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.”

* * *

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.

Rash decisions, and other Revlimid news

My latest CBC is suitable for framing: Lymphocyte count “normal.” Red count “normal.” Platelets “normal.”

But all is not picture perfect, as swollen lymph nodes remind me every time I pass a mirror. There have been some developments on that front, which I’ll get to in a moment.

But first, speaking of red, I have run into a rash roadblock. Taking Revlimid (lenalidomide) is not unlike playing a video game with your health. Once one problem is solved, another is presented. The goal is to successfully navigate your way through each challenge and get to where you want to go, which in this case is a meaningful remission.

I had finally managed to get myself up to taking 10 mg every day again without inciting major tumor flare or becoming a complete zombie. And then, last week, about four or five days in, a rash started to develop. Each day it grew worse until it was apparent that Something Had to Be Done.

The rash didn’t itch and it wasn’t painful. Imagine a series of small, pastel-red spots, which started on the feet and ankles and then began to appear everywhere. Fortunately, I was scheduled for a doctor visit and Arzerra (ofatumumab) infusion last Thursday. By Wednesday night, my face was starting to turn red.

As Dr. Belle said when she saw me, “I feel sick just looking at you.” So she suggested that we stop Revlimid for three or four days, long enough to let the rash clear. Keeping the body in a state of so much inflammation is not good, she said. The last thing we want to do is trigger some sort of zany, inappropriate response from the CLL clones. 

So here I am on the last day of no Revlimid, the rash gone except for the stubborn feet and ankles. The plan is to resume Revlimid at 10 mg every other day and manage any new rash with dexamethasone and antihistamines. (The Benadryl I had on Wednesday and Thursday made only a mild dent in the rash, thus the steroid. I also had a 125 mg hydrocortisone shot on Thursday, which was part of my Arzerra premeds.)

If I can tolerate 10 mg every other day, we’ll add 5 mg on the “off” day and work back up to 10 mg every day. Since I was rashless when I was doing 5-10-5-10 before, I suspect that I won’t have much of a problem again until I get to 10 every day. We shall see, hopefully not red.

* * *

Meanwhile, I began to notice some subtle progress on the lymph nodes when I was back up to 10 mg daily. Dr. Belle says my spleen is reduced and that some of my neck nodes are spongier. I have lost about eight pounds in the past two months or so, and the weight loss seems to be accelerating. Is it water weight? Spleen and lymph node weight?  It’s not from exercise, which Revlimid fatigue tends to prevent, and I’m not on a diet.

And being off Revlimid while having Arzerra has also been interesting. For the first time I am noticing some neck slimming following an Arzerra infusion. Could this mean that the Arzerra is working better without the Revlimid added to it? Could the Revlimid  have been contributing to some subtle tumor flare that was masking the effectiveness of the Arzerra all along? Or could the higher doses of Revlimid that I had been taking have set the stage for the Arzerra to work more effectively than in the past?  After all, the Revlimid doesn’t disappear from your system immediately when you stop taking the pill. I suppose this will sort itself out as the game goes on. Let’s just say that for the first time I am cautiously optimistic that this protocol may be doing something about my disease bulk.  

* * *

The last thing I’ve noticed during my mini-vacation from Revlimid is how much more clear-headed I am starting to become. It’s easier to get things done, and not just because my

energy level is higher. I am losing that Revlimid-induced quality that can best be described as  “dullness.” It’s not so much fatigue as it is feeling listless and not on top of things, like there’s a layer of invisible cotton between me and the world. I have to admit that this feeling is hard to take over the long haul. It’s easier to cope with tumor flare or a rash. Hopefully, when I’m back to 10 mg daily and rash-free, it will gradually disappear. Otherwise it’s going to be a long nine months, which is how long I have left to go on this protocol. Of course, if I do get to that meaningful remission at the end of the game, it will have been worth it.

Life in the slow lane

It’s been about nine weeks since I started lenalidomide, aka Revlimid. With nearly ten months to go in the protocol, it’s still hard to point to any significant progress.

