CC-122, a new IMID or immuno-modulator in trials for CLL (chronic lymphocytic leukemia)

Stairs to the beach at Torrey Pines State Park

Hi friends,

This week in the Beyond the Basics/Treatment section of our website, we’ve posted an article about some ongoing promising immunological research in CLL with the agent CC-122. While much of the recent excitement, for very good reasons, has been about the new class of drugs that block the B-cell receptor such as ibrutinib and idelalisib, or the fresh approval of venetoclax that inhibits BCL-2 leading to programmed cell death, there is still a need for more and Celgene has led the way with a different and important approach, namely drugs that tweak our disrupted immune system such as lenalidomide and now CC-122. You can read my commentary and read about the research that is ongoing here. 

I suspect immune therapies will be needed to seal the deal for many of us. Now that research with lenalidomide in CLL is slowing down, trials with CC-122 may be part of our future.

The full article and the alert with news of some upcoming patient meetings is on the website.

Stay strong.

We are all in this together.

Brian

Biologic and Immune Therapies for CLL (chronic lymphocytic leukemia)

Hi Friends,

This week’s update on the CLL Society website http://cllsociety.org is my unscripted recordings on biologic or immunotherapies.

I start by reviewing my take on the good and bad of the well known and novel antibodies directed against our B cells by targeting its surface marker CD20. These include rituximab (Rituxan), ofatuzumab (Arzerra), and obinituzumab (Gazyva). Among other topics,  I discuss the difference between type I and type II monoclonal antibodies.

I also cover other antibodies, new and old, IMIDS (immune modulating drugs) such as lenalidomide (Revlimid) vaccines, and more.

To listen please, visit the treatment section (found under the Basics tab) of the CLL website by clicking here: http://cllsociety.org/cll-101/treatment/

Please let us know if this helps. I am particularly proud of this recording as it was done live and spontaneously with no notes. I think is ends up being more focused, ironically similar to the drugs discussed.

We plan on bringing more of this type of content. Your feedback on the website or to me by email informs what we add and how we will grow the website. Although there is only myself, my wife (both unpaid) and a wonderful RN, Betsy Dennison as the team, we listen carefully to all comments to help brings what’s needed to best manage our cancer. 

Smart patients get smart care™.

As always, all our content is free and easily accessible to anyone but if you want you may sign up for our weekly alerts to know when we post new content, 1 to 3 x a week, and for our inaugural newsletters which will be amazing. We understand the importance of privacy and don’t share any personal info.

Our website traffic has grown phenomenally in its first 10 weeks. Over a 1000 page views on our busy days. We also hope it will be a launching site for anyone with CLL as we have links to nearly all the quality sites on our front page.

The artwork in the background of the video is again my son, Will Koffman’s tribute to Durer’s Four Horsemen of the Apocalypse.  Will rendered the entire work using only bleach on black cotton.

Nothing much new to report on the personal level with my CLL. Still get tired. Still traveling way too much (over the next 2 weeks I will be in Dallas, Seattle, Las Vegas and Poland to teach and to learn) and still doing too much and getting too sleep. Really it is a bit crazy.

I am waiting on my more granular lab results from OSU. Despite my best intentions, I always worry when I am waiting for my results.

Thanks.

Stay strong.

We are all in this together.

Brian

Volunteer Medical Director, CLL Society Inc.

http://cllsociety.org

BKOFFMANMD@GMAIL.COM

Dr. Wiestner on Novel Therapies for CLL (chronic lymphocytic leukemia), Oral versus IV therapies, Idelalisib plus Chemo-immunotherapy Update and my Lingering Cold

Our very thin CLL Society team is busy preparing for the ASCO (American Society of Clinical Oncology) 2015 Annual meeting which starts at the end of this week in Chicago, but we still found time to bring three diverse and instructive new topics to our website http://cllsociety.org for this week.

