I am thinking that the Revlimid, doing its immunomodulating thing, is probably responsible, or primarily so. I had already become refractory to Rituxan, and Arzerra is a cousin of that drug. Dr. Chanan-Khan, the CLL Revlimid research guru, told me that he knows of two actively hemolysing patients whose situations were turned around when they were given Revlimid.

The take-home message to all of you fellow AIHA-ers is: Consider Revlimid.

This is the big "Plus" in "Stable disease Plus" and -- along with maintaining evident stability of the nodes -- is a big reason why I will continue to take the drug and work with the protocol. My doctor and I are discussing ways to tweak it or change it, given that it appears I will have no more progress with the nodes the way things are. The question is: What is the minimum dosage I need to maintain stable disease and keep the AIHA in its box? And another question: To what degree is the Arzerra contributing to this stability? And of course: Will upping the dose of Revlimid give better results on the nodes?

There are always more questions than answers in CLL.