A real pain in the neck

And I mean that literally. Yes, that's me, laying in the ER, just after a drain was put into my neck.

It all began with a lymph node under my left jaw that swelled up, and kept swelling and swelling, and swelling and swelling, until I could barely open my mouth. I've heard of CLL patients getting massive nodes before, but this was no ordinary CLL event. 

It turns out that a bit of bacteria, something in the strep family, got caught up in the node and caused an abscess. The CT scan at the ER pegged the node at 5.0 x 4.1 x 3.3 cm. But the way it was stretched over my neck, it felt much larger than that, and measured by touch more like five inches than 5 cm. It was crushing my neck muscles and salivary glands. Had it gone on for much longer it would have dislocated my jaw.

According to the ENT doc, such abscesses are not uncommon among the general population. (Who knew?) At first there was some concern that the abscess could have originated from a necrotic place within the lymph node, but cultures of the chocolate-brown pus showed a garden-variety strep. (The culture report states. "Mixed flora (multiple species present). Predominately Beta Hemolytic Streptococci, Group F.") Fortunately, blood cultures showed no bacteria in the blood, which would have meant sepsis, a much more serious condition and one that would have kept me in the hospital beyond the three days that I was there.

Mmm. Chocolatey brown pus in syringe at left.

I was admitted so that I could receive IV antibiotics, clindamycin, which I am now taking orally at home. The drain is still in my neck and will be there for at least another week.

I haven't been a patient in a hospital since 1964, so the whole routine took some getting used to. Who knew you could order meals at whim off a room service menu these days? Or that the nurse would strap air bags to your legs that puff up and down to prevent deep vein thrombosis? I caught up on my television viewing, even if I didn't get a whole lot of sleep.

I do believe there is a CLL-related cause to all this. Prior to the abscess, I was on Revlimid at 5 mg, for four days in a row. The tumor flare reaction was so incredibly way-over-the-top that my guess is the bacteria made its way into the node as part of that process. The tumor flare was so bad that I had to stop the Revlimid and go on steroids to bring it down.  It was the failure of the one node to go down very much -- and then its ballooning overnight once I went off steroids -- that alerted me to the fact that something unusual was happening.

Now 5 mg of Revlimid over four days is a baby dose, as these things go, and I have been on and off the drug for a year and a half without the monstrous flare I encountered this time. So why the sudden overreaction in terms of tumor flare? 

I can't say. What I can say is that a recent paper shows that tumor flare predicts response to Revlimid in CLL. That's a good thing in my case. But tumor flare like this???

There are a number of things going on that I'll go into later, but suffice to say that I may not be able to tolerate Revlimid to the degree needed to keep using it. I've been off of it since the flare, and until the abscess is gone and the lymph node heals, I can't do anything in terms of treatment that might put stress on the node.

In the meantime I lurk around the house like Frankenstein with one knob. Fortunately I work at home, where I can't scare small children.

This is how the tumor flare in my neck looked after four days of Revlimid, and the photo barely does justice to it; below is my neck in its more normal state some ten days later.

Hang on

Here comes September 3 again, the anniversary of my diagnosis with chronic lymphocytic leukemia. It approaches each year like the garbage truck that groans down the street every Monday morning, screeching, growling, and filling the neighborhood with diesel fumes.

In other words, it’s unpleasant. But it’s made palatable by the fact that I am still here to reflect upon it.

This is my eighth anniversary, and I have the song “Hang on, Sloopy” running through my head. It’s easy to figure out why. If I have any advice to offer as a grizzled veteran of CLL, it’s “Hang on.”

* * *

On some fundamental level I have never accepted that CLL will kill me. It’s a silly disease, all these B cell clones making copies (cue the Richmeister from Saturday Night Live) and clogging up the works. The clones can be killed rather easily, it’s just that it’s nearly impossible to kill every last one. And you can have very good quality of life while living with CLL. Cancer is never good, but on the Bell Curve from Hell, CLL is at the better end.

Call me crazy –- and some of you no doubt will -– but my refusal to accept that CLL is my end is just the sort of wild-eyed faith that cancer patients who beat cancer sometimes have.

So I have spent eight years muddling through, often rejecting the advice of doctors, which is usually conflicting, about what to do.

The choices, until lately, haven’t been very good. One doctor told me to do PCR and “get on with my life.” He was reduced to mumbling when asked what I should do after PCR wore off in two or three years. Another doctor did the obligatory push for fludarabine; after he became assured that I was an adult and not prone to panic, he admitted that well, no, it really isn’t as effective over the long term as it needs to be. I've looked seriously into transplants, which have been advocated by some very reasonable people, and have come away thinking they're too risky on too many levels. (I'd still do one if I had to -- I'd do anything if I had to, except vincristine again -- but I have a very high bar when it comes to defining "have to.") What I'm saying is, scratch the surface of any responsible medical professional and they'll admit that most treatments currently in use have unfortunate limitations.

It can be easy to get swept up in the world of incremental progress that researchers make. But the bottom line is that improvements do not mean that the progress is satisfactory.

So I have waited until I have been forced to act, I have avoided the most potentially damaging options whenever possible, and I have waited some more.

Is this a wise approach? I don't know. It's what works for me. In the absence of a way to win the war, I find it better to sit and wait for the enemy, conducting a guerrilla campaign around the edges, than to go all in and claim a Pyrrhic victory.

* * *

This has come at a cost. No matter how you choose to fight CLL (or choose not to fight it) there are risks. It’s very much a war of attrition, as Terry Hamblin once put it.

This blog is filled with posts about the challenges I have faced. For those of us not “blessed” with indolent CLL, the disease can only get worse over time. Treatment helps, but it also exacerbates the situation by increasing disease resistance. This goes for softer treatments as well as harder ones. Failing to treat when you ought to -– sometimes we need to be proactive -– leads to similar consequences, since the disease will grow and potentially evolve into a worse form just for the hell of it.

In hindsight we can see how things might have been different had we done X, Y, or Z. But in the heat of battle, it is, as they used to say in the military, S.N.A.F.U. You just do your best and hope nothing explodes.

And if you don't choose too badly, if you respond decently to treatment, if your body proves more resilient than not, if a little luck comes your way, you can muddle through.

* * *

After eight years, I see tangible evidence that waiting pays off.

We’re all familiar with the great news from the University of Pennsylvania. Finally, a T cell therapy has been developed that can apparently wipe out the disease, even in cases considered to be hopeless. It’s like having a successful transplant without all the risk. This means the cure, or de facto cure, could be at our doorstep. 