Today, Monday, May 25, 2015, we posted Dr. Adrian Wiestner's thoughtful and well-considered interview from ASH (American Society of Hematology) 2014 on what is known and unknown about novel therapies. You can find that here.

Expect more video interviews and commentaries from ASH 2014 over the next several weeks.

On Wednesday, the camera is turned on yours truly for my personal take on CLL topics of interest. We include the short video and an updated transcript on this week's topic of oral versus IV medications. I think you might be surprised at some of the issues and non-issues in what would seem at first glance to be should be a simple choice. I have posted extensively about the tragedies that were associated with potent oral medications before we knew about the risk of tumor lysis with ABT-199 now known as venetoclax or in the case of lenalidomide (Revlimid), where there is also the risk of tumor flare. These risks have largely been mitigated now with new dosing protocols. Please see this prior blog post for part of the story.

 This new section on the CLL Society website using monologues and text will roll out here.

And this will be only the first in a long series of instructional postings on the various CLL therapies.

On Friday, we will post an up to the minute review of and link to an important ASCO 2105 abstract about the latest data on combining idelalisib with chemo-immunotherapy. You will find it here on Friday.

Please let us know what you think, especially about my reading and the transcripts of my monologues. You can contact the CLL Society here or email directly, but the 1^st method is preferable.

We are constantly working to respond to the unmet needs of the CLL community, so we listen carefully to what you write us and try to respond as best we can.

We don't have a big production budget and team or large institutional backing, but we keep going to offer up the most robust and recent, yet still accessible information with no gloss and no agenda other than to inform our community.

Because we believe that SMART PATIENTS GET SMART CARE™

Switching to a personal update, my wife and I are stilling struggling with a lingering upper respiratory infection aka a cold that my beautiful granddaughter shared when visiting from Chicago. No fever or cough for me. With the frequent use of a Neti pot, normal saline and steroid nasal sprays and a single shot of a decongestant (and no antibiotics), I have managed to control the symptoms and survive the pressure changes in the first of several air flights.  Both of us remain “under the weather” after a full week of symptoms, but we are slowly improving.

For most of my immune-competent patients, I would never recommend an antibiotic in such circumstances, but I am not most patients and either are any of my fellow CLLers. We are all immune comprised. Our immune systems are as dysfunctional as hyperactive adolescents who are asked to focus on a single boring multi-step math problem while the rest of the vibrant world pours on around them. Like those teenagers, my immunity’s focus is weak and easily diverted to the wrong target, having lead in the past to my nasty autoimmune problem of ITP.

Tomorrow I am at Ohio State for my three-month follow up on my ibrutinib trial.

Expecting another good lab report. Usually my neutrophils jump up when I am sick at all, even with a viral illness.

I wonder if Dr. Byrd will add an antibiotic and chide me for treating myself, always an ill-advised choice.

Personal confession: I worry about my admittedly relatively mild added illness. Worrying is already too easy to do with CLL, and even more so when we are sick. URIs can lead to chest infections and pneumonia is still the leading cause of mortality in CLL.

I will be much happier when this infection is gone.

I will be home one day this week, long enough to get my every 6 week dose of IVIG.

Late in the week, I will be Orlando for less than 24 hours to lecture on anemia and gout to some 400 primary care providers. Then I fly onto Chicago for the very busy ASCO (American Society of Clinical Oncology) Annual meeting.

Rest is not in the picture. But it is a good busy and I will be with friends everywhere I travel.

I may even get to see the little girl who gave me the cold in Chicago. If we are both well.

Thanks

Stay strong

We are all in this together.

Brian Koffman

Volunteer Medical Director of the CLL Society

Forbes says: "With So Many Terrific New Drugs For Chronic Lymphocytic Leukemia (CLL), Why Worry?" I say it's a Tempest in A Teapot

Hydra (mythical monster that grows two heads when you cut off one)

Elaine Schattner wrote a provocative and helpful editorial in Forbes: With So Many Terrific New Drugs for Chronic Lymphocytic Leukemia, Why worry? I recommend we all read it, but that we also read it critically.

