Saturday, May 4, 2013

Non-Chemo Approaches to CLL in and out of Trials: Lenalidomide

Avoiding chemo, especially when it doesn't cure any of us with CLL/SLL, has always made good sense. My readers know my mantra of protecting our bone marrow and immune defenses for the long term battles aheads again against infections and secondary cancers.

Now with the promise of the approval of all these new agents in sight, many CLL gurus (Kipps, Keating, Byrd and others) hail the twilight of chemo as frontline treatment. Today there are even more reasons to consider non-chemo " bridge therapies" to buy us time until the magic CLL slayers are approved or there is a trial open that accepts someone with our profile (not always easy).

Besides the short term misery of the side effects in the infusion center and for the weeks that follow, why put ourselves at increased risk for secondary cancers (especially other hematological malignancies), bone marrow damage with resulting cytopenias (low blood counts), infections, and maybe even an increased risk of auto-immune issues. If we can hang on for a year or two, we can get a much less toxic therapy from our drugstore, assuming we can find a way to pay the $10,000 or more a month cost, but that's another subject. See my friend, Dr. Jeff Sharman's blog at http://www.cll-nhl.com/2013/05/how-expensive-are-new-drugs.html?m=0 for a nice discussion of that issue.

The good news is that there are already several good non-chemo options available in trials or in the clinic, for use as single agents or in combinations.

Over the next few weeks I will offer up several for your consideration.

I will start with an old friend, one of the choices that is both on the market already and available in some interesting trials.

Lenalidomide (Revlimid), an immunomodulator, is approved for multiple myeloma (MM) and some special cases of myelodysplastic syndrome (MDS). In CLL, the NCCN recommends it as 1st line therapy for those over 70 or sicker younger patients with co-morbidities. That can help you get it off label and with a little bit of effort, have your insurance to help pay for it. At an estimated $425 for each daily 10 mg tablet at Walmart that translates to more than $150,000 per year, we all need some help.

That is one real unsung advantage to a clinical trial: the trial drugs are free.

And Revlimid is also available in several promising trials for CLL. There are two in particular that are very much alike that have me excited: NCT01766583 and NCT01732861 where it is combined with a very specific BTK inhibitor (CC-292 AKA AVI-292 or AVL-292) that is behind the leader of that pack in development, ibrutinib.  More on that drug later. Both of these trials are for those with relapsed or refractory disease.  Read the details. Call the co-ordinator. Become your own expert.

If you go on to http://clinicaltrials.gov/ct2/results?term=lenalidomide+CLL&Search=Search you'll find an impressive list of 75 different trials with lenalidomide for CLLers. Many of these are closed or not recruiting, many are in combo with chemo, and many have restrictive inclusion and exclusion criteria, but take a look and you may find something that fits your need to control the CLL.

Lenalidomide has several advantages. It is an oral medication. It may work better the longer you take it. It is an IMiD that modulates the immune system, and CLL is a disease of the immune system. It doesn't damage DNA or target rapidly dividing cells as does most chemo. It make sense that it might boost the efficacy of other therapies from vaccines to rituximab (AKA R+R), steroids and more.

And as I said, it's not "chemo.

Not that it a free ride. It can suppress blood counts especially neutrophils and platelets, increase infection risk, cause a nasty and potentially dangerous tumor flare and tumor lysis syndrome, make us very sleepy, increases the risk of dangerous blood clots, should never be taken if you could get pregnant (it is closely related to thalidomide that also works in CLL) and it has been associated with more secondary cancers.

Still, today, I definitely sees many circumstances where I would take it ahead of the gold standard, FCR or the new hottie, BR.


Do your homework and check it out.

More soon on other non-chemo options including new and old TKIs and the next generation of MaBs and others.

Also part two of the Wiestner interview from ASH and more details on my recent visit to OSU.

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5 Comments:

Anonymous K. Reale said...

Brian,

Thanks for keeping us updated, informed and empowered. I am grateful for your tireless efforts and your constant inspiration.

Kind Regards,
K. Reale

May 5, 2013 at 9:08 AM  
Blogger early 60s professional living in Jersey exurbia said...

Brian
One other issue with Revlimid is secondary cancer, see http://www.myelomabeacon.com/news/2012/05/07/fda-issues-extensive-update-about-revlimid-lenalidomide-and-second-cancers/

May 5, 2013 at 12:14 PM  
Anonymous Anonymous said...

Nice for those who were able to avoid chemo, not so good for us who were victims of MD Anderson's push to get everyone on FCR.

May 5, 2013 at 2:44 PM  
Blogger Brian Koffman said...

To pro from Jersey,
Agree with more secondary cancers. Pointed it out as one of the problems in my post.
Stay strong
Brian

May 5, 2013 at 11:01 PM  
Anonymous Anonymous said...

I've been on lenalidomide since December of 2010 with outstanding results. Tumor flare management can be tricky at the beginning of treatment, which may limit the application of this drug beyond CLL specialists, but if you are one of the patients who responds then there can be a long, deep remission with very few side effects.

From what I have read, the secondary cancers associated with lenalidomide have all been observed in MM patients who were heavily pre-treated with melphalan; a distinctly different profile than that of most CLL and NHL patients who are receiving it.

May 6, 2013 at 8:48 AM  

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