As you may recall, the initial dose of 10 mg daily led to severe tumor flare and was cut back to 5 mg within the first week. This lower dose was accompanied by a reduction of drug-induced fatigue, as well as a reversal of the tumor flare.

After about a month, my oncologist decided it was time to work our way back up to ten again. For a few weeks I did 10 mg every third day –- 5 mg, 5 mg, 10 mg, 5 mg, 5 mg, 10 mg -– and so on. That proved tolerable, so I am now on 10 mg every other day.

This has been accompanied by the return of noticeable fatigue on the day following the 10 mg dose. Yesterday I was about as zonked as I get. It’s not a sick or fluish feeling, more like a  spaced-out, moving-through-Jello, can’t-deal-with-anything-complicated kind of thing. I got a full night’s sleep –- that’s one thing you can count on with Revlimid –- but also required two naps during the day. Prior to Revlimid, I always used to wake up refreshed from a nap. Now I usually wake up almost as tired as I did before I started.

My reaction of late to 10 mg has not always been so severe; perhaps the drug is beginning to build up in my body. So it will be interesting to see how my tolerance to it develops. The plan is, of course, to go back to 10 mg daily as soon as I can stand it.

Besides the Revlimid I am getting monthly infusions of ofatumumab, aka Arzerra. I haven’t had any infusion reactions, nor any dramatic results.

My CBCs do show progress. Absolute lymphocyte count has dropped from around 12k to a just-above-normal 5k. Platelets are holding steady at low normal, neutrophils remain strong, and the hemoglobin, hematocrit, and overall red count have improved and now sit at low normal as well. I’m pretty sure my autoimmune hemolytic anemia will stay in its box as long as I’m on this protocol.

But the real battle is in the lymph nodes, where most of my disease resides, and where it's hard to know what's happening, other than "not much so far." During my 5 mg month the nodes seemed to be getting just a tad better -– a little softer and spongier in the neck, for example. I've lost a few pounds, so my abdomen looks a little less distended, but it's a leap of faith to say that I lost abdominal lymph node weight.

I think it's accurate to say that the nodes show no truly measurable improvement since I started all this nine weeks ago. How much is drug resistance, how much is the propensity of Revlimid to cause even mild tumor flare, it’s hard to say. The other factor is that it could be too early for noticeable improvement; many patients report that it takes several months to see progress, and one study showed that it took patients a median time of about six months to show best results. The sooner I can get back to 10 mg daily, the sooner things may start looking better.

So a lot of this is a waiting game, accompanied by intermittent bouts of fatigue. For those of us used to seeing rather immediate results from traditional chemo, it’s also a lesson in patience.

The only thing I can safely conclude so far is that the protocol has brought me stable disease. The nodes are not really improving but they’re not getting worse. The AIHA is under control. My red counts have improved, though this potential added energy is offset by Revlimid fatigue. Only time will tell whether I get from stable disease to partial remission.

Take two aspirin and call Obama in the morning

My recent post celebrating the passage of health insurance reform led to an interesting debate in the comments section. There are sincere people on both sides who put forth arguments of merit. At the risk of causing more headaches for myself and others, I want to address some of the points made.

First, this new law is about as conservative as a liberal reform can be. There is no public option. The bill was supported by Big Pharma, with which the White House cut a deal early on. While these factors may be mightily annoying to some people on the left, they also mean that the worst fears of those on the right are unlikely to be realized. Decisions about what care you can have will still be made by corporate bureaucrats –- as opposed to government bureaucrats –- although the reforms do provide some better consumer protections, such as changes to the appeals process. Drug companies will still be able to charge American customers an arm and a leg and a spleen, which means they will still have money and incentive to develop new therapies for CLL and other diseases. There will be no government-mandated NICE program, like they have in the U.K.

The concerned physician wrote in his comment that "Healthcare providers will either grow wealthier, or they will leave the system, further diminishing availability of care." I am guessing that with a new group of 32 million captive customers, health insurance companies won't suffer. They have enough money to hire attorneys to exploit loopholes or gray areas in the law, which has already begun, as the recent flap over whether they can weasel out of covering children with preexisting conditions demonstrates. There are lots of ways for health insurers to game the new system, just as they have gamed the old.

