Good, Bad & Ugly Faces of Campath
Alemtuzumab (Trade name “Campath”) is a powerful monoclonal antibody that has been approved by the FDA for treating CLL patients across the board. There is no doubt that Campath plays an important role in treating CLL patients. For those of you not quite familiar with this monoclonal or want a quick refresher, here is a thumb nail sketch.
Just as Rituxan targets the CD20 marker on B-cells, Campath targets CD52 marker. The big difference is that while CD20 marker is only dimly present on B-cells, CD52 is robustly expressed by all B-cells. Hence, the level of response to Campath is much better in almost all CLL patients. Single agent Campath packs a huge wallop as opposed to Rituxan (which works best in combination with other chemotherapy drugs).
Patients with 17p deletions can thank their lucky stars that Campath is available to this generation of patients. Campath seems to kill cells by a mechanism that is independent of the crucial TP53 gene, the one that resides at the p53 location of your 17th chromosome. Patients with 17p53 deletion are therefore missing the TP53 gene (so-called “suicide gene”). When it is present and working the way it is supposed to work, damaged cells (such as cancer cells damaged by chemotherapy) obediently commit suicide. Deletion of this important gene makes the CLL cells much more able to withstand the damage inflicted by chemotherapy and still not die. The really good news is that there are other pathways of cell kill that do not depend as heavily on the TP53 gene, and Campath is able to use these pathways.
All the above is the good news – now for the not so good and downright ugly aspects of Campath therapy. For starters, infusion related adverse effects (feeling crappy during and right after getting the first one or two infusions) are substantial for Campath. Everything is relative. Rituxan has its share of infusion related side effects, usually brought under control by slowing down the rate at which it is infused into the patient. But Campath infusions are reputed to be quite a bit harder to tolerate. So much so that Campath protocols call for dosage to start small and gradually increases to full strength in a couple of weeks.
Unlike CD20 (the target of Rituxan) which is expressed only on mature B-cells, the CD52 marker targeted by Campath is freely expressed by many different cell types. Among them are B-cells, T-cells and neutrophils. So, when Campath is infused into your body the drug targets all these cell lines and a few more besides. All of them are equally killed by Campath. Bummer! This monoclonal is hardly the tightly targeted and well focused “smart bomb” that one would want.
Now for the truly ugly part. Not only does Campath therapy kill precious T-cells in droves, it takes a long time for T-cell populations to recover. A seminal paper from Karolinska Institute demonstrated that even a year after completion of Campath therapy T-cell populations are a mere shadow of their former selves. It is not quite clear exactly why this is the case. Perhaps it has to do with the fact that Campath lingers in the body for several weeks / months and continues killing T-cells as they try to recover.
T-cells are our main defense against viral infections. Remember, it does not always require an external virus to invade us to get sick. Our bodies retain small trace amounts of many viruses that we have been exposed to over our life times. Good examples are chicken pox virus, Epstein-Barr virus, hepatitis. Reactivation of these dormant traces of viral infections of long ago can cause serious illness when T-cell defenses are down. Chicken pox virus reactivation can cause a painful attack of shingles. Reactivation of EBV can cause all kinds of problems, including possible Richter’s transformation. CMV (cytomegalovirus) reactivation can lead to dangerous bout of pneumonia. Given today’s concerns about a possible swine flu pandemic this fall, increased risk of infection by H1N1 is something to take into consideration before initiating Campath therapy.
Just as important as long standing T-cell deficits is the issue of deep and prolonged neutropenia (low neutrophil counts ) that invariably accompanies Campath therapy. Neutropenic patients are at much higher risk of all sorts of infections, not just viral infections. Many patients suffered life threatening infections in the early days. More recent Campath protocols have built in safeguards to protect patients against infections – more careful monitoring, preventative use of broad spectrum antibiotics and anti-viral drugs, growth factors such as Neupogen / Neulasta to increase neutrophil counts.
FDA has approved use of Campath in CLL with few restrictions, including its use as single agent frontline therapy (based on one of those low powered chlorambucil straw-man comparison studies). Frankly I have my reservations about using Campath as frontline therapy, except in the case of patients with proven 17p and 11q FISH defects – I think its use as frontline therapy for patients with good prognostics might be jumping the gun, using up this valuable bullet right up front when it might be prudent to save it for later rainy day.
