Dawning of the Age of FCR
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I must confess I was not an early fan of the FCR regimen. I thought it claimed the mantle of “gold standard” far too soon, based on single arm Phase-II clinical trials at a single institution (M. D. Anderson).
But since those early days this powerful chemoimmunotherapy combination of fludarabine (F), cyclophosphamide (C) and Rituxan (R) has been examined at multiple expert centers with hundreds of patients participating in clinical trials in this country and in Europe. While there is small amount of variability in the results obtained from different centers and different patient cohorts (to be expected), there is now clear indication that FCR gets substantially better results than single agent chlorambucil, single agent fludarabine or fludarabine combined with cyclophosphamide. The age of FCR has arrived. The FDA has approved this combination as frontline therapy for CLL. Honor is due: with availability of more robust statistics and multi-center results, I am delighted to change my mind and accept this combination as a valuable and proven therapy option for CLL patients.
Can We Make FCR Work Better?
This is an obvious question and the race is on among expert centers to find the next best thing, an improved version of FCR. Three criteria are important when judging whether or not new combinations are indeed better than FCR:
- Does the new combo yield better response statistics in terms of higher percentage of overall responses, higher percentage of “CR” responses, higher percentage of patients without minimal residual disease even when examined by our most sensitive methods?
- Do the remissions last longer?
- Are the higher response rates and longer remissions obtained without increased level of toxicity?
From patients’ perspective, the second and third item are most important. When rubber meets the road, what we care about is whether the hard won remission lasts a good long time, and whether we can enjoy the remission without a lot of adverse effects that would otherwise spoil our quality of life.
“More Is Better” – But Only Some Times.
Cancer research has long depended upon the concept of attacking the cancer cells from multiple directions. Hitting the malignant cells with multiple drugs targeting different points of vulnerability makes some sense, since it leaves fewer escape routes for the cancer cells. Obviously this approach can go to crazy extremes, more and more drugs added to the alphabet soup. “Non-overlapping toxicity” (meaning that one drug may make you take up residence on the toilet seat while the second one makes you break out in hives and the third tanks your red blood cell count – as an example of non-overlapping toxicity) is a favorite concept with researchers. But I have yet to find patients who feel as comfortable with this view of life.
FCR +L (lumiliximab)
Back in the spring of 2007 I discussed in detail a new monoclonal antibody called lumiliximab that targeted CD23. . Since all CLL cells express CD23 marker, there was reason to hope that addition of “Lumi” to existing combinations would further increase efficacy. An early Phase I clinical trial of Lumi as single agent in relapsed CLL patients showed efficacy without undue toxicity. Building on that encouraging news, a larger Phase I / II clinical trial was initiated where Lumi was added to standard FCR protocol. This time too the patients chosen for the study were relapsed / refractory patients. The latest results from this interesting trial have recently been published in Blood. The abstract is below, as well as this link to the full length article.
Blood. 2009 Oct 20. [Epub ahead of print]
Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia.
Byrd JC, Kipps TJ, Flinn IW, Castro J, Lin TS, Wierda W, Heerema N, Woodworth J, Hughes S, Tangri S, Harris S, Wynne D, Molina A, Leigh B, O’Brien S.
The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States;
Preclinical data demonstrate enhanced antitumor effect when lumiliximab, an anti-CD23 monoclonal antibody, is combined with fludarabine or rituximab. Clinical data from a phase 1 trial with lumiliximab demonstrated an acceptable toxicity profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). We therefore pursued a phase 1/2 dose escalation study of lumiliximab added to fludarabine, cyclophosphamide, and rituximab (FCR) in previously treated CLL patients. Thirty-one patients received either 375 mg/m(2) (n = 3) or 500 mg/m(2) (n = 28) of lumiliximab in combination with FCR for 6 cycles. The toxicity profile was similar to that previously reported for FCR in treatment of relapsed CLL. The overall response rate was 65% with 52% of patients achieving a complete response (CR), which compares favorably with the CR rate previously reported for the FCR regimen alone in relapsed CLL. The estimated median progression-free survival for all responders was 28.7 months. The addition of lumiliximab to FCR therapy is feasible, achieves a high CR rate, and does not appear to enhance toxicity in previously treated patients with CLL. A randomized trial comparing lumiliximab plus FCR with FCR alone is underway to define the benefit of this combination in relapsed CLL. This trial were registered at clinicaltrials.gov as NCT00103558.