On another point I made, the doctor wrote: "I hope that you really don't believe that many people died for lack of coverage. As a physician I categorically assure you that that has not been the case."

Alas, there is plenty of evidence that more than a few people have suffered fatal consequences from lack of insurance. Last fall, researchers reported in the American Journal of Public Health that an estimated 45,000 deaths per year in the United States are associated with the lack of health insurance. A 2007 study from The American Cancer Society found that uninsured cancer patients are 1.6 times more likely to die within five years of their diagnosis than those with private insurance.

The bottom line, as I see it, is that the current system is unfair (take refusal to cover preexisting conditions as an example) and unworkable for too many people (the estimated 45 million Americans who have no insurance, those even with insurance who face bankruptcy if they become seriously ill, those with chronic diseases -- hint, hint -- who face dollar caps on coverage, those whose insurance can be lost at any minute due to the capricious whims of an insurance company).

This reform package is flawed and will no doubt need some corrections as time goes on. There may well have been better ways to go about it. But in correcting some of the worst abuses, it is a step in the right direction. We may have gone from bad to middling, but as we CLLers know from our treatment experience, a partial response is better than none at all.

Post Secret CLLer?

I found this image on Post Secret, the blog run by Frank Warren, a guy in Maryland who encourages people to send in anonymous post cards. These cards usually express things that the senders would otherwise keep to themselves.

No, I didn't send it in, and I can't be sure it's from a patient with chronic lymphocytic leukemia. But it does speak for all of us, I imagine, although I don't feel guilty for not suffering more.

The fog lifts

The fatigue that accompanied the start if my lenalidomide (Revlimid) therapy has pretty much disappeared after about three weeks. I didn't realize how bad it was until I started to come out of it and suddenly found myself with a lot more energy than I expected to have. I had started to forget what "normal" felt like. 

After therapy began on March 4, I began sleeping nine to ten hours a night and napping for perhaps an hour during the day. Even during my waking moments I was running (or I should say moseying) at about half speed. As this routine dragged on it became rather depressing. I have been fortunate in that I have not had the CLL-related fatigue that some patients report. Living with a drug-induced taste of it for a few weeks opened my eyes to how difficult it can be. 

Is the cessation of fatigue dose-dependent? I started at 10 mg daily, which was reduced to 5 mg about a week in. The fatigue still continued for awhile, though. I will no doubt attempt to step up to 10 mg again at some point in the near future. I'll just have to see if the fatigue returns.

Other than that, there is little to report so far. Blood work shows that my red counts continue to improve. There's no sign of low platelets or low neutrophils, either or both of which can accompany Revlimid therapy. It is possible that there is a slight, incremental improvement in my lymph nodes, but these can wax and wane under normal circumstances so I hesitate to read too much into it. One study put the median time to best response at 5.9 months and I haven't even been on lenalidomide for a month yet. Patience is both an art and a discipline.

Finally

Today, with President Obama's signature, health care reform became the law of the land. It’s not perfect but it’s a significant improvement over the mess we have now. The United States has taken a big step toward joining the industrialized world when it comes to insuring that the basic needs of its citizens are met.

It is a shame that thousands of Americans had to die on the way to this day because they couldn't afford insurance or because their insurance provider found a reason to drop them when they got sick or refused to cover preexisting conditions.

Despite their crocodile tears, Republicans did nothing when they controlled Congress and the White House to address those issues, not even basic matters of fairness that most reasonable people would agree upon. Now they have gone off the deep end, embracing all manner of wingnuttery.   

A new Harris Poll of Republicans shows that 67% believe that President Obama is a socialist, 57% believe he is a Muslim, 45% agree with the Birthers that Obama was "not born in the United States and so is not eligible to be president," 38% say the president is "doing many of the things that Hitler did," and 24% believe that Obama "may be the Antichrist."

And these people think they know better when it comes to health care?