I have seen other drugs become available, either officially, or off-label, or in trial. There’s Revlimid, which for some people is a control. CAL-101 and other kinase inhibitors, which are doing well in studies. (I wonder how Revlimid and CAL-101 would work together?) Ofatumumab has been added to the list of options; it’s no panacea, but it helps.

I have also seen some flavors of the month fall by the wayside, notably alemtuzumab. And I have seen opinions change: The 11q deletion, once thought to be the kiss of death, isn’t always so. The point is that the longer we have to learn, the more we know.

So my thought this anniversary is to hang on. The longer you can drag things out, the greater chance that scientific progress will come up with something to save your sorry ass. It doesn’t matter how inelegantly you arrive across the finish line, just so long as you get there.

Eight years later, I’m still at Stage 2. My hemoglobin and platelets have weathered the storm. I’m no more prone to infections than I was when diagnosed. My quality of life is pretty much the same, challenged occasionally by side effects from the Revlimid I'm taking. The disease is definitely bigger and harder to treat, more node-based and less leukemic, but Revlimid is holding the line. (I got lucky with that one; luck is part of the equation, remember.)

I’m basically none the worse for wear. And crazy, of course, as a sack full of otters.

Benediction

When my brother Rick was in Vietnam, a grenade went off nearby. It knocked him out. There was shrapnel in his skull.

He could see himself floating above his body. He saw loved ones around him and felt a profound sense of peace. It was, he said, the most wonderful thing he’d ever felt. (This was the mid-1960s, before reports of near-death experiences were publicized in books and the media.) It was, Rick said, the last thing he expected to happen.

And then he was awake. A paramedic had saved his life.

“Why did you do that?” my brother asked, after which he slugged the medic as hard as he could.

* * *

Rick died Friday of the stroke that felled him two months before. He was not a religious man, but the near death experience stayed with him and made him unafraid of death. Years later, after a motorcycle accident, he had the same experience, saw the same things, until he was snapped back to life.

Being unafraid of death does not always make it easy to say goodbye, of course. Fortunately, there was enough time after the stroke for the process to work its way through, and for moments to be shared. Heavy, meaningful things were said, but mostly it was just the joy of companionship. We looked at old photos and talked about old times, which became more difficult as he lost his ability to speak clearly. And he wanted to know what Marilyn and I were up to, no matter how unimportant our activities seemed to us.

We were not present for the final days of his decline. His wife, Mary, said he had begun to see his twin. Rick's twin brother was stillborn and now, somehow, Rick saw him there in the living room. What he looked like, what he communicated to Rick, I do not know. How much of the transition to death is illusion, how much is reality, I also do not know, except to say that it is a mystery that befuddles the living.

* * *

Rick confided in his wife the most, of course. At one point he told her that he had wanted to be there for me when I died, and he was sorry that, instead, I had to be there for him.

I came to realize that, somewhere in the back of my mind, having CLL had created the expectation that I would die before everyone else in my family. Not just before those who are younger, which would be expected anyway, but also before Rick, who was 11 years my senior, and even before my father and stepmother, who are now in their 70s.

Not only was this my expectation; it was obviously Rick’s as well, and perhaps is shared by other people I am close to. It’s not something they talk about, just something they assume.

This assumption conflicts with another expectation that I have, which is that I will manage to muddle through thanks to new drugs like Revlimid, and perhaps have a reasonably normal lifespan after all.

Time, which I am aware is ever-short, even for the healthy, will tell.

And if Rick’s near death experiences are right, he’ll be there for me when I die, after all -- just not on this side of the curtain.

Off and on

As a newbie, CLL was the center of my universe. As time has gone on, it has become more like the chronic condition that it is -– albeit a chronic condition with a potentially deadly bite. My focus, by both choice and necessity, has gone elsewhere. I have a business to run, a family to attend to.

Other questions, big and small, tend to take over my day. What is a tambour door? Should I put the old treadmill on Craigslist or Freecycle? Why do the doves always build their nest in the windiest corner of the front porch, from which their nest will be blown away?

Of late, my time and energy has gone toward a more serious and sad situation. My older half-brother, who lives about three hours away, has had a severe, debilitating ischemic stroke. He’s been in the hospital for several weeks. At first it wasn’t clear that he would survive. But he has emerged with his faculties intact, as well as some movement on his right side. At best, he faces the prospect of a long and difficult recovery.

He’s 66, eleven years older than I am, and his current condition has shaken the frame of reference I formed as a child. He was always taller, stronger (he was in the Marines), and more world-wise. Now, in dealing with family issues and the health care system -– all the details, from the mundane to the deeply emotional, things that CLL has prepared me for -– our roles are reversed.  

This is not his first stroke, and our mother died at 57 of a pulmonary embolism and had a history of phlebitis. I don’t respond to the blood thinner warfarin (Coumadin) at 2 mg and 4 mg doses. Apparently clotting issues run in the family. 

Which brings us back to Revlimid (lenalidomide), a potential side effect of which is the creation of blood clots. Readers will recall that I have had two TIAs, or transient ischemic attacks (mini-strokes) while on the drug.

*  *  *

I am acutely aware that I have been allowed the time to deal with all things great and small courtesy of Revlimid. For a year, it stepped in to halt the progress of a fast-moving disease when nothing else would reliably work.

Starting March 15 of this year, I went off Revlimid for three months. One reason was to give my body a rest, in part because clotting issues had arisen. Another was to see how long my remission held without it. And a third was related to my application for a clinical trial involving CAL-101, the node-busting drug that has created a great deal of hope among CLLers with bulky disease, which pretty much describes me.

I may yet get into the trial, if the trial arm is ever organized. It has been “two more weeks” for months now, and even the principal investigator has stopped trying to predict when the drug companies involved will sign off on everything. When the arm is finally organized, I’ll need to be off Revlimid for 28 days before the initial round of testing and evaluation to determine my eligibility.

Meanwhile, I learned during these three months that I probably shouldn’t be off Revlimid for more than about six weeks. The first month was quite encouraging: The nodes continued to get smaller and smaller and I lost weight. The second month involved a brief plateau. During the third the nodes began to come back, steadily and surely.

A month into my “vacation,” which was also a vacation from blood thinners, I had a PT/INR test done. My clotting time came out at baseline, 1.0, which is exactly where it had been when I had been on warfarin. My oncologist has now ordered an extensive clotting panel -– Nurse Dracula took 14 vials of blood -– to determine if there is anything unusual going on. This will help us determine what the best blood-thinning strategy is.