It has to do with her concerns about the dangers of unnecessary treatment.

My friend and fellow cancer advocate Andrew Schorr wisely reminds of us a friend with CLL who has done very well without treatment for nearly 18 years.

We know that about three out of every ten of us diagnosed will follow a very indolent (slow) course and never need treatment.

And so the author cautions us to avoid unneeded therapy. Good counsel. Never take a treatment that's not needed. All drugs and I mean all drugs have side effects. 

Her concern and motive for her editorial is that thousands of us will rise up demanding that our hematologists offer us the new expensive therapies just because they are so darn safe and effective when we would be better off doing nothing, just watching and waiting. Hordes of CLL patients will ignore the carefully tuned 2008 iwCLL guidelines on treatment, and demand an immediate prescription NOW before we are in troubled waters.

I believe it's a false concern. 

A powerful and practical reason that Ms. Schattner is worrying over nothing is that these expensive drug are not yet approved frontline  with the notable exception of ibrutinib in 17p deleted patients as detailed in this recent post). It is highly unlikely our medical insurance is going to pay for an off label use of a pricey therapy when there is ZERO data to support it. And of course, there are vanishingly few of us that could afford the out of pocket cost of at least several thousand dollars per month for any of the new star therapies (in order of appearance on the CLL stage): ofatumumab, obinutuzumab, ibrutinib and idelalisib. And of course, even frontline approval is not the same as approval (and insurance coverage) when there is no indication to treat.

That said, I am sure that there will be a few patients among us who will think it is the height of craziness to sit on our hands. We should strike the cancer while is still in its infancy well before it has the time to achieve its typical mature persistence and wily ways, making it such a formidable foe, making a cure still a dream for almost all of us. Kill it before it grows into a multi headed hydra.  

But a quick review of the facts should dissuade us from this tempting but false path. There is absolutely no evidence that early intervention helps. In this oft quoted article from 1988, Treatment of early chronic lymphocytic leukemia: intermittent chlorambucil versus observation, and this one from the NEJM in the same year show we learned that there was no survival advantage to early intervention. And there are certainly risks. Studies such as these reinforces the importance of knowing the data and also knowing where there is no data.

Wait you say: Chlorambucil may have been state of the art in 1988, but today we have better therapies. Might not the results be different if we looked again using today's drugs? 

Good question. The same sort of trial was set up with FCR, but died on the vine due to lack of enrollment.

That is why trial such as this closed trial on using lenalidomide or this new one using ofatumumab are so important and need our support.

Although prognostic factors such as FISH and ZAP 70 and mutation status tell us much about a group of individuals and little about the individual members of that group, wouldn't we all want to jump out of the high risk frying pan and get far far away from the heat in the kitchen to a calm and cool place of low risk if we could do so by intervening early?

That's is exactly why we need more studies to answer if it is possible to save more lives by using the new mAbs such as ofatumumab and obinutuzumab and the new TKIs such as ibrutinib and idelalisib and others in the pipeline before we traditionally need treatment. There is good reason to believe it just might be so, but without data…. it's only conjecture.

So what do I recommend?

I believe all these drugs should be moved towards more frontline therapy for all patients with the help of well designed trials,  not just those of us with high risk prognostic factors.

I believe these drugs should be studied in those of us with high risk unstable disease BEFORE we need treatment. 

And maybe I am about to sound like a doctor when I say this: I also believe that outside of a clinical trial, there is absolutely no role for these drugs for patients who don't meet criteria for treatment.

The Forbes editorial ends with some sage advice:

“As with other malignancies, the best way to prevent overtreatment is to assure that doctors are current in their education, knowledgeable of “lesser” treatment approaches, and not motivated by financial incentives to give therapy. And for patients, the best prophylaxis is to know that not all conditions carrying a malignant label warrant treatment. Patients might ask, “What’s the least toxic therapy you can give, so that I’m likely to stay alive with the quality of life I want, with this particular form of cancer?”