Republican pols, of course, are running around like headless chickens pandering to the rightest of the right wing, squawking "repeal" and saying that Americans are against health care reform. Today's USA Today/Gallup Poll shows Americans supporting the measure by 49% to 40%. As Taegan Goddard of Political Wire pointed out on Monday, analyzing a CNN poll: “Parsing the numbers shows that many of those against the plan actually oppose it because 'it is not liberal enough.' In fact, 52% of Americans either support the current legislation or think it should be more liberal, while only 43% oppose the plan saying it is 'too liberal.' "

At some point in the future, people will look back and wonder what all the fuss was about. And more people will be alive to wonder, thanks to this legislation.

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.

Uneventful ofatumumab

The start of treatment was delayed two weeks because of a cold. Colds, as some of you know, can be a particular challenge to CLLers since we have degraded immune systems with few functional B lymphocytes, lowered immunoglobulins, and too many CLL clones gumming up the finely-tuned works. 

Sure enough, my lymph nodes grew as the clones reproduced in a frenzy, trying vainly to fulfill their intended function. Somehow I managed to get over the worst of the cold in a couple of days, after which it dragged on at a low level, but not quite low enough to safely begin treatment. 

Once I had recovered, things got underway last Wednesday with the opening dose of ofatumumab, aka Arzerra. GlaxoSmithKline starts you out with a baby dose of the stuff, 300 mg over six hours, just to make sure you don't have any serious reactions. The infusion rate begins at 12 mg an hour and is gradually increased every half hour to 200 mg. Premeds consisted of two Tylenol, 50 mg of IV Benadryl, and 100 mg of IV hydrocortisone, aka Solu-Cortef. 

Absolutely nothing happened, other than the Benadryl putting me into a rather comatose state. Being a fully-humanized monoclonal antibody, ofatumumab may cause less of an allergic reaction than its cousin, the mouse juice rituximab. I have often had mild infusion reactions to the latter -- flushed face, tightening of the throat, and the like -- usually during the first infusion of a cycle. With the ofatumumab they may as well have been giving me water. That doesn't mean no one ever gets a reaction; it can and does happen, it just didn't happen to me.

The one thing I did notice is some mild redness on my neck (below the ears) where the lymph nodes are inflamed. Back when Rituxan was working pretty well on me, I used to get the same thing. This seems to me to be more a consequence of the drug working than an infusion reaction, especially since I have only noticed it toward the end of an infusion or after it is done. Other than that, I can't report any noticeable effects of the Arzerra, but at 300 mg, I wouldn't expect to see much progress.

Next week I'll be given the customary 1000 mg dose, along with more of the dreaded Benadryl. The day after I start the lenalidomide (Revlimid), 10 mg daily. In other words, Houston, we will have lift off. 

My little OL protocol: ofatumumab and lenalidomide

Yes, that little ol' lab rat, me, is about to undertake a cutting-edge protocol to fight chronic lymphocytic leukemia: ofatumumab and lenalidomide.

I call it the OL protocol, and there’s a trial at MD Anderson in Houston that’s just starting to accrue patients for a two-year study of this new drug combination.

Thanks to a forward-thinking oncologist who is willing to fight like hell for her patients, and thanks to two drug companies that are willing to help those who can’t afford to pay the enormous costs of the treatment, I am going to be following that protocol from the comfort of home, or at least from a comfortable chair two hours away.  I start next week.

Because I will be one of the first CLLers to try what could become an important  therapy for our community, I will blog about my experience on a somewhat regular basis.

To briefly review, ofatumumab is the fully-humanized anti-CD20 monoclonal antibody that was approved for CLL in October by the FDA. It goes by the trade name Arzerra but old CLL hands (Man, I guess I am one of those!) may better know it as HuMax-CD20. It was developed by Genmab and licensed to GlaxoSmithKline.

Lenalidomide, which I wrote about in my last post, goes by the name Revlimid, and was developed by Celgene. It has been approved by the FDA for Myelodysplastic Syndrome and Multiple Myeloma and has had some interesting results in CLL.

December’s American Society of Hematology meeting included a report from MD Anderson on a trial of rituximab and lenalidomide in 37 relapsed and refractory patients, all of whom had used Rituxan in the past. The new OL trial appears to be based, in terms of timing and dosages, on their experience with RL.