In the meantime, I have started a minimal dose of Revlimid, 5 mg every other day, accompanied by aspirin. After a few doses I’m noticing a fair degree of tumor flare, not as bad as it was when I first began the drug, but definitely pronounced. This will probably last for two to three weeks.

* * *

During all this time my blood tests showed some interesting things.

As expected, my absolute lymphocyte count rose, from 8.6 just before I stopped to 19 two months later, then dropping back to 10.5 just before I resumed. This fallback was probably due to the CLL cells returning to the nodes.

My platelets, which had been increasing before I stopped, quickly fell back to around 130, which is what “normal” has been for me for several years.

My red count remained strong. Hemoglobin was 14.5 just before I quit, 15.1 just before I resumed. This tells me that after three months off the drug, there was no sign of the dreaded autoimmune hemolytic anemia (AIHA), which had plagued me before Revlimid.

So let me repeat here once again what I’ve said in this blog before: I am one anecdotal case but I am pretty solid evidence that Revlimid can have a huge impact on AIHA, even bad cases of it. If you are dealing with this scourge and have begun to run low on traditional options, consider Revlimid!

Finally, there is some bad news in the mix. My B2M had been as high as the 11s while I was on Revlimid. I attributed this to a great deal of ongoing cell-kill as my drug-reinforced immune system did battle with the evil clones. My vacation appears to have substantiated this as the B2M has fallen to a consistent 7.

The bad news is that my baseline B2M is that high. It’s way over the top. In a normal person it should be less than 2.3. In a CLLer it should really be less than 4. So what this tells me is that my disease is still big and aggressive.

And what this means is that Revlimid -– which hopefully will continue to work as it did before -– is going to be a constant and necessary presence in my life, stroke risk and all.

Unless, of course, things work out with CAL-101.

* * *

It's an odd existence. CLL reminds me of handling a rattlesnake. There are people who deal with venemous snakes every day, usually harvesting the venom to use as an antidote to snake bite. These people live with constant danger, and with luck they'll never be bitten. But there's a thin line between living a normal daily existence and something going terribly wrong. My childhood doctor collected snakes as a hobby, and one day his office was closed and he wasn't there anymore.

When I was in first grade we lived in Poston, Arizona, near the Colorado River. It was teeming with wildlife -- mallards, skunks, bobcats, scorpions, and many rattlesnakes. When a rattlesnake got into the house, it was my older brother's job to kill it with a shovel. He would whack off the head and the body would writhe around. I would stand behind him, holding my mother's hand, watching with fascination.

"Don't play with snakes," my mother would constantly remind me. 

Alas, sometimes we have no choice.

I’ll update you in a couple of months. Please accept my apologies for any emails that have gone unanswered. I have had to leave many important things by the wayside to make time to deal with the essential.

Revlimid, the Klopman Diamond

There’s an old joke about the Klopman Diamond. It goes something like this:

A businessman boarded a plane to find, sitting next to him, an elegant woman wearing the largest, most stunning diamond ring he had ever seen. He asked her about it.

"This is the Klopman Diamond," she said. "It is beautiful, but it's like the Hope Diamond; there is a terrible curse that goes with it."

"What's the curse?" the man asked.

"Mr. Klopman."

I’ve now had a year’s worth of experience with Revlimid, aka lenalidomide, and I have come to think of it as the Klopman Diamond of CLL treatments.

In my case, Revlimid is stunningly beautiful when it comes to controlling autoimmune hemolytic anemia, reducing absolute lymphocyte count, and increasing hemoglobin and platelets. It even does a respectable job of reducing lymph nodes. This is pretty much what any CLL patient could want, especially one who has had several other treatments.

But it comes with a curse: unpredictable side effects that in my case have a little too much to do with clot formation. Not for me the simple neutropenia that bedevils many patients, or just the tumor flare and fatigue I reported early on. I get the full Klopman –- i.e. the prospect that some kind of clot will do some kind of damage that I really won’t like.

Presumably the lady with the diamond stays with Mr. Klopman because he provides so well. And so it is with me and Revlimid. It’s a rocky marriage. Happy overall, but punctuated with incidents that create a certain degree of apprehension.

*  *  *

After a year of being on Revlimid most of the time, it’s time for a trial separation. I went off the drug on March 15 and plan to stay off until I need to go on again. It’s time to give my body a rest.

That was my oncologist’s take at a recent meeting, and I agree. There’s no proof that staying on constant Revlimid maintenance (at 5 mg daily) will be better than starting the drug again when I begin to relapse. Patients are handled both ways by leading CLL centers, and this seems to have a lot to do with the guesswork of doctors and the drug tolerance of patients.

In my case, given my proclivity for clot-related problems, there is potentially some value in the “rest” theory. As you may recall, the blood thinner warfarin (Coumadin) was added to my regimen following a TIA, or transient ischemic attack. This started at 2 mg daily. It was increased to 4 mg three days a week, 2 mg four days a week as my PT/INR tests continued to show that I was clotting quickly, like someone who was not on the drug. Even at the higher dose there’s been no improvement in clotting time. Apparently I have a somewhat supernatural ability to clot, which is not useful when taking Revlimid.

I went off Revlimid at a high point. My latest CBC confirms improvement in hemoglobin and platelets that I first reported in my post of February 20. My lymph nodes have reduced nicely; I have lost five pounds since going off the drug and the nodes have gotten smaller. I’m sure that’s not all lymph node weight I’m losing. But I do think it again proves my theory that when on the drug I am in a constant state of tumor flare; off the drug, the nodes reduce to baseline.

I’m not sure they’re at baseline yet. What I can say is that they are definitely improved over a year ago. Without a CT scan I can’t put a number on it. But the nodes I can feel in my neck and under my arms are significantly smaller and a large mass under my right arm has broken up. My abdomen is noticeably slimmer. If I were forced to guess, I'd say the reduction has been up to 50% in some areas, and I'm a very nodey guy.


* * *

After I was diagnosed in 2003, I participated in online discussions about whether chronic lymphocytic leukemia could someday be controlled as a chronic disease, much as diabetes is. It seemed like a pleasant fantasy at the time. What, we wondered, if there was a pill we could take to keep the disease in check?

Today, this might be closer than we could have imagined. Might Revlimid be it? Might CAL-101?

And to what extent will we have to take our chances with Mr. Klopman? 

Only time and trial will tell.