PMID: 19843887
This was a single arm clinical trial. Comparison is made to historical statistics for FCR therapy in similar patient cohorts. Three of the 31 patients in the trial got 375mg/m2 of Lumi, in addition to FCR, for 6 cycles. Lumi dose was escalated to 500 mg/m2 for the bulk of the patient cohort (28 patients).
So, did the addition of Lumi make a difference? Is FCRL a better combo than FCR alone? Well, it depends on how you want to spin the results. True, there were higher percentage of overall responses and higher percentage of “CRs”. The adverse effect profile was not significantly different either. But on the important question of response duration, there was no improvement. Bummer! Patients relapsed in just about the same time frame as those who had been treated with just FCR. The rumor mill has it that further development of Lumiliximab in CLL has taken a huge step backward in terms of these ho-hum results. As with all monoclonal antibodies, Lumi is not likely to be a cheap drug and it is hard to make a case for its addition when the remission duration was not any better than just FCR
FCR + Other Chemotherapy Agents
The same issue of Blood where the FCR+L study was published had a very interesting editorial that compared a series of different chemoimmunotherapy combinations against FCR. There is no abstract of this editorial (since it is not very long) but you can read it in full by clicking on the link. I recommend it strongly.
The chart below is from this editorial. Rather than limiting itself to the FCR + L trial reported in the same issue of Blood, the editorial goes further and compares the data for other efforts made in the last few years to “goose” up FCR. Of note, CFAR (which is a combination of FCR + alemtuzumab – also known as “Campath”) and FCR + Mitoxantrone results are also included.
As you can see, the two FCR trials had pretty similar results – within normal variations to be expected in two trials that were not strict back-to-back comparisons.
We had a lot to say about the FCR + Mitoxantrone study both at M. D. Anderson as well as European centers.
Unlike FCR + L where the adverse effect profile did not change significantly from FCR because of adding lumiliximab, addition of mitroxantrone or Campath have substantial effect on adverse effects including cardiac toxicity and hematological toxicity, respectively. Unfortunately, FCR + Campath (“CFAR”) did not give longer remissions than FCR alone. We are still waiting on the remission duration statistics for FCR+ Mitoxantrone. I confess I am not holding my breath on that one, I doubt we will see much longer remission durations with FCR + Mitoxantrone either.
Science moves in slow increments. Negative information is just as valuable, because it allows us to rule out certain things and not waste time bashing our heads against a brick wall that will not budge. I do not want you to lose sight of the fact that but for the brave patient volunteers who participated in these clinical trials, we would not have known that these combinations do not work a whole lot better than FCR. All in all, these results have been disappointing and researchers have to get back to the drawing board to find other ways of improving upon FCR.
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25 comments on "Does addition of Lumiliximab make FCR work better?"
Chaya – do you have any opinion on FR rather than FCR for upfront therapy?
Ron
Chaya, as always, a very good article. I would be interested in seeing FCR-Lite in the comparisons. After two rounds…first was FC and second was FCR, I was switched to the FCR-Lite protocol. I was switched because I responded so well to the first two rounds and my doctor wanted to try and reduce the toxicity. I did achieve CR but unfortunately a year and a half after ending chemo, my immunity levels have yet to rebound and at this point they are unlikely to according to my doctor. (Still, I tend to think of it as a small price to pay in order to gain what is hoped to be a long remission.)
Thank you!
Chaya (sorry for the length of my comments!):
First, of all, once again, thanks so very much for continuing to publish this very worth while web site. It has been invaluable to both my wife and I over the past 4 years.
