At last, progress on the nodes

“Good news, everyone!”

Fans of Futurama and its doddering professor and sometime inventor Hubert J. Farnsworth will recognize that expression and know the voice that goes with it. If I may take a little more liberty in the style of the good professor:

“The Lenalidomide-Ofatumumab Leukemi-o-meter De-noder appears to be working!”

Not all of Farnsworth’s inventions pan out, of course -– and not all patients get good results with the Revlimid (lenalidomide) and Arzerra (ofatumumab) protocol that I’m on. In its own way, the protocol is as chancy and experimental as Farnsworth’s inspirations often turn out to be in Matt Groening's sci-fi cartoon TV show.

More than one fellow CLLer has reported to me that our expert doctors, big names you’ve heard of, are intrigued by Revlimid but have no idea how it does what it does. (Farnsworthian indeed!)

For patients, of course, the bottom line is results. After struggling with Revlimid dosages, tumor flare, fatigue, and a rash during a three-month period and seeing very little progress, I have to admit that I was becoming a bit pessimistic. Even the Arzerra, an anti-CD20 monoclonal antibody -- supposedly better than Rituxan, to which I have responded in the past -- appeared to be a bust.

Like a mantra, I found myself repeating a fact to myself from one study: The median time to best response is 5.9 months. Or as a researcher with experience in Revlimid trials told a friend of mine: “If it doesn’t work within six or seven months, it’s not going to work on you.”

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The last thing I expected was that progress would be sudden. But it has been, like turning on a light switch. I alluded to it in my last post, which was mainly concerned with a Revlimid-induced rash that I had developed.

In the week prior to my May 20 monthly Arzerra infusion, I had finally managed to get my Revlimid dose up to 10 mg daily, which is what the protocol calls for. This obviously raised the levels of the drug in my body (ergo the rash). I began to suspect some subtle progress on the nodes in my neck. On Thursday the 20th, I had 1000 mg of Arzerra. Over the next four or five days, the switch went on. I began losing weight, and my neck and abdomen showed visible progress.

But the best example of change was the nodal mass under my right arm. What had been a hard baseball-like thing (well, half a baseball) -– a number of nodes that had grown together -– simply fell apart. I can feel individual nodes there now, but they’re no longer connected.

I’m making an educated guess that this could be going on in the abdomen, which has slimmed down considerably. I’m still full of nodes, but the masses may be breaking apart as each node reduces in size. My neck is looking positively scrawny as a mass on the right side has undergone a similar fate.

Why the Arzerra chose that weekend to kick in, I don’t know. To give my body a break from the rash, I was off Revlimid from May 20 until the night of May 24. But levels of the drug, which had been building while I was managing 10 mg daily, had to have been high on May 20, the day of the Arzerra infusion. Revlimid is an immunomodulator and perhaps it had sufficiently started to change the microenvironment in which my CLL cells live and my immune system functions, creating a more advantageous environment for the Arzerra. That's only a guess. (If the experts don't know how it works, I don't think I'm going to figure it out.) Whether that modulation has do to with dosage levels or length of time used, I can’t know for sure, although it stands to reason that both are a factor and that dosage is important.

That’s why I am anxious to get to and stay at the optimal dose of 10 mg daily. We all respond differently to drugs and their dosages. A tiny dose of vincristine, which probably would have gone unnoticed in another patient, once gave me peripheral neuropathy for months. Claritin, the allergy medicine, doesn’t work for me at all at the recommended dose. If I exceed that dose and take two Claritin, it does work. So in the case of one drug I am more sensitive than average, in the case of the other I am less so.

Revlimid in CLL is still a work in progress. But studies tend to indicate, and my own anecdotal experience suggests, that the higher the dose of Revlimid on average, the better the response. I surmise that CLLers on Revlimid should be on as high a dose as they can tolerate, 10 mg being the limit recommended by the drug’s manufacturer, Celgene.

* * *

Meanwhile, back at the rash . . . To control the rash, I began taking 4 mg of dexamethasone every morning starting May 25. The plan was to do 10 mg of Revlimid every other day and use the steroid to control the rash, easing myself up to adding 5 mg and later 10 mg on the “off” day.

At first, the steroid would work for much of the day, the rash only starting to return to my belly at night. After about four days, it began to work better. I’m now taking 5 mg of Revlimid on the “off” day and the dex seems to be able to control the rash over a 24-hour cycle.  Another couple of goes at 10-5 and I’ll try 10-10; if the rash remains under control, then I’ll stop the steroid, perhaps reducing it to every other day at first.

* * *        

Since I am on a steroid now, that does bring up questions about what role it may or may not be playing in my node reduction.

First, it must be remembered that the cascade of progress began several days before the first little green steroid pill touched my lips.

Second, I have had a fair amount of experience with steroids during efforts to control my autoimmune hemolytic anemia (AIHA). Four mg of dex is a pretty minimal dose (equivalent to about 21 mg of methylprednisolone.) It’s nothing to sneeze at, but 4 mg, in the past, has done little in and of itself to reduce my nodes.

Now, since I’ve started taking it, the progress on my nodes has continued (albeit at a slower pace than the post-Arzerra burst). It’s possible that it is a coincidence, but it’s also possible that the dex is a contributing factor, working in synergy with the Arzerra (anti-CD20 monoclonal/steroid combinations are well-known in CLL treatment.)  Once I’m off of it -– hopefully, sometime in the next week to ten days  my body will be adapted to 10 mg of Revlimid daily without causing a rash -– I’ll be able to judge whether it has had any effect. Obviously, if the nodes come back a little, that might indicate that it has.

But the bottom line is that the underlying progress is a result of the OL (ofatumumab-lenalidomide) protocol. Why or how it suddenly decided to visibly work after three months is a Farnsworthian mystery. My advice to those starting Revlimd and Arzerra is to hold on, get ready for the long haul, and be aware that you may not see immediate results like you do with most treatments. That makes it a little counterintuitive and a little hard to take at times, but you might just be surprised one day. I certainly am.