Hemoglobin deja-vu

Periodic CBCs are routine for us CLLers, and they sometimes come with surprises, usually not good ones. For the last year my CBCs have been decent, stable, and dull, but my latest required a double-take.

My hemoglobin was 15.6, up from 13.0 six weeks before. It had been in the 13s since shortly after I began taking Revlimid (lenalidomide) on March 6, 2010. (Yep, the one-year anniversary approaches. I’m thinking of celebrating with a chocolate cupcake topped with white Revlimid pills as sprinkles.)

It turns out that the last time my hemoglobin was that high was in May 2006.  In fact, on the day I was diagnosed with chronic lymphocytic leukemia -– September 3, 2003 -– it was 15.6. The highest it has ever tested out at is 15.8. So something good is happening in hemo-land.

This is especially encouraging since autoimmune hemolytic anemia (AIHA) has been an almost constant drain on my hemoglobin since early 2007. I take this latest result as a further sign that Revlimid has put a stake through its heartless little heart.

Of course, absent AIHA, CLLers also face the challenge of their bone marrow clogging up with CLL cells, with a resulting gradual decline in red cell production. The NCI guidelines define hemoglobin below 10.0 as the welcome mat into Stage 3 CLL and one of the triggers for treatment. Where my hemoglobin would be absent both the Revlimid and my history of AIHA, I haven't a clue. But seeing it at the same place as it was at diagnosis does provide a not-so-cheap thrill. Maybe I'll have two of those cupcakes.

My test also showed higher platelets. Over the course of my CLL history, they have gradually declined. For the last couple of years they have generally been at about 130. The latest test puts them at 160. Platelets can jump for any number of reasons. For example, they can be sequestered in the spleen and treatment can reduce the spleen, forcing them into the bloodstream. In this case, I doubt my spleen has suddenly become smaller.

So the big question is: Is Revlimid having a positive effect in my bone marrow?  A 2008 MD Anderson study of Revlimid in 44 relapsed and refractory patients reported that 26% experienced “resolution of bone marrow involvement.” How that was tested for and defined was not described in the paper, but it is encouraging nonetheless. I am also aware of patients who are on the drug for a long time and begin to experience, at a certain point, the “kicking in” of improving numbers.

I’ll have to see if the trend continues on future tests. After all, one test is interesting, two are a trend. But I have no reason the believe the test is wrong. I’ve been napping a lot less recently, even when I’ve had less than eight hours of sleep at night, which would be one result of higher hemoglobin. And not all the numbers are higher, so it’s not like the blood counting machine was ascribing a higher count to everything. (My absolute lymphocyte count remains pretty stable at 6.24.) This test was done at the same lab that I've been using for the past year.

Finally, on the Coumadin (warfarin) update front, my dose has been bumped up slightly. It’s now 4 mg on Monday, Wednesday, and Friday, 2 mg on other days. This came after my PT/INR tests continued to show that I clot faster or the same as normal even though I’m on the blood thinner. My Revlimid dose is now 5 mg five days a week, 10 mg on Wednesday and Sunday. It probably won't go any higher for the foreseeable future. 

And now, the bad news

“Laws are like sausages,” Otto von Bismarck once said. “It is better not to see them being made.”

The same could be said of treatments for chronic lymphocytic leukemia, especially with experimental drugs like Revlimid, aka lenalidomide.

Not long ago, I wrote about some of the positive aspects of my Revlimid experience in a piece entitled "First, the good news." Now it’s time for the promised bad news, which happened in October while I was trying to increase my daily dosage from 10 mg to 15 mg and then 20 mg.   

Actually, the first sign of trouble was back in June, when I was taking 10 mg. One night, all of a sudden, I had trouble forming sentences. I could talk or write, but as I did I realized that I wasn’t saying the words I meant to say. Language is usually reflexive, but I found myself having to concentrate very hard to find the right words to form even simple sentences. I was not always successful. This lasted for about 10 minutes and stopped almost as suddenly as it had started.

I think many of us experience some loss of mental agility with age, an effect of which can be occasionally searching for words (as well as standing in front of the pantry blankly and saying “Now, why did I come over here?”). Revlimid can further (temporarily) reduce this agility by adding a layer of dullness or lack of mental swiftness. In the past I have described the drug as the enemy of multitasking.

My ten-minute word hiccup seemed similar to things I had experienced as part of aging, but also different enough and intense enough to cause me concern. I took myself off the drug immediately and looked at the list of side effects that the drug's maker, Celgene, provides. I also read up on side effects reported in CLL and Revlimid studies. Nothing obvious seemed to explain the situation, so I chalked it up to “chemo brain,” a medical catch-all that is not unlike that famous Victorian malady, “the vapors.” I resumed the Revlimid after a few days, and all was well. By the time I next saw my oncologist, I had almost forgotten about it, mentioned it in passing, and went on my merry sausage-making way.

MORE SAUSAGE

Until it happened again, on the night of October 5, four days after I began taking 20 mg. Again with the language problem, again for about 10 minutes. Marilyn said it sounded like I was trying to say two things at once. I recalled getting words almost right; for example, I wanted to say “tea” but ended up saying “Ted,” which is my father’s name. Hey, both start with a “T” and have three letters!

This time I didn’t shine it on. While on 15 mg for two weeks, I had begun to hear a periodic heart beating sound in my right ear. This got worse at 20 mg. Before the language problem hit, I had already decided to stop the Revlimid that night and have a CBC the next day. In the past, whenever I had heard a heart beating sound, it had signaled hemolysis, or an attack of autoimmune hemolytic anemia (AIHA), in which the body destroys its own red blood cells. This sound was different, though, and I wasn’t getting any other telltale signs of AIHA, such as orange urine or feeling winded while walking up stairs. Still, I didn’t want to take any chances, and a CBC seemed a logical place to start.

The CBC came out fine. All I knew for sure is that the severity and frequency of the beating sound had increased with the dosage of Revlimid and that the sound went away when I was off the drug. And, of course, I had that disturbing language thing again. I made an appointment to see my oncologist, Dr. Belle, ASAP.

Dr. Belle told me that Revlimid increases the viscosity of the blood and that the sound was probably my heart working harder to pump blood into my brain. This explained why the sound got worse with the higher dosages.

And this also explained the language trouble: Dr. Belle said I had almost assuredly had a TIA.

A what, I asked?

“Transient ischemic attack,” she said. Also known as a mini-stroke.

“I’m quite concerned about that,” she said.