Is I have previously mentioned in this “open forum”, I was diagnosed with state 4(the Rai staging system) a little over 4 years ago at the age of 56. I was very ill at the time of my diagnosis.
At that time, the local cancer center (UPMC Hillman Cancer Center in Pittsburgh) was involved with a clinical trail/protocol that was entitled “FCR-Lite”. I became an active participant of that study (along with I recall 50+ other participants). I vividly recall that in one of the earlier editions of “CLL Topics” (several years ago) you wrote about the FCR-Lite protocol. In fact, in one of your editions you included a “story” about one of my fellow participants in the FCR-Lite study – entitled “Forest Bump”!
As we are all aware, with any protocol, there are both positives/pros and negatives/cons.
For me, the positives/pro are that:
1. Fortunately I achieved a complete response/complete remission (CR) by the end of the initial 6 month comprehensive treatment plan.
2. Fortunately, 3 ½ years later (as of today), I am thankfully still cancer free.
For me, the negatives/cons are that:
1. I am one of the “few” patients who developed a highly allergic reaction to the “R” (Rituxan) treatment, which was going to be continued to be administered to me on a quarterly basis for 2 years following the initial 6 month intensive FCR treatment. My reactions included severe flu likes symptoms and I also became neutropenic (and needed to be hospitalized). Thus, my ongoing Rituxan treatments were discontinued – after my oncologist consulted with Dr. Rai.
2. As a result of the toxicity of the chemo (the F & C) and even though it was “Lite”, my immune system became severely suppressed (IGG, IGA, IGM levels). As a result, for the past 3 ½ to 4 years, I have been (and continue to receive) routine IVIG treatments every 4 to 6 weeks. These treatments temporarily “boost” my Igg levels, but as you are aware, the IVIG treatment does nothing for either: my Iga and/or Igm levels (which continue to be severely depressed). As a result, I am prone to various infections – respiratory, upper respiratory and other types.
3. Unfortunately, I am one of the “few” patients who also developed a highly allergic to the IVIG treatments (flu like symptoms, rashes, red/irritated eyes, headaches, etc). As a result, with each IVIG treatment I receive IV benedryl and steroids. I am also on a taper dose of steroids for 7 days following each treatment.
For me, 4 years after my initial diagnosis and 3 ½ years after the end of FCR-Lite treatment, the FCR-Lite protocol seems to have been extremely effective – (despite the “cons” which I previously listed.
So, after this long dissertation about my personal journey, my questions/inquiries to you are as follows: what has become of the FCR-Lite study/protocol? If the FCR-Lite protocol was effective (which by my personal experience I believe that it was!), why did it not become “popular/main stream”? Why has the FCR-Lite protocol/treatment essentially disappeared from the literature? Why is the FCR-Lite protocol not mentioned in the recent edition of your publication?
As always, thanks so very much for the timely information and insight that you share with all of us – I very much appreciate it.
Pittsburgh, PA
Two questions:
1. Are Fludarabine, cyclophosphamid, or Rituxan CLL cell specific?
2. Is there definitive evidence that FCR appreciably increases O.S. for untreated patients?
For me the question isn’t, whether a new drug combination is better that FCR, but whether it is better than FC. As I am allergic for Rituxmab.
Thanks Chaya – as you say its valuable to know what DOESNT work as well as what does. It would be interesting, some time, to be able to compare Azzera (Humax CD20?) regimes with FCR so as to get a picture in one’s mind what to ask about when one does have a relapse.
Lawrence
(20 months in remission after an early and successful UK FCR treatment)
Chaya, are you aware of any responders to a second round with FCR? I had a good two year remission from FCR with Michael Keating prior to my ’05 stem cell transplant. I have since relapsed, but have managed well with campath twice. I’ll be looking for the next thing in a year or so, I’m sure ….and, wondering if a 2nd round with FCR should be on my list? Gee, I remember at diagnosis in 1989 there was only one protocol, chlorambucil (lukeran).