Campath Therapy Protocols: Then & Now
We now have more than 10 years of experience using Campath in CLL. The classic schedule is intravenous (iv) infusion of the drug at a dose of 30mg / 3 times a week for 12 weeks. Infusion related side effects as well as life threatening infections seen in early trials have mandated more prudent protocols. This is particularly important when the patient is quite elderly or salvage patient that is severely immune compromised because of prior chemotherapy or aggressive disease.
Earlier work has shown that subcutaneous administration of Campath at lower doses but for longer period may be both effective and easier to tolerate. The aim of the clinical trials we review below was to demonstrate safety and efficacy of less aggressive subcutaneous low dose Campath in refractory CLL patients, especially those with poor prognostic indicators such as 17p deletion, advanced age, fludarabine resistance etc.
Sub-q Campath: German study
Stilgenbauer, Dohner et al of the German CLL group are highly regarded CLL experts. They were the first group identify the value of FISH testing in defining prognostic risk groups. Their classification of FISH risk groups (17p, 11q deletions: high risk; 12 trisomy, “normal”: median risk; 13q deletion: low risk) several years ago stands unchallenged.
Below is the abstract of their very recent paper studying the effect of sub-q Campath in fludarabine refractory CLL patients, with detailed analysis of how different prognostic groups fared. If you want help in getting hold of the full text of their paper, send me a personal email.
J Clin Oncol. 2009 Aug 20;27(24):3994-4001.
Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group.
Stilgenbauer S, Zenz T, Winkler D, Bühler A, Schlenk RF, Groner S, Busch R, Hensel M, Dührsen U, Finke J, Dreger P, Jäger U, Lengfelder E, Hohloch K, Söling U, Schlag R, Kneba M, Hallek M, Döhner H; German Chronic Lymphocytic Leukemia Study Group.
Department of Internal Medicine III, University of Ulm, Ulm, Germany. stephan.stilgenbauer@uniklinik-ulm.de
PURPOSE: The phase II CLL2H trial evaluated safety and efficacy of subcutaneous alemtuzumab in patients with fludarabine-refractory chronic lymphocytic leukemia (CLL). Clinical and biologic markers were evaluated for their impacts on outcome. PATIENTS AND METHODS: One hundred nine patients were enrolled, and 103 received at least one dose of alemtuzumab. After dose escalation, alemtuzumab was administered subcutaneously at 30 mg three times weekly for up to 12 weeks. Response was assessed every 4 weeks during treatment and quarterly thereafter. RESULTS: The overall response rate was 34% (complete response, 4%; partial response, 30%). The median progression-free survival was 7.7 months, and the median overall survival (OS) was 19.1 months. Grades 3 to 4 neutropenia, thrombocytopenia, and anemia occurred in 56%, 57%, and 49% of patients, respectively. Grades 3 to 4 noncytomegalovirus and cytomegalovirus infections occurred in 29% and 8% of patients, respectively. Injection-site skin reactions were generally mild. Efficacy did not vary significantly in subgroups defined by genetic parameters (in particular, in 17p deletion, 11q deletion, mutated TP53, and unmutated VH), but efficacy was inferior in patients with increased beta2-microglobulin (beta2-MG) and thymidine kinase (TK). In multivariate analysis of clinical and biologic variables, age, performance status, beta2-MG, and TK were independent prognostic factors for OS. CONCLUSION: Subcutaneous alemtuzumab appears as effective and safe as intravenous alemtuzumab in fludarabine-refractory CLL. Subcutaneous administration should be the preferred delivery route because of its efficacy, convenience, improved adverse effect profile, and cost savings. In contrast to chemotherapy-based therapy, alemtuzumab treatment overcomes the adverse prognostic impact of VH mutation status, TP53 mutation, and genomic aberrations.