I was, too. Later, after making use of Google to find out everything I could about TIAs, I was in something of an information-induced panic, after which I calmed down to a level that might be described as “heightened concern.” 

I learned that TIAs, like full-fledged strokes, are caused by a blood clot in the brain. The difference between a TIA and a stroke is that a true TIA lasts less than 15 minutes and causes no permanent damage.

TIAs can affect vastly different areas of the brain, including language (leading to expressive aphasia in my case, where I can understand what is being said but have trouble expressing myself). TIAs are considered to be warnings; about one third of people who have them go on to experience a full-fledged stroke within a year.

Should the ischemic attack drag on for more than an hour, you enter the realm of official strokedom and potentially severe harm. I had narrowly missed a situation in which I might have ended up bawking bike kiss for the guest of by wife.

YOUR FRIEND AND MINE, COUMADIN

Before these incidents, I had never had a stroke or a TIA. The literature on Revlimid and CLL indicated that blood clots in the lungs and legs could be an issue, but I could find no evidence of TIA in CLL, although it was reported at least once in  patients taking Revlimid for myelodysplastic syndrome.

Apparently, a TIA is a rare event, although clots are not. One patient information document for a Revlimd-CLL clinical trial classifies clotting -– defined as “formation of a blood clot that breaks loose and is carried by the blood stream and plugs another vessel” -– as one of a secondary group of possible side effects of Revlimid, occurring in 3% to 20% of patients. 

The trial, using Revlimid as a single agent, is being conducted at New York’s Roswell Park Cancer Institute, arguably the country’s leading center for CLL-Revlimid research. They have been dealing with CLLers for years and have the clinical experience to know what’s what.

And guess what?

All patients in the trial -– yes, ALL–- are required to take 2 mg of the blood thinner Coumadin each day.

This, my friends, is not commonly known, and it’s not even commonly practiced in most other CLL-Revlimid trials, from what I can gather. Nor is your local oncologist likely to know about it. So consider it a public service when I say that it is a wise precaution for all CLLers, even those with no history of clotting problems, to take Coumadin (generic warfarin) with their Revlimid!

As the patients in the study are told in writing: “It is important that you take the Coumadin every day that you take the study drug lenalidomide.” (Here's an interesting little abstract.)

Obviously, those who are at high risk for clotting stand a better chance of running into trouble. But how do you know if you’re high risk?

I had no history of clots. My blood pressure is excellent, I don’t have diabetes, arterial disease, or high cholesterol. High risk? Me?

Then I had a grand “D’oh!” moment, worthy of Homer Simpson at his worst.

Back in 1977, my mother, who was only three years older then than I am now, died of a pulmonary embolism. She had a long history of thrombophlebitis, or veins being blocked by clots. My older half brother, her other son, had two strokes about ten years ago -– when he was the age I am now -– after using Vioxx. He had assumed that Vioxx, later recalled by the FDA, was the cause. But did heredity play a part, especially since he had another stroke just a few months ago? Even Homer Simpson could probably get the right answer to that one.

PROCEEDING CAUTIOUSLY

I’ve been back on 5 mg of Revlimid, as well as some Coumadin, for awhile now. A carotid ultrasound ruled out any problems with plaque in the neck, so the odds of another TIA (or worse) really seem dependent on the dose of Revlimid I take, as well as the dose of Coumadin.

After two weeks of 2 mg of Coumadin daily, I had a PT/INR test, which measures clotting time. Mine came out normal. In other words, I was clotting like a person who wasn’t on Coumadin. That’s just not a good sign. So now my doctor is fiddling with increased dosages, which is typical with Coumadin, trying to get my blood suitably thin.

Until that’s done, I’m sticking with 5 mg of Revlimid. I may never go higher, and I may end up using the 5 mg intermittently -– say three weeks on, one week off, or 5 mg every other day.

The 5 mg seems to be working fine, judging by how I reacted when I resumed the drug after a three-week treatment holiday. I got a good amount of tumor flare, which lasted about two weeks before reducing, and my B2M is high, indicating that a whole lot of cell kill is going on. My CBCs continue to be normal and I have so far been spared the low neutrophils and low platelets that are fairly common to CLLers on Revlimid. 

Needless to say, I’m going to watch for symptoms very carefully. Should I experience a third TIA, despite the blood thinner, my Revlimid career will probably come to an end.

Why take a chance at all, you might ask? Well, I don’t really have a choice. That's a short sentence but a big concept. Sometimes we take risks because we have no better alternative. Revlimid is the only thing out there that appears to be able to give me long-term stable disease without the curse of AIHA.

Other therapies also come with potential for great harm, just in different form, in case you hadn’t noticed. I'd rather take my chances with carefully managing Revlimid at lower doses -- which may get me to the next drug that can control my disease but might be easier on the system (CAL-101?) -- than jump on the transplant bandwagon. Given the difficulty I would face in getting a good donor match, as well as the inherent risks that can lead to fatality, I am in no rush to go that route. 

With CLL treatment, we are always playing with fire. At least I now know what I need to watch for and plan for. The only thing worse than having to manage potentially serious side effects is to suffer them without warning.

I’ve been warned.

Revlimid dosing

One thing I'm learning about Revlimid and CLL is that it's a bit like the Wild West. There aren't a lot of rules, you can strike it rich or get gunned down, and you'd better be a little tough to survive what life throws at you. A shot of whisky now and then doesn't hurt, either.

Deciding on a dose (of Revlimid, that is) and how frequently to take it is a particularly open-ended subject. In one clinical trial, the goal is to get patients up to 25 mg per day, if they can tolerate it. Another study suggests that 2.5 mg to 5 mg may be the maximum tolerated dose for heavily pretreated patients. Based on reported data, Celgene Corporation, the maker of the drug, advises that more than 10 mg is potentially unsafe for CLLers. And now there's an abstract out about pulsed dosing in relapsed patients that suggests 20 mg is more effective than lower doses.

The study was done at the NIH and an abstract was presented at the recent American Society of Hematology meeting. Patients were given Revlimid three weeks on and three weeks off. Thirty-one patients had at least two cycles of therapy, which is a short period for Revlimid. Some had as many as eight, but the abstract does not address the median number, which is significant in that Revlimid can require long exposure for the best effects. 

At any rate, there were no CRs; 16% had PRs, 58% stable disease, and 26% progressive disease. Of the five patients who achieved a PR, four had deletion 17p and bulky disease. Four of that five started Revlimid at 20 mg; one started at 10 mg. Pulsed dosing did not lead to fewer toxicities. Once treatment was stopped, median time to next therapy was  six months, although it ranged from two to 18 and was significantly better in the PR group. The full abstract is well worth reading and can be found at the bottom of this post as well as, hopefully, through the link.