Bob Larkin
mschwalm48:
Rituxan is CD20 targeting monoclonal and therefore specific to mature B-cells (not just CLL cells, all mature B-cells). Cyclophosphamide and fludarabine are old fashioned chemotherapy drugs and not targeted to just CLL cells or even just B-cells.
The scenario is a CLL patient that is in need of therapy because the disease has gotten to the point (B-symptoms etc) where Watch & Wait is no longer possible. In this situation, results of the recent and very well conducted German trial say patients treated with FCR have longer survival than those treated with F, F+C or chlorambucil. Frankly, in my opinion once the patient has onset of B-symptoms it is no longer an option not to treat. Quality of life takes a huge hit at that stage of the disease. Frequent infections (one of the B-symptoms) can cause both morbidity and mortality. Most CLL patients eventually die of infections – pulmonary infections in particular.
Feike:
My husband too was hypersensitive to Rituxan. Hence his therapy was FC + ofatumumab. Ofatumumab is the new fully humanized anti CD-20 monoclonal antibody that has won FDA approval. Since it is fully humanized as opposed to partially murine (mouse)protein based Rituxan, people who are allergic to Rituxan can use ofatumumab. We have a lot of information on ofatumumab (Arzerra, Humax-CD20) on this site as well as http://www.clltopics.org
bolark:
Please read the article “Life after FCR” where patients who had relapsed after an earlier FCR remission were treated with a variety of salvage therapies, including a second round of FCR.
I will move FCR-Lite up to the front of my to-do list.
Like Chaya, I was suspicious of FCR when it was just based on the MD Anderson’s phase 2 trials, but now that the German CLL8 trial has confirmed that it has a high response rate and long remissions, but in addition gives a longer overall survival than FC, it is the current gold standard. Can it be made better? One of the problems with this is how long controlled trials will take to give us an answer on that. In the UK we are comparing FCR with FCM-R, but a trial that takes 6 years to demonstrate an overall survival benefit is not attractive. That is why we need trials that give an earlier answer.
It looks like the clearance of minimal residual disease is the surrogate that will do the job. If FR or FCR lite can produce this end point then there is no need to do more, but if they can’t then full dose FCR should be next and mitoxantrone might be added if it is still not achieved. Other drugs that might be added to achieve MRD negativity might be Campath or Revlimid.
Of course there are still some patients (older or with co-morbidities or only slowly progressive disease) where achieveing MRD negativity might not be necessary.
rekarp:
FCR was pioneered at M. D. Anderson and FR was championed by Ohio State University. There is certain amount of not-invented-here syndrome when it comes to which combination is favored by experts at the two centers.
In light of that, it is particularly interesting that recently I read Dr. John Byrd of OSU has suggested FCR might be a better choice for some patients, especially those with 11q deletions. I am not quite sure where I read it, perhaps Dr. Hamblin can chime in.
There is no question that cyclophosphamide adds its particular component of toxicity. But if FCR gets deeper and longer lasting remisisons by adding this third component – especially in difficult to treat Bucket C patietns – then once again we are forced to weigh the risks and rewards. The problem is that it is very hard to quantify either the risks or the rewards, so we are making decisions based on dimly understood issues.
This is just my two cents: if the patient is relatively young and healthy, has 11q deletion, I would opt for the potentially higher impact of FCR. In older patients or those with more fragile overall health, I would instead focus on the possibility of reduced adverse effects and go with FR. Younger and healthier patients are better able to handle the risks and getting a deep remission is more important in their case. We discussed some of these issues in a recent article “Does Age at Diagnosis Matter?”
I’m almost 3 years into what appears to be an MRD neg CR from only 4 cycles of FCR with slightly reduced F.
I can’t help but wonder if the fact that I got significantly less of the stuff in my frontline therapy means that I can reasonably hope for better results with FCR if used as salvage treatment.