That's precisely what we are trying to do here. Educate doctors and patients about low toxicity options.

IF YOU WANT A PERSONAL RESPONSE OR TO JUST STAY IN TOUCH, PLEASE SEND YOUR EMAIL ADDRESS TO BKOFFMANMD@GMAIL.COM AS I OTHERWISE DO NOT RECEIVE THEM.

Approval of Imbruvica Frontline for 17p deleted CLL (Chronic Lymphocytic Leukemia) and Important Trials

It's old news (July 28, 2014), but worthy of some reflection that ibrutinib ( PCI-32765 or Imbruvica) was approved frontline in CLL for those of unfortunate enough to have a deletion of the short (petite or p) arm of chromosome 17.

The p53 gene lives on the 17p arm so when it's deleted, there's missing p53. Without functional p53, cancer cells don't die very easily of apoptosis, the programmed death pathway built into all cells that allows them to suicide when they get too old to function, or in the case of our leukemic cells, become increasingly aberrant and dysfunctional. Without  the tumor suppressing p53 gene, the "guardian of the genome", protecting and repairing our DNA and if that fails, then starting to fire up the self destruction pathway, our cancer continues to grow and mutate and get weirder and more aggressive and difficult to treat.

Most chemotherapy works with the help of p53, first damaging the DNA itself, but then needing the p53 to take it from there by recognizing the overwhelming damage and then persuading the injured cell to die. No p53, and we get just the  chemo induced DNA damage, but the cell can live on and even reproduce faulty clones of itself. That is one reason 17p deletion carries such a bad prognosis.

Until we had ibrutinib (and now also idelalisib or Zydelig), our choices for treating 17p deleted CLL were poor- There were and are a few other therapies that do their killing independent of p53 induced cell suicide. Campath works if you don't have any big nodes, but comes with high infection risks. HDMP (high dose methylprednisolone) + R (rituximab) and flavoperidol and even lenalidomide helped some.

No great choices, until now.

I quote from the press release about the trial that lead to the ibrutinib approval:

At baseline, the median age of these patients was 67 years, 58% of whom had at least one tumor  >  5 cm, and 32% of whom had the del 17p mutation. Patients receiving IMBRUVICA demonstrated a statistically significant improvement in progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) as compared to patients treated with ofatumumab. The median PFS and OS has not been reached on the IMBRUVICA arm. There was a 78% statistically significant reduction in the risk of progression or death as assessed by an independent review committee (IRC) according to the modified IWCLL criteria (HR 0.22, 95% CI, 0.15 to 0.32). In addition, the analysis of overall survival demonstrated a 57% statistically significant reduction in the risk of death for patients in the IMBRUVICA arm (HR 0.43; 95 CI, 0.24 to 0.79). This was observed despite a total of 57 patients who were initially randomized to ofatumumab crossing over to receive IMBRUVICA prior to the analysis. For previously treated del 17p CLL patients, there was a 75% reduction in the risk of progression or death as assessed by an IRC (HR 0.25, 95% CI, 0.14 to 0.45).

Ibrutinib seems to do well on all the folks like me with a missing 17p chromosome on our FISH test, and probably even better for the treatment naive 17p deleted patient. Here is another abstract from the NIH on the subject.

This is good news, right now for just those 17p deletion frontline, but I hope it is only the beginning.

I believe these drugs and others in the pipeline need to be available to all appropriate treatment naive patients, not just those with 17p deletion.

It shouldn't be that most of us have to fail chemo first before being offered less toxic options. The ibrutinib data from the earliest trials suggest those who get ibrutinib upfront before any chemo do the best.

That is why there are some really important clinical trials out there to consider for those who will soon be needing their first treatment for their CLL. Here are a few of my favorites.