PMID: 19597025
Notice this study used the usual Campath dosage and duration, 30 mg three times weekly for 12 weeks. There was the usual gradual dose escalation in the first week (3mg first time, 10mg the next time and 30mg the third time). Using present day guidelines, patients got antibiotic (cotrimoxazole) and antiviral (famciclovir) prophylaxis, as well as Neulasta (longer acting version of Neupogen, the neutrophil growth factor). The only difference is that Campath was given subcutaneously rather than as an infusion. Patients got the monoclonal as a jab in the arm (or elsewhere), and did not have to sit in the infusion chair with a needle stuck in their veins for any length of time. In this study and elsewhere in similar studies, patients are often able to give themselves the shot of Campath in the privacy and comfort of their own homes.
The patients were all heavily pre-treated prior to entering this trial and fludarabine refractory (defined as getting less than a CR or PR to a fludarabine containing regimen, or disease progression within 6 months after completing therapy). We know by now that this group of patients has poor prognosis and few good therapy options. Below is a summary table describing the patient cohort.
Adverse effects
I was disappointed to see no great decrease in toxicity or adverse effects. Grade 3-4 toxicity is pretty heavy stuff and the table shows significant percentage of the patients suffered this and high grade infections. The sub-q method was somewhat better tolerated than the infusion method immediately after drug administration, but down the road the risk of blood toxicity and infections was roughly the same. Bummer!
Efficacy
So, did the sub-q method work at least as well as the more laborious infusion method of drug administration? Below is a comparison of the results in this study with historical results using the older infusion method. Not much of a difference, certainly not anything we can hang our hats on. I suppose the half full glass viewpoint is that sub-q administration did not reduce the efficacy.
Survival
As we mentioned above, this was a very heavily pre-treated group of patients with poor prognosis, majority of them fludarabine refractory. Below is the overall survival for the group as a whole. Grim news, majority of the patients had relapsed within 6 months and less than half the patients survived past the 2 year mark.
But there was one bit of good news I would like to share with you. Was there a difference in survival rates depending on what the patients did when they relapsed after this Campath trial? You bet!! There is dramatically different overall survival times depending on whether the patients chose a stem cell transplant (blue line) or chose other salvage therapies (gold line), as shown in the diagram below.
Median survival was less than 10 months for patients who chose other salvage therapy options. As for the SCT group, more than half of them are still alive at the time of this analysis. I think you will agree, the SCT folks fared a lot better! The same point was made earlier in an M. D. Anderson study we reviewed, discussing salvage options for patients who have relapsed after FCR therapy. The consensus is now emerging across the board: for poor prognosis patients (refractory to fludarabine, and / or patients who have relapsed soon after FCR or Campath therapies) stem cell transplants are much more effective than any other salvage therapy option available today. Here is the bottom line quote from the authors:
“Although alemtuzumab is efficacious in inducing remissions in fludarabine refractory CLL, the disease will eventually relapseand progress. Currently, the only potentially curative therapy for fludarabine-refractory CLL is alloSCT.”
Some other findings of this study:
- As expected, Campath was equally effective in patients independent of their FISH status. There was no additional penalty paid by patients with the dreaded 17p or 11q deletions.
- Not even IgVH gene mutational status had any effect.
- The only two prognostic indicators that had an impact were beta-2-microglobulin (B2M) and serum thymidine kinase levels.
Low-dose, sub-q Campath in refractory CLL patients
OK, as we have seen above, Campath works just as well (or not, depending on whether you are in an optimistic or pessimistic mood) whether it is given as an intravenous infusion or as a sub-cutaneous jab. The later method of getting the drug into your body may make it easier to take; cheaper too, since you don’t have to rent squatter’s rights for several hours in that fake-leather reclining chair in your oncologist’s back office. But given at the same dosage, sub-q Campath did not have any significant reduction in the hematological toxicity or risk of infections.
But remember the German study was done with the same drug dosages. Which leads us to the next obvious question, what if patients got Campath sub-q, and at significantly lower dosages? Are we over-dosing patients with this potent monoclonal? The abstract below explores this concept. Write to me if you want to read the full text article.
Leukemia. 2009 Jul 30.
Low-dose subcutaneous alemtuzumab in refractory chronic lymphocytic leukaemia (CLL): results of a prospective, single-arm multicentre study.