Bob
Finished the full FCR treatment at Mayo 4 months ago. In CR now. Have a resulting problem of stomach lesion that we are looking into now.
Getting through the FCR for the 6 month treatment was difficult but not of a high severity. I continued to walk 2 miles for at least 4 days a week. But had to stop later on in my treatments during the week I received the FCR. HIgh expectations that will remain in CR for years to come. From my results and going thru FCR,I support increased treatment CLL patients needing chemo.
Chaya and Dr. Hamblin:
Any thoughts/insights/updates/perspectives that you have re: FCR-Lite would be greatly appreciated.
Chaya, thank you so much for keeping us inform.
Stay well,
Monique
Chaya,
I was initially treated at OSU by Dr. Byrd in the last week of July 2009. At that time Dr. Byrd reiterated his preference for using Rituxan and Fludara concurrently except for 11q where he thought that the addition of Cyclophosphamide would be of benefit. Interestingly, when I consulted with Dr. Kanti Rai in June of ’09 he was of the very strong opinion that Dr. Byrd’s view of with holding Cyclophosphamide was incorrect and strongly advised me to go with FCR. In May of ’09 Dr. Adrian Wiestner of NIH was of the opinion that in my case (I am a 13q and was very bulky with high WBC near 300k) FCR “might not be the best choice for me” and favored The RF concurrent protocol.
In hindsight I wonder what effect the added burden of Cytoxin would have had on my kidneys if I had gone with FCR given the kidney failure I suffered after round 2 in Rochester NY? We are dealt the hand and play the cards the best we can in this most imperfect of life’s games.
I detect an unusual area of neglect in your exploration of this subject. I am a little frustrated at the rush to add yet more toxic elements to the existing protocols without an exploration into how some of the existing agents could be used more effectively in reduced dosages or given in different timing sequences perhaps based on subtypes of patients selected for factors of age, comorbidities, degree of aneuploidy and robustness of immune system for starters.
While I am hardly qualified to judge the merits of Byron’s recent comments on the strategy of changing the infusion medium from saline to 5%dextrose in hopes that the higher metabolic activity in the lymphnodes would increase the uptake of the chemo given with sugar and thus its killing power, I like the kind of thinking which that strategy exemplifies. If the right sugar and bonding to the right therapy agent could be accomplished it might work but it might only work for bulky CLL or SLL patients.
Without saying whether this idea is even feasible it is a useful example of another problem of who would fund this type of approach? A new sexy CD20 tweaked mAb will bring in big bucks for Big Pharma whereas dextrose or some other sugar will not make anybody rich and may even result in reducing the quantities of existing agents.
Much progress was made with pediatric ALL over the time period from the early 1970s until 2008 with out adding any new agents but tinkering with usage of existing drugs. My source for this info was the Mayo Clinic Chicago Symposium in 2008 and a talk by Dr. Tallman.
Great subject needing expansion and constant attention in the explosion of new agents and increasingly complex protocols.
WWW
Chaya –
With all the interesting talk above:
1- Are there any FR vs FCR studies Pending to solve that dispute?
2 – Any FCR vs FCR Arzerra studies pending?
3 – The 11q status pushing full FCR seems reasonable, and the 17p folk have a hard road to hoe, but what about us trisomy 12 middle-roaders. Much talk has gone back and forth about increased/no increased risk; and the salient difference I can find so far (even with / especially with FCR) is that our remissions are shorter than 13’s and 11’s but longer than 17’s.
Many good questions in the discussion section, but unfortunately there are few cut and dry answers. I doubt a head to head FR versus FCR trial will be done. But comparing single arm FR versus single arm FCR clinical trial results gets us part way there. We are more likely to see double arm FCR versus FC+Arzerra cliinical trial results since the new monoclonal needs to earn its reputation.