There is no "written in stone" rule about Revlimid dosing, but something of a consensus may be emerging. Based on the NIH study and other data, not all of it published, we do seem to be learning that the highest tolerable dose (up to 25 mg) may be most effective. But getting there can be a rocky road, pardner, which I will blog about within the next few weeks. Celgene is not wrong to suggest that the higher you go, the more trouble you may get into. 

And staying there, or staying at any dose level, is not guaranteed. Side effects -- low neutrophils, low platelets, serious rash, blood clots, etc., etc. -- can derail the Revlimid train.  As the NIH study points out, Grade 3 or 4 neutropenia was seen in 56% of cycles, "often worsening in continuing cycles." One thing we do know for sure about Revlimid is that individual response can be unpredictable, both in terms of effectiveness and side effects. 

Revlimid is effective in many patients who have become refractory to other drugs, but can you become refractory to Revlimid? Apparently, yes, from what I've heard, although I don't think there have been any studies on the subject. This has happened to some patients, mostly those who have been heavily pretreated. Why this happens to some and not others, and whether it has something to do with dosages and treatment schedules, is unclear.

For those of us who achieve a remission or stable disease with the drug, how do we maintain it? Again, there's nothing set in stone. In one leading center they keep you on the highest dose you can tolerate for a year, then take you off. You're monitored and only resume Revlimid again when you begin to relapse. There aren't reports of patients becoming refractory there, so perhaps this method has a hand in maintaining the drug's usefulness.

One fascinating question is whether the Revlimid can actually train the immune system to attack CLL cells on its own, without the Revlimid. This possibility has been suggested by some serious people, but it will probably be a long time before we see any hard data.

Basically, there's still a whole lot of guessing going on when it comes to how much to take and how often. The advantage of taking more, namely better response, can be offset by worsening side effects.  And, of course, one patient can do well on 5 mg when another really needs 15 or 20 to show progress.

Revlimid, like exploring unknown territory, requires that your eyes and ears be open. Back in the old days, not all maps were drawn, and not all were accurate. If you're on Revlimid, you're a trailblazer, like it or not. 


Phase II Trial of Pulse Dosed Lenalidomide In Previously Treated Chronic Lymphocytic Leukemia


Georg Aue, M.D.1, Susan Soto, RN2*, Janet Valdez, PA1*, Diane C Arthur, M.D.3, Xin Tian4* and Adrian Wiestner, M.D., Ph.D.5

1Hematology Branch, National Heart, Lung, Blood Institute,, National Institutes of Health, Bethesda, MD
2National Institutes of Health, Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD
3Laboratory of Pathology, NIH/NCI, Bethesda, MD
4Biostatistics, National Heart Lung and Blood Institute, Bethesda, MD
5Hematology Branch, National, Heart, Lung, and Blood Institute, Bethesda, MD

Introduction: Lenalidomide (L) has activity in relapsed chronic lymphocytic leukemia (CLL). The mechanism of action is not well understood but may involve stimulation of anti-leukemic immune responses. Myelosuppression especially neutropenia is a concerning side effect. We reasoned that pulsed dosing of lenalidomide could reduce myelosuppression while maintaining the immune stimulatory effect. To test this concept we initiated a single center, phase II trial (ClinicalTrials.gov Identifier: NCT00465127) of lenalidomide given in cycles of 3 weeks on, 3 weeks off drug (42 day cycles).

Methods: Patients (pts) with relapsed CLL or small lymphocytic lymphoma with ANC>500/ul and platelets >20,000/ul were eligible. The primary endpoint defined as response after 4 cycles has been recorded for all participants. Pts with partial response were allowed to receive up to 4 additional cycles. The starting dose for the first 10 pts was 20 mg daily; the starting dose for pt 11 onwards was lowered to 10 mg daily because of toxicities observed in other L trials for CLL. TLS prophylaxis with Allopurinol was mandated during cycle 1-3. Deep venous thrombosis (DVT) prophylaxis was not mandated unless risk factors were present. Ibuprofen and corticosteroids were allowed to treat symptoms of a cytokine release syndrome (CRS, defined by LN swelling, fever, fatigue, pain, chills, dehydration). Responses were assessed by IWCLL criteria and included CT scanning.Patient characteristics (n=33) were: median age 64 years (36-78); median number of prior therapies 3 (range 1-7); 52% Rai stage III-IV; 70% bulky disease; 30% fludarabine refractory; 56% (of 27 pts) ZAP70 pos; 64% (of 25 pts) unmutated immune globulin VH mutation status; 43% del 17p; 15% del 11q.

Results: A total of 131 cycles of L were given. 31 pts received at least 2 cycles of therapy (range 2-8) and were evaluable for response: 5 (16%) partial response (PR), 18 (58%) stable disease, and 8 (26%) progressive disease. 4 of 5 responding pts had del 17p and bulky disease. In responders (n=5, PR) vs non responders (n=26, SD+PD) the PFS was 16 vs 6 months (p>0.01), and the time to next therapy was 17 vs 6 months (p>0.01), respectively. Once treatment was stopped, duration of response was short lived (median 6 months, range 2-18). 4 out of 5 responders were observed in the 20 mg dose starting group versus only 1 responder in the 10 mg group (p=0.03). There was no difference in the CRS score between the 2 groups (2.5 vs 1.5, p=0.17). Hematologic responses were observed in 11 out of 24 CLL pts (45%). At the completion of 4 cycles CD4 and CD8 counts increased by 20%, while NK cell counts remained unchanged. Dose modifications/withdrawl: 41% of cycles required dose adjustments prior to or during cycles 1-4. 9 pts (27%) did not complete 4 cycles of L because of: autoimmune cytopenias (2 pts), side effects (4 pts; CRS 1 pt, neutropenia 3 pts), withdrawal from study (2 pts), and disease progression (1 pt). Toxicity: Gr 3/4 neutropenia was observed in 56% of 131 cycles, often worsening with cumulative cycles. Gr 3/4 thombocytopenia and anemia were seen in 30% and 15% of cycles, respectively. Gr 1/2 and 3/4 infections occurred in 23% and 11% of cycles, respectively, 8 of those in the setting of neutropenia. Gr 3 CMV colitis, PCP pneumonia and Candedemia each were observed once. 1 patient died from streptococcal sepsis in cycle 4. Gr 1/2 and 3/4 CRS were observed in 43% and 10% of cycles, respectively. A CRS was encountered in 78% of first cycles typically within the first week, and in 48%, 38% and 30% of cycles 2-4, respectively. 6 DVTs (Gr 3) were diagnosed in 5 pts. Other common side effects were fatigue (62%), rash (39%) and muscle cramps (27%), all Gr 1/2. No case of tumor lysis syndrome was seen.