With ibrutinib or Imbruvica:

Rituximab and Bendamustine Hydrochloride, Rituximab and Ibrutinib, or Ibrutinib Alone in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia

Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

With idelalisib or Zydelig or CAL101: 

A Study of Idelalisib (GS1101, CAL101) + Ofatumumab in Previously Untreated CLL/SLL

A Study of Idelalisib and Rituximab in Elderly Patients With Untreated CLL or SLL

Efficacy and Safety of Idelalisib in Combination With Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia With 17p Deletion (Havasu)

Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab in Subjects With Previously Untreated Chronic Lymphocytic Leukemia

With ABT-199 or GDC-0199:

A Study of GDC-0199 (ABT-199) in Combination With Obinutuzumab in Patients With Chronic Lymphocytic Leukemia

This is by no means a complete list. There are at least 222 trials when you search untreated CLL on Clinicaltrials.gov.

These trials are critical so we can finally prove, as I suspect, that moving these drugs upfront and avoiding chemo all together, is our best course for a long and healthy life.

There are a few other exciting early trials using ROR1 for relapsed disease that Dr. Kipps will be discussing in my next post, an interview from ASCO. ROR1 may prove to be the holy grail of a marker that is truly unique to the CLL cells, making it the perfect target for an anti-cancer drug.

UC-961 (Cirmtuzumab) in Relapsed or Refractory Chronic Lymphocytic Leukemia

This is with a very exciting and very specific antibody developed by Dr. Kipps' team at UCSD. It should be opening very soon.

Autologous ROR1R-CAR-T Cells for Chronic Lymphocytic Leukemia (CLL)

This is from Dr. Wierda's team at MDACC and CLL Global Alliance, building on the promising work out of U. Penn with CART-T cells directed at the much less specific CD19.

Both these are phase 1 trials with all the risks and possible breakthroughs that come with being early to a new therapy. My ibrutinib trial, though later in development, was still a phase 1/2 trial.

There are growing choices out there for those of us facing therapy for the first time, and for those who have relapsed. 

Clinical trials are the only way our knowledge can grow, and the only way these drugs will ever become widely available.

And clinical trials are for many of us, especially in frontline settings, the only path to getting these new agents. 

Speaking of new drugs being available, July 28 was also the date that the FDA gave final approval for Ibrutinib for those who have received one prior therapy. The accelerated conditional approval six months ago had been based on phase 2 data, the final approval looked at the big phase 3 RESONATE trial data.

More from Dr. Kipps on ROR1 soon from our interview at ASCO 2014.

ASCO 2013: Dr. Jeff Sharman on Mantle Cell Lymphoma (MCL) and Coffee and Road Map.

Dr. Sharman is a great educator with a super blog on CLL and NHL (Non-Hodgkin's Lymphoma) talks about MCL.

He points out the specific challenges with MCL and why the changes coming to treatment for other B cell lymphomas such as CLL might be even more helpful in this particular nasty cancer.

While not speaking specifically on CLL, the drugs he discusses should be familiar and his explanations of mechanism of action are both clear and creative- like coffee and road maps.

I will be interviewing Dr. Sharman and many others at iwCLL, a CLL specific conference in Cologne, Germany in a few weeks, so stay tuned. Please let me know if you have any burning questions.

Here is the short ASCO interview:

Again my thanks to the team at Patient Power with whom I worked at ASCO. Andrew Schorr and his team do important work for the CLL and cancer community, and it has been a pleasure to pool our energies and resources.

ASCO 2013: Dr. Sharman on The Biology of CLL being Cracked with a Therapeutic Renaissance Underway

At the ASCO 2013 in Chicago, I had a chance to catch on camera some of the enthusiasm and optimism of Dr. Sharman.

Dr. Sharman is the director of research at Willamette Valley Cancer Institute and medical director of hematology research for The US Oncology Network, and a very creative and visionary doctor and a great blogger. His posts are always worth reading.

In this  interview, he clearly outlines the rationale of using the new small molecules that blocks BCR (b-cell receptor) or Bcl-2 (b-cell lymphoma-2).