No one would scoff at a lower risk protocol that still gives high responses and long remissions. But I doubt using dextrose as the infusion medium will do it. One patient story does not make for solid science. Yes, pharmaceutical companies would like to make money, they are not non-profit organizations. Nothing wrong with that per se, our system of capitalism is terrible – except for the fact it is better than all the rest out there. But do you honestly think there are no honorable or caring CLL researchers out there who would explore a viable option for patients if it was that simple? I am not that cynical. I am the first one to tell people to judge risks versus rewards before making therapy choices. And it is very frustrating given the murky nature of our crystal balls. But when the frustration gives way to illogical conspiracy worries then we do not serve ourselves well.
12 Trisomy is a tough nut to classify. On the one hand it does not often cause the fast paced proliferation of CLL cells 11q and 17p deletions cause. On the other hand, it does lead to bulky adenopathy which is tough to treat. I do not know of any quick answers to the question of what is best for patients with 12 trisomy. These patients should be examined and evaluated on an individual basis and therapy decisions made accordingly. I would agree that there is less research on 12 trisomy than there is on 11q and 17p abnormalities.
By all means if there are articles out there that shed light on the areas I have left unexamined, please bring them to our attention. I do not claim to be all knowing. But having been around the CLL block more times than I care to remember, this much I have learned. One-of-a-kind miracle cures and anecdotal stories do not make for credible research or good science. Credible medical research takes time, patience and lots of hard work on the part of dedicated researchers and brave volunteers participating in clinical trials. There are few short cuts that don’t end up doing more harm than good. Cancer patients are needy folks and the frustration makes us wish there were simple solutions to what ails us, easy answers to the tough questions.
If I find any good therapy solutions that do not have matching toxicity I will be more than happy to write about them. As a scientist I am always ready to change my mind, but I will not advocate unproven theories or wishful thinking. But I do understand and accept my way of thinking is not everyone’s cup of tea. We are all adults here; each and every one of us has both the right and the responsibility to make our own decisions. There is no question that articles on Updates are colored by my own perspective. Fortunately, there are many voices out there and you can decide which ones make most sense to you
Tom was on the FCR trial for front-line treatment in 2004. He did hit an npr, but never got that golden MRD negative. Relapse took around 3 years, but the interim was one of major side effects that slowly went away. Vomiting was one of the worse and this was while he was in remission. But—-his QOL after FCR was the best—before his dx, he was so sick all the time. I know that Dr. Keating says there are still patient’s in CR from this trial in 2004. I think one has to look at the marker’s. Tom is unmutated using the VH3.21 gene. Research is showing this gene to be more negative than positive as far as treatment is concerned. He is also Zap70+ and CD38+. (interesting that he was CD38- until after FCR).
Tom is one of the highly “allergic” patient’s to treatment. Revlimid was very scary for him. Rituxan gave him a bad cough for days after infusion. Now, he is on Azerra, and is the second patient of Dr Keating’s to have neuropathy in his fingers and lips from Azerra. This is a new finding on side effects of Azerra. Both patient’s also have problems with numbness when exposed to cold temperatures. Some connection, perhaps?
FCR was not a walk in the park, but overall, it was quicker and not as intolerable for Tom as Revlimid.
Dear Chaya, Your comments please on the side effects JIOU reports. Has the manufacturer responded? I’m wondering if it is the combination, doseage,etc.rather than the Humax-20? Blessings to you and your tireless work on our behalf, Stan Wencley
stan wencley:
Which manufacturer? FCR is a combination of three drugs, so the adverse effect profile is a combination of the effect of all three drugs. If you are talking of Arzerra + Revlimid, each of these drugs has a long list of adverse effects, especially Revlimid. You must also remember Tom has had a lot of other chemotherapy regimens before this latest Arzerra + Revlimid combination. His response (and adverse effects) will be determined by not just what he is getting right now but all the things that have gone before as well.
Arzerra (ofatumumab, Humax-CD20) + Revlimid (lenalidomide) is a potent but relatively new combination. We will no doubt learn more about this and other combinations as time goes on. The neuropathy due to Arzerra is a new one to me. I would have thought it more likely to be due to Revlimid. I do not remember seeing any neuropathy issues in the single agent Arzerra study. I could be wrong, I will double check and let you guys know if I find anything worth reporting on that front.
