Tuesday, February 09, 2010

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.


Anonymous said...

Hooray for you, David! I'm so glad it worked out for you!

Please keep us posted, when you can.


Anonymous said...

David - You are my a true hero! We are the same age and I have followed your bluntly informative - yet entertaining - CLL story. I am a few steps behind you in treatment and I look forward to reading your next chapter as you venture into this new trial for the CLL community. I appreciate your going down this new street. I will be following you.... Keeping you close in my thoughts.

Anonymous said...

Thank you, David - for all you do for our community. We will be looking forward to reading your posts and sending the most positive thoughts your way. You have the knowledge to make good choices for yourself and I know this will be a touchdown - and extra point!!

Anonymous said...

Great writing,once again, David. Thanks for that. I will be thinking of you as you start your treatment tomorrow. Hopefully, this protocol will bump you back several years to a better CLL place. As you know, Tom was one of the stable and then failure rats on the Revlimid/Rituximab trial at MDACC. His reaction was in the form of allergy to Revlimid. Dr. Keating told him, "If you can take it, you can make it." That seems to work for a lot of relapsed patient's, just not for Tom. The upside is that HuMax is working very well for Tom. So, if you can adjust to taking both, well......we just might see a managed disease for you! And I feel that managing CLL is a better game then trying to manage GVHD and the odds of all the stuff that comes with a transplant. But, like you, we know that it might be the last hope for Tom soon. Before HuMax, (which MDACC calls a band-aid treatment for Tom), a transplant looked like it might be in a couple of month's....now, Tom is getting the chance to wait for the next trial at MDACC which will be true genetic tweaking....let's hold on if we can....Dr. Keating actually stated that he believed a cure would be here in 5 years or less that would not involve a transplant like the one's we see now. Genetic treatment is coming....sooner than later, I hope.

I will read every update----just remember that the fatigue leaves after 3 months and new energy takes it's place.

Jenny Lou

Anonymous said...

Good stuff, David. I have hairy cell leukemia, which is definitely not going to kill me, but at my age I just can't have the really toxic stuff going into me. That's what would kill me eventually. Nine years ago I went into a clinical trial at MDA for Rituxan (Keating was my doc), and I was hoping Humax CD20 would be Rituxan on steroids. Apparently, in cases other than CLL, it's not the silver bullet, but your posting is informative and useful to me anyway.

Also, I would second your advice to never let your doctors rush you. Initially I had a doctor who, when the chemo failed, wanted to chemo again. We're talking major state teaching hospital here. Some lesson! We fired him and found an oncologist who recommended going to MDA for treatment. Best thing we ever did.

~chris said...

Right On David!

Glad to see your views on transplants. I have always maintained that anyone considering a stem cell transplant, sit down for an hour with a patient that has chronic GVHD.

Then make a decision.

momr said...

Go David...my prayers, karma &good thoughts are with you and M on the next adventure...Kick it!

Anonymous said...


I started seeing Dr. Alessandra Ferrajoli as my doctor about three years ago after finding the doctors in the Seattle Area not always on the cutting edge of new CLL drug studies. I am a CR veteran of FCR with GMCSF about a year ago and am still in remission. She is a wonderful person and her crew are the best I have seen.

I have been reading your blog for about three years and have found it extremely educational on managing treatment.

Best of luck in Houston!

James Swanson
Snohomish, WA

David Arenson said...

Thanks for all the encouraging comments!

James, I will be following the MDA protocol, just not in Houston. I can't qualify for that trial as I have not yet had therapy with purine analogues (i.e., fludarabine). So we're doing it at my oncologist's office in Scottsdale.

There has been a one-week delay in the start of my tx. I came down with a cold on Tuesday, the day before I was scheduled for my first dose (300 mg) of ofatumumab. I'm pretty much over the cold now, so we'll be starting next Wednesday. When I say cold, I am referring to something that has a bacterial component, since augmentin appears to be key to my recovery.

Anonymous said...

My gosh you write long posts!

R&R has been effective in some people, but the CR rate has been low. Arzerra may help, but it is a potent drug with more side effects than rituximab.

For what it's worth, Keating is 'keen' on everything. I think he is over-optimistic.

A transplant is the only way to a cure. You'll never be in as good of shape as you are now.

Anonymous said...

Good luck David! I also want to say that you have quite a great doctor! Wish we could see her too! Beth in Oregon

Heather said...

Hi David!

Thanks you for sharing your experiences! My Mom has CLL, 11q deletion for 4 years now. Every treatment has failed. I forwared your blog to her Dr at Johns Hopkins. We started her on Revlimid..Keeping our fingers crossed. Running out of options. Thanks again for telling your story. Hope to hear soon how you are doing! Heather