Conclusion: L cycled 3 weeks on, 3 weeks off led to stable disease in the majority of pts and induced PRs in 16% of relapsed CLL patients with high risk disease. Pulse dosing of L did not lead to reduced toxicities. Myelosuppression and infections remain a major concern. 4 out of 5 responders were observed in the 20 mg cohort arguing for higher L starting doses. Notably, side effects, particularly the CRS, were similar in the two cohorts. Once L was discontinued, the duration of response was short, suggesting a need for continued therapy in pts who are able to tolerate the drug.

Disclosures: Off Label Use: Lenalidomide is not FDA approved in Chronic Lymphocytic leukemia.

The OL Protocol: Early results from MD Anderson

For the record, some results have come in from MD Anderson on the Ofatumumab and Lenalidomide trial that I was following from afar. My doctor and I decided to drop the "O" after September's infusion because it didn't seem to be particularly effective. The Lenalidomide, however, is doing me a fair amount of good.  (A reminder: the "L" is Revlimid, the "O" is Arzerra.)

The protocol, discussed in an abstract presented at the just-concluded American Society of Hematology conference, is providing good results for 10 of 16 relapsed, refractory patients. There have been two CRs and eight PRs. Four patients with stable disease are continuing in the study. One patient's disease progressed, and one patient dropped out. 

By comparison, I  would probably qualify as having stable disease since I don't fit all the definitions of PR at this point. This is mainly due to disease bulk, which is still extensive, although moving in the right direction. It needs to show a greater than 50% reduction, and I'm probably at about 33%. (Click here for a PDF of the guidelines by which types of remissions are defined).

Here's the abstract in its entirety (paragraph breaks added by yours truly since most doctors can't write):

Combination of Ofatumumab and Lenalidomide In Patients with Relapsed Chronic Lymphocytic Leukemia: Initial Results of a Phase II Trial

Xavier Badoux, MD, Susan O'Brien, MD, William G. Wierda, MD, PhD, Stefan Faderl, MD, Zeev Estrov, MD, Kimberly Yerrow, BSN, Hagop M. Kantarjian, MD, Michael J Keating, MD and Alessandra Ferrajoli, MD

Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston, TX

Frontline chemoimmunotherapies induce high response rates in patients with CLL. Once disease recurs, however, effective treatment options are limited and new therapeutic modalities and combinations are needed. Ofatumumab is a fully humanized anti-CD20 monoclonal antibody which produces an overall response rate (ORR) of 47%-58% in patients with fludarabine-refractory CLL (Wierda W. et al, 2010). Lenalidomide, an immunomodulatory agent, induces an ORR of 32-47% in patients with relapsed/refractory CLL, (Chanan-Khan A.A. et al. 2006; Ferrajoli A. et al. 2008).

The rationale for combining ofatumumab and lenalidomide is based on their single agent efficacy, distinct and potentially complimentary mechanisms of action and non-overlapping toxicity profiles. Furthermore, the combination of lenalidomide and rituximab has shown significant activity in patients with relapsed disease (Ferrajoli et al. 2009). We, therefore, designed a phase II study to evaluate efficacy and tolerability of ofatumumab and lenalidomide given in combination in patients with relapsed CLL.

Patients with active disease were eligible if they had received prior treatment with purine analog-based therapy, had an ECOG/WHO performance status of 0-2, adequate renal (creatinine clearance > 30ml/min) and hepatic function (total bilirubin < to 2 mg/dl and ALT < 2 X ULN). Patients with any neutrophil count were eligible, whereas patients with platelet counts < 30,000 mm3, positivity for HIV, active hepatitis B or C or recent history of tuberculosis were excluded from participation.

In this trial ofatumumab is administered intravenously weekly for four consecutive weeks (300mg week 1, 1,000 mg week 2 and all subsequent doses), then monthly for months 2-6 and once every two months for months 7-24. Lenalidomide is given orally at the dose of 10 mg daily, starting on day 9 and continued daily. Allopurinol at the dose of 300mg daily is given during the first two weeks of treatment as tumor lysis prophylaxis. Treatment duration is 24 months, and responses are assessed after 3, 6, 12, 18 and 24 months of therapy.

Thus far 26 of the 40 planned patients have been accrued to this study and we present an analysis of response and toxicity for the first 16 patients that have been on study for at least 3 months. The median age of the patients is 62 yrs (45-82). Eight patients (50%) had Rai stage III-IV disease. The median Beta-2M level was 4.4 mg/dL (2-6.1). The median number of prior treatments was 2 (1-8). Four patients (25%) were refractory to fludarabine and all pts had received prior rituximab. Nine patients (56%) had unmutated IGHV genes, 5 patients (31%) had chromosome 17p deletion and 3 patients (19%) had 11q deletion as detected by FISH analysis.

Responses were evaluated according to the 2008 IWCLL criteria: 10 of the 16 evaluable patients achieved a response [2 CR (13%), 8 PR (50%)] for an ORR of 63%. Four patients with stable disease are continuing on treatment. One patient discontinued therapy and did not return for response assessment and another patient progressed. All patients are alive.

The most common grade 3-4 treatment related adverse events observed were: neutropenia (8 pts, 50%) and anemia (2 pts, 13%). One patient (6%) developed grade 2 superficial vein thrombosis. Lenalidomide-associated tumor flare reaction was limited to grade 1 in 2 patients (13%) while a grade 3 infusion reaction was observed in 1 patient (6%) during the first ofatumumab administration. Three grade 3 infectious episodes occurred: 2 cases of pneumonia and 1 case of parotiditis. None of the patients received routine antibiotic prophylaxis. The median daily dose of lenalidomide tolerated was 5 mg/day (2.5-10 mg).

In conclusion, our initial analysis indicates that the combination of ofatumumab and lenalidomide is therapeutically active in patients with relapsed CLL. This treatment is well tolerated. Neutropenia is the most common toxicity observed. Enrollment is ongoing, and updated results will be provided.