Dear Chaya,
Have you seen this from Dr Hamblin blog regarding treatment of
Trisomy 12 Wednesday, April 09, 2008
“In advice that I have been giving over the past 5 years I have been stressing that CD20 is brighter in patients who have trisomy 12. Indeed we noticed some time ago that trisomy 12 CLL was rather different from other types of CLL [1]. Today, published in the British journal of Haematology comes mathematical confirmation of our observation, from Michael Keating’s group [2].
In patients with trisomy 12 there were 23,603 CD20 antigenic sites per cell compared with 10,781 for del 13q, 9,341 for del 17p, 8,828 for those with negative FISH and 5,886 for those with del 11q. The figures for trisomy 12 and del 11q patients were statistically significantly different.
Does this matter? Yes, because rituximab targets CD20. In the same paper the MDACC group report that the combination of rituximab and GM-CSF produced responses in93% of patients with trisomy 12, 73% in patients with negative FISH, del 13q or del 17p, and 50% in patients with del 11q.”
Have you experienced Rituxan a good choice for Trisomy 12 for this
reason?
Thanks for everything always.
Jean
Jean:
Interesting comment from Dr. Hamblin’s blog.
I have not “seen” enough 12 Trsomy cases in my anecdotal database to add to this interesting observation. As for use of Rituxan, I think it is now safe to say that ALL patients benefit by the addition of Rituxan (or its new sibling Arzerra) to standard chemotherapy. I think there is little doubt left that Rituxan + FC works a whole lot better than just FC alone, and the same goes for F+ R verusus just F. I have not seen sufficiently robust statistics to confirm that addition of Rituxan to FC makes a particularly significant difference in the case of 12 Trisomy, over and beyond the impact it has in patients with other chromosomal abnormalities. Nevertheless, it is one more good reason why Rituxan should be added to FC when treating 12 trisomy patients.
Trisomy 12 is often accompanied by bulky lymphadenopathy – in that sense it is similar to 11q deletion. I doubt single agent Rituxan is potent enough to clear bulky lymph nodes, whether or not the cause of the adenopathy is 12 trisomy. Just my two cents.
Chaya-
According to Michael Keating, neuropathy was not reported in the first trial of Azerra. I could be wrong, but I thought he said that it was “overlooked”. He said that he was now documenting it through MDAnderson. So, I am not sure. Tom also had neuropathy with Revlimid, but only his lips. Azerra has affected his fingers and lips again. Could it be rituximab? Maybe……but Tom has had a few years of Rituximab treatment and the only time neuropathy occurred was when it was combined with something other than solumedrol. (Revlimid and azerra).
jlou
Chaya, I was diagnosed with cll in 2005, and in 2009, after my WBC climbed to 161 I required treatment. At age 74 I made an appointment with Dr Michael Keating, MD Anderson, and volunteered for his FCR clinical trial of untreated cll patients. Treatment was not a piece of cake. There were 6 cycles, and after each cycle, I could barely get out of bed.
After chemo completion, in Dec 2009, I developed 3 different infections – an ichy bacterial skin rash, sinus infection, and bronchitis, all of which required antibiotics. My WBC in Mar, 2010. was 1.2, which means my immune system is almost nil. Usually, how long does it take to get back a normal WBC, between 4-10? Also, I still have shortness of breath and tire easily. Will these side effects soon disappear? I am eager to resume my gym membership.
The Lumixilimab phase 2 trial ended I think in June of this year. A report on the results was supposed to be release this month. Any sign of it?
With less chance of allergic reaction and much more CR are the results of the phase 1 trial not at least somewhat encouraging, even if remission duration is not longer than FCR? Is there not also hope for L alone as maintenance after CR, since it is less damaging to the immune system? And a potential for L alone as a front line treatment…again since it does little damage to good B cells…so the cost is mostly dollars, not patient safety?
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