He shares some of the development of third generation mAbs (monoclonal antibodies) such as obinutuzumab to turn on the immune system.  We learned in my earlier ASCO post with Dr. Wierda, immunotherapy, namely an allogeneic stem cell transplant is the only proven cure on CLL. And we have strong data from the German trial and others that adding a mAb such as rituximab to FC makes the chemotherapy better, so building a better antibody is an important step forward .

The swelling number of promising new molecules and treatment options needs to be met with an reciprocal swelling number of volunteers for clinical trials to keep the renaissance alive.

Are we already in a therapeutic renaissance for CLL?  I believe we are just in the very earliest stages of the coming change to the treatment paradigm, but we need many more bright lights to guide our way and that will only be produced by the hard work of the bench scientists and the valour of the volunteers  who enroll in well designed and patent friendly clinical research. Only then will we able to say that we have turned the corner on the "dark ages" of CLL

Thanks again to Andrew Schorr and the great team at Patient Power for helping make these interviews possible.

More soon.

More on Halting the Lenalidomide Trial

Please read my immediate prior post on this trial first if you have not already to best understand the context of this post.

I heard from a respected investigator and my person physician in my ibrutinib trial, Dr. John Byrd, involved in the halted trial of Revlimid (lenalidomide) versus Leukeran (chlorambucil) in the elderly with CLL. 

He said the Kaplan Meir curves were narrowing. Deaths are now 28 versus 36, but still with more in the lenalidomide arm. He also said "The cause of death was interspersed among many different causes." And he reiterated "We are very excited about lenalidomide as an immune modulating agent at lower doses" suggesting that we might find use for it at a low dose by not only considering its potential to control the CLL, but also to rebuild our damaged immunity. 

This is completely consistent with the additional information presented below from the well balanced reporting of the Myeloma Beacon News.

I have pasted the last half of their article on the topic, the part that is most pertinent to CLL.

Lessons learned?

1. Don't rush to judgement: Analyze all the data and don't generalize.
2. Don't throw out the baby with the bathwater: Immune modulating drugs may be an important piece in solving the CLL puzzle.
3. Expect the unexpected: Be prepared for something that you are are completely unprepared for.

Here is the last half  on the article. The full  article is available at this link but I jumped to the part that is more focused on CLL

As I said in my prior post, this is an evolving story.

Revlimid Leukemia Trial Halted – No Immediate Impact On Drug’s Use In Myeloma Expected

By Julie Shilane

Published: Jul 19, 2013 4:52 pm

The decision to halt the ORIGIN study was based on an analysis conducted in March that showed CLL pa­tients treated with Revlimid had a 92 percent increased risk of dying compared to those treated with chlor­am­bucil.  Specifically, 16 percent of patients treated with Revlimid had died at that point, compared to 9 percent of patients treated with chlorambucil.

Click on image to view a larger version of it.

The results from the March analysis show that a dif­ference between the overall survival curves started to emerge around 6 months after the start of treatment (see graph on the right).

Celgene told The Beacon that the gap in the sur­viv­al curves has since grown smaller, but has not closed, and that the death rates are currently 18 percent for Revlimid and 13 percent for chlor­am­bucil.  These findings, however, have not yet been reviewed or confirmed by the FDA.

The FDA also has not yet released any information about what factors may have increased the risk of death among Revlimid-treated patients.  A spokes­per­son from the agency told The Beacon, “The FDA is working with [Celgene] to gather the infor­ma­tion needed to better understand the nature of the deaths.”

Greg Geissman, a spokesperson from Celgene, provided some additional information to The Beacon.  He explained that secondary cancers have not contributed to the increased risk of death among patients treated with Revlimid in this study.  He added that secondary cancers were balanced between the two treatment groups, both in terms of the rate of patients developing secondary cancers and the number of deaths at­trib­ut­able to secondary cancers.