Dr. Alessandra Ferrajoli and the team o' Texans reported an overall response rate of 68%, of which 51% received a Partial Remission and 16% a Nodular Partial Remission. Sixteen percent had stable disease and 16% failed the protocol.

Other studies have shown an overall response rate of 32%-47% among relapsed CLLers given single-agent lenalidomide, so MDA considered the combination with the monoclonal antibody to be “superior to single agent lenalidomide, despite all our patients having received prior rituximab.

“Additionally," the authors wrote, "there was no increase in toxicity and lenalidomide-associated tumor flare reaction was less frequent and less severe with this combination compared to single agent lenalidomide.”

For the record, a 2008 MDA study of single-agent lenalidomide in relapsed patients showed an Overall Response of 32%, which includes a Complete Response of 7%. An additional 25% achieved stable disease. A 2006 study by Dr. Asher Chanan-Khan’s group at the Roswell Park Cancer Institute in New York reported an Overall Response rate of 47%, with 9% achieving a CR. Another 18% had stable disease. 

My prospects

Clearly, my response can fall anywhere on that rather large map, landing from CR to CRap. And just as clearly, this protocol is not going to be a cure for CLL nor an avenue to a molecular remission. But it may serve as a welcome and effective control, and I have reason to be optimistic as I begin.

I have always responded well to whatever new drugs I have been given and there is no change in my FISH profile that would indicate a loss of that ability. Of course, having had several treatments over the years, some disease resistance has developed in response. Indeed, the CLL cells have created a rather secure suburban community in my abdominal lymph nodes. The ability of lenalidomide to disrupt that micro-environment, including the nurse-like cells that help CLL remain comfortable, is a definite plus.

I am also younger and in better shape, both in terms of my health and disease state, than many of the participants in these trials. I can weather the side effects -- notably fatigue, tumor flare, and possibly low neutrophils and low platelets -- that may come my way.

Ofatumumab will assuredly be more effective on me than rituximab, to which I no longer respond well after many, many uses. Indeed, ofatumumab has given a new lease on life to any number of people who have tried it before me, some of whom I have known personally, and many of whom had stopped responding to Rituxan.

Readers may recall in my last post that I said I did not wish to use ofatumumab as a single agent, that it was too important a weapon to use gratuitously. That remains the case, and I don’t see the OL protocol as a wasteful extravagance.

I have a lot of abdominal lymph node bulk, enough that a year’s worth of steroids, Rituxan, and even cyclophosphamide were unable to make much of a dent in it. Ofatumumab is a new drug for me; with some luck, my nodes might respond the way they did to Rituxan when I first used it six years ago. In other words, they may undergo a noticeable reduction that can then be hammered home by the lenalidomide.

Can I completely clear the abdominal nodes? It would be quite a feat, but all things are possible in life and combination immunotherapy. Even if I can’t, can I reduce the bulk by a meaningful amount -- say 50% -- and throw my disease level back to where it was in 2005 or 2006? I think even hardened realists would say that is possible. The 2008 MDA study of single-agent lenalidomide reported a greater than 50% improvement in lymphadenopathy in 41% of patients. I'm probably starting from a worse position than most patients in that trial, but remember that we are also adding the ofatumumab.

Such a reduction in disease –- along with hopefully enhanced immunity, including a cessation of autoimmune hemolytic anemia, with its endless threat of hemolysis –- makes this an especially intriguing protocol.

Nothing else out there holds the prospect of doing all these things for me, especially with minimal toxicity, and these are all things that need to get done. For what it’s worth, some of the experts find this drug combination to be full of potential. I am told, for example, that MDA's Dr. Michael Keating is “very keen” on it. 

Perspective: Playing for time vs. transplant

It’s the right thing at the right time, as far as I’m concerned, which brings up an interesting point. When I was diagnosed in 2003, neither of these agents existed for CLL. Despite the feeling among us patients that progress can never come fast enough, here is a case where two new drugs may make a significant impact on my disease. So there is indeed some wisdom in playing for time if you have the stomach for it.