Disclosures: Off Label Use: Ofatumumab and lenalidomide in patients with relapsed chronic lymphocytic leukemia. O'Brien: GlaxoSmithKline: Consultancy. Wierda: GlaxoSmithKline: Honoraria, Research Funding; Celgene Corporation: Consultancy, Membership on an entity’s Board of Directors or advisory committees. Estrov: Celgene Corporation: Consultancy. Keating: Celgene Corporation: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria. Ferrajoli: Celgene Corporation: Research Funding; GlaxoSmithKline: Research Funding.

First, the good news

When last we left off on my Revlimid journey, I was planning to increase my dosage from 10 mg daily to 25.

The hope was that the higher dose would bring even more beneficial results, especially in terms of lymph node reduction. The plan was to increase the dose in two-week increments, as is done -– if the patient can tolerate it -– in a clinical trial at the leading center for Revlimid research, Roswell Park Cancer Institute in Buffalo, NY.   

All went well in the beginning. I did 15 mg for two weeks and then moved to 20. That lasted for four days, after which I was able to answer the question, “Why isn’t every CLL patient on 25 mg?” 

That’s also the “bad news” part of the story, which I will explain in detail soon. But first, there are some other things that deserve to be in the spotlight.

The big picture is that the more I use Revlimid, the more I am convinced of its usefulness. I’m in my ninth month of it, and despite the challenges involved in getting used to the drug and managing symptoms that arise, I have benefited greatly from it.  My autoimmune hemolytic anemia is gone, my blood counts are normal, and the lymph nodes are in retreat.

Tumor flare masks lymph node reduction

One thing I’ve had a hard time figuring out all along is whether the lymph nodes are reducing and by how much. You’ll recall that I had terrible tumor flare in the beginning. After doing the Revlimid Shuffle -– two steps forward and one step back -– my doctor and I  were able to calibrate the dosage so that the flare was no longer an issue. If it was there, it wasn't obvious.

Some time ago, when I was off Revlimid for five days, I noticed that my nodes got smaller. After I stopped 20 mg, I was off Revlimid for 16 days. The nodes again reduced, and kept on reducing over the entire period, which confirmed my earlier experience. This tells me that low-level tumor flare is continuous when I am on the drug, and that when I am off it the nodes recede toward their real baseline. (This is all good; tumor flare is generally considered to be evidence that the drug is working.)

To determine the actual progress I’ve made these past nine months, I would need to be off Revlimid for several weeks, after which I would need to undergo a CT scan to compare to the one I had when I started.

Since that’s not going to happen anytime soon, I am left with the second-best option, namely self-groping and educated guessing. By that measure -– and being conservative in my judgment -– I’d say the nodes are one-quarter to one-third smaller. 

As someone whose disease has become node-based over time, and who probably has more disease bulk that 99% of CLL Revlimidians out there, I cannot tell you how important it is to see such progress. 

And seeing is believing. You know you have CLL when you keep a folder of photos on your computer called "My Neck." Looking back at old photos, I can see that my neck is now as slim, on a consistent basis, as it was in 2004. The abdominal nodes are no doubt worse than they were in 2004, but I look less pregnant than I did nine months ago and have lost about 10 pounds since then. 

B2M test is a useful measure of whether Revlimid is working

Over the course of my 7-year CLL career, my B2M, or beta-2-microglobulin, has gradually risen. B2M is a protein shed by CLL cells into blood serum; the more CLL cells there are reproducing and dying, the more your disease is proliferating, the more B2M they put out. So, as a rule, the higher your B2M, the more active your disease. 

If your B2M is below 2.0, you’re considered to have “the good cancer” behaving itself. When your B2M gets past 4.0, MD Anderson says you have “the good cancer” behaving badly, which means you have less manageable, progressing disease.

Looking back on my case history, I think B2M has been an accurate measure. It was 2.2 at diagnosis in 2003, 3.0 by April 2005, 4.9 in January 2007. It has been lower, usually just after chemo has concluded and the disease is in some kind of remission. But in times of no treatment it has risen over the years, finally finding a plateau in the 4s since 2007. In June 2009, my last B2M before starting Revlimid, it was 4.5.

But there is a big caveat when it comes to B2M, During treatment, when tens of millions of CLL cells are being torn to pieces, that B2M protein can also increase in the blood. So in some cases, a high B2M is not cause for alarm. It’s a good sign.

Which brings us to August 30, when I had my first post-Revlimid B2M test. The result was a jaw-dropping 8.8. Things had been going so well. Did this test mean that the disease was progressing anyway?

After my two weeks of 15 mg and four days of 20, the B2M was 11.1. This is so high as to be almost laughable, if not also a little scary. But was it possible that the higher doses were causing more anti-disease activity, which was being reflected in the test?

Two weeks later, after I was on and off the drug and ultimately back on 10 mg, the test came out at 8.8 again.

All of which tells me that my B2M rose with treatment, increased with the higher dosages, then decreased when the dose did. At least in my case, the high B2M seems to be evidence that Revlimid is working, and is therefore jaw-dropping for a good reason.

Au revoir, Arzerra

My treatment began as the “OL Protocol,” modeled after one currently in trial at MD Anderson. The “O” is for ofatumumab, aka Arzerra. The “L” is for lenalidomide, aka Revlimid.  Arzerra is an anti-CD20 monoclonal antibody, much like Rituxan, perhaps better in some ways. MD Anderson had reported that patients treated with rituximab and Revlimid did somewhat better than patients treated with Revlimid alone.

But there has been debate about this all along. Revlimid appears to downregulate CD20 on the surface of B cells, which logically means that anti-CD20 monoclonals should have a harder time working when Revlimid is present. Alternate sequencing strategies –- say, have the Arzerra first, then do the Revlimid -– have been suggested as potentially being more effective. It’s important to remember that Revlimid is still new in CLL, its mechanism of action is not completely understood, and that we are in the trial-and-error phase.

Whatever the reason, except for one brief burst of node-reduction in May, the Arzerra never seemed to do much for me. Perhaps it’s because my CLL cells had little CD20 on them to begin with, which could be the result of using Rituxan over many years. Or maybe the stars weren’t aligned properly. Following my last Arzerra infusion in early September, my oncologist and I concluded that the Revlimid was doing the work and that the Arzerra was just expensive window dressing. So we’ve stopped it, and I’m on the “L” protocol now, which we are devising as we go along.

It appears that, so long as I can tolerate Revlimid and it continues to provide benefits that outweigh the risks -– more on that next time! –- I will be taking it for the foreseeable future.