Geissman also stated, “As we understand, a preliminary observation shows a greater imbalance in deaths in patients over the age of 80 who have co-morbidities [additional medical conditions]. Our analysis will now look to understand further some of these dynamics and how they may have contributed to the imbalance.”

In addition to analyzing the potential impact of age and co-morbidities on the survival imbalance, Celgene stated that the company will analyze differences in how the patients were cared for at the various centers involved in the study.  The company indicated that the results from these analyses will be presented at an upcoming medical meeting.

The Mayo Clinic’s Dr. Kumar also explained that “Other studies of Revlimid in CLL have shown that these patients can have unique side effects compared to myeloma patients, such as tumor flare.”

A tumor flare reaction is a temporary worsening of symptoms soon after treatment begins.  It can be a sign that treatment is working, but it requires that patients be monitored closely during the first few weeks of treat­ment.

“Given that the [survival] curves start separating out close to a year, it is unlikely that [tumor flare] explains the increased mortality, but it clearly would be one of the aspects to be examined in the future,” explained Dr. Kumar.

“As we know more details about the cause of deaths in the Revlimid arm in the CLL study,” added Dr. Kumar, “we should certainly evaluate if there are specific patients with myeloma where there might be a concern.”

Lenalidomide (Revlimid) Associated with Excess Deaths in the Elderly

Honestly, I didn't see this coming. The IMIDs (immuno-modulating drugs such as lenalidomide or Revlimid) are touted as kinder gentler and safer therapy for the elderly.

Not so says this trial. 

What it found instead in an interim analysis was a significant increase in the number of deaths for those taking lenalidomide compared to those on the old school chemo drug, chlorambucil, an oral alkylating agent.

Now of course the details on the causes of the excessive deaths will help unravel this story, but for now it is a cautionary tale as why we need trials to test what seem to be safe and logical assumptions.

Does this mean if you are in another trial with lenalidomide, you should stop? Absolutely not, but you should discuss with your doctor what this means in your particular circumstance. Probably nothing if you are doing well.

Now this is a newsflash, and the full story is far from told, but since it is a popular non-chemo option out there, I wanted to share this ASAP.

Personally, I still believe there is a role for IMIDs in CLL (too many patients have done well with them), but my bigger belief is that we really have a very primitive understanding of how they work.

We have begun to crack the biology on B cell receptors pathways and BCL-2, but what exactly Revlimid is doing is murky. 

And usually our best results come when we have nailed the underlying basic science. Some drugs have come to us in the past from plain dumb luck, but most of the breakthrough today are based on meticulous pre-clinical basic research.

Here's the news:

GEN News Highlights : Jul 18, 2013

Celgene Halts a Phase III B-Cell CLL Trial Because of Deaths

Celgene today said that after a consultation with the FDA it will stop administering Revlimid® (lenalidomide) in its open-label, Phase III ORIGIN® trial because of patient deaths.

“An imbalance was observed in the number of deaths in patients treated with lenalidomide versus patients treated with chlorambucil,” Celgene said.

The trial, which FDA placed on clinical hold July 12, was intended to evaluate the efficacy and safety of lenalidomide versus chlorambucil as single agent in elderly patients 65 and older with B-cell chronic lymphocytic leukemia (CLL), plus comorbidities that precluded treatment with more aggressive standard chemo-immunotherapies.

The firm noted that, in this particular trial, there were 34 deaths out of 210 patients in the lenalidomide arm compared with 18 deaths out of 211 patients in the chlorambucil group. It added that “all other Celgene-sponsored chronic lymphocytic leukemia clinical trials with lenalidomide are continuing in accordance with their respective protocols.”

Revlimid is approved in the US for the treatment of patients with mantle cell lymphoma whose disease has relapsed or progressed after two prior therapies. The drug is also approved in the US, Canada Switzerland, Australia, and New Zealand, Malaysia, Israel, and “several Latin American countries”—according to Celgene—for the treatment of transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. In Europe, the drug is also approved for the treatment of similar patients with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate. Revlimid is not approved as a CLL treatment.