Playing for time is something that you have to finesse as you go, since the disease is not static. Much depends upon your biological markers -- IgVH mutational status, chromosomal deletions per FISH, ZAP-70, and CD38. But the bottom line, which I think is sometimes given short shrift in patient discussions, is your actual disease progression, clinical history, and ability to respond to treatment. 

To my mind, it's the practical stuff that counts. Which brings us to the stem cell or cord blood transplant, sometimes seen as the CLL end game. For many of us, and maybe even yet for me, that will be the case. But I think it is a little premature to be swept along on some kind of bandwagon, thinking that transplant is inevitable and maybe even desirable. Perhaps, if meaningful control of CLL can be obtained by means of OL and other agents in the pipeline, some of us will have a realistic alternative.

Frankly, transplant results are virtually impossible to predict. Talk about arbitrary and capricious: You can die. You can be cured, or at least disease free for a long, long time. You can also relapse and have to wake up to fight the whole messy, draining battle all over again. You can struggle along for years with debilitating graft vs. host conditions, from skin reactions to gastrointestinal problems to seizures.  Many patients are grateful to be alive despite the side effects; others have regrets. 

One wrote to me off the blog: "Do not underestimate the effects of chronic GVHD. When you read about them, they might not sound too bad; however, the collective experience of multiple GVHD effects can make life after a transplant quite miserable.  And chronic, in this sense, must be seen as a permanent condition."

I will never forget Dr. Terry Hamblin's comment that he knew of two patients who were so beset by post-transplant graft v. host problems that they killed themselves.

There is a yin and yang to this, of course, and I am not discounting the success stories, those who write that they are "recovering nicely" after two years, and those who are a few years in with only minor problems, nothing to get too excited about, and with no regrets about having taken the big step. 

I keep a list of blogs on the right side of this page. Scroll down and click on those of the transplant patients: Brian Koffman, Jackie Sue, Ron Gottula, Dan O’Mara, and Harvey's Journal. Take a look at Tom McCune’s website; Tom was once the CLL cure “poster child,” now in relapse. Check the posts at CLL Forum and ACOR from patients like Chonette and JursyGurl, both of whom are having success with minimal trouble so far (you go, girls!). Read Raywood's Great Stem Cell Transplant Caper, and then read all the nice comments about him on CLL Forum's "In Loving Memory" page; Ray was a character, an irrepressible optimist and guitar picker who put CLL to Country music. But all the sunshine in the world doesn't guarantee success. Neither, for that matter, does a Vulcan-like level of meticulous preparation.

Gather all this –- and more -– into your head and you may conclude, as I have, that the transplant is unpredictable at best, freakishly difficult much of the time, and, obviously, fatal at worst. You may as well go into the hospital singing "Luck Be a Lady."

"They call you lady luck
But there is room for doubt
At times you have a very un-ladylike way
Of running out . . ."

I think the outcome is well out of your hands despite however many statistics you arrange in your favor (the optimistic configuration of published data can indicate an element of wishful thinking that creeps into even the most rational of minds.) When the chips are down, you're putting all your chips on the table. A transplant, to my mind, is something you do when you HAVE to do it and no sooner.

It is not a battle that I am afraid of, but it is not one I am jumping to fight if there is a wiser way to conduct the war. 

I am hoping that OL will be an effective weapon, something of a game-changer, at least for a reasonably long time. I’m 53, healthy other than the CLL -– my blood pressure tests out these days at around 120 over 70 and my primary care doctor wants to frame my lipid profile.  My quality of life is good (when I’m not hemolysing).

Beyond the medical facts, CLL has taught me that I am mortal, and so it has ironically given me the gift of being able to live life fully today, to let go of old regrets and unhealthy patterns, and I am happier than I have ever been.

So why not still play for time? 

There is a fine line in CLL between being too proactive and too reactive. Much of my CLL journey has been spent trying to find and stay close to that line. At times I have been more successful than others. I think -- I hope -- that I have found it with the OL protocol.

It's the line of scrimmage between me and the disease. It’s first-and-ten and I will move the ball down the field as best as I am able, however many yards at a time. I’ll report on it as I go.