Cortelezzi A, Pasquini MC, Gardellini A, Gianelli U, Bossi A, Reda G, Sarina B, Musto P, Barcellini W, Neri A, Deliliers GL.
[1] Department of Medical Sciences, University of Milan, Milan, Italy [2] Hematology 1-Bone Marrow Transplantation Unit, IRCCS Foundation ‘Policlinico Mangiagalli and Regina Elena’, Milan, Italy.
Alemtuzumab is active in chronic lymphocytic leukaemia (CLL) patients refractory to alkylators and fludarabine. The aim of this study was to determine the efficacy and safety of subcutaneous alemtuzumab at low dose (10 mg three times per week, for 18 weeks) to 49 patients with pre-treated CLL. The overall response rate was 53%, including 27% of complete responses; it was 42% in patients over 70 years, and 54% in the fludarabine-resistant patients. Forty-five percent of the patients with an unfavourable karyotype responded, including 60% of those with the 17p- aberration. After a median follow-up of 25 months, the median overall time to disease progression was 8 months (responders 12 months, non-responders 4 months). The median overall time to alternative treatment was 9 months (responders 17 months, non-responders 6 months) and median overall survival was 30 months. The treatment was well tolerated: grade IV neutropenia was observed in 17%, and cytomegalovirus (CMV) reactivation in 24% of the patients, with no CMV disease. We observed a total of 30 infections (50% during treatment and 50% during the 12-month follow-up), only one-third of which was severe. This study confirms that low-dose subcutaneous alemtuzumab is effective in poor prognosis CLL, and has a particularly favourable toxicity profile.Leukemia advance online publication, 30 July 2009; doi:10.1038/leu.2009.148.
PMID: 19641526
To cut to the chase, Campath was given at a dose of 10mg, three times per week, for 18 weeks. That is a total of 540mg for the whole enchilada, compared to conventional dosing of 30mg thrice weekly for 12 weeks (1,080mg in total).
It is hard to do a strictly apples to apples comparison between this Italian study and the German study we described earlier in this review, since the patient cohorts were not well matched. I get the sense this group was not quite as far gone as the German study group.
As a result, the overall response rate was higher, at 53%. CR rates were also higher, at 27%. It is interesting to note that while Campath did a good job of clearing out CLL cells in peripheral blood (78%), it was less effective in clearing out bone marrow (63%) and substantially less so in killing CLL cells in the lymph nodes or spleen (53%, 52% respectively). Not surprising results, we knew already that patients with bulky lymph nodes (or grossly enlarged spleen) do not respond so well to Campath therapy.
Bang for the buck, I suppose, in terms of safety and tolerability. This lower dose regimen had less blood toxicity, especially at the grade 3-4 level. Infections were slightly lower as well, but not dramatically so. All in all, if you take slightly better off patients and give them lower doses of sub-q Campath, you will get somewhat better responses and somewhat reduced toxicity profile. We will not have more definitive comparison unless someone does a two arm study with two different dose regimens in well matched patient cohorts.
First dose local reactions were mild to moderate, usually nothing more than redness and slight swelling at the site of the jab. This seems to be the biggest advantage of sub-q method of administration compared to conventional infusion method, the lack of massive adverse response during the very first infusion of the drug. Lower dose and sub-q Campath may be a good choice for elderly patients unable to withstand more robust dosage or risk of infusion related adverse effects. And we must also remember sub-q Campath can be self administered by majority of patients, bringing down cost and hassle factors.
While I hoped for improved efficacy or lower toxicity from these trials, I think you will agree getting at least on-par efficacy and no additional toxicity beats the proverbial kick in the head. As expected, Campath works even in 17p and 11q deleted patients. And once again it is confirmed the best salvage therapy after patients relapse is a stem cell transplant. Intravenous or sub-q, patients should be protected by appropriate antibiotic and anti-viral agents.
13 comments on "Sub-Q and Low Dose Campath"
Very interesting… I had alemtuzumab immediately following my PCR treatment. The results of my treatment seem to be a bit different than reported in the above trials. But then again, as we all know, results are usually more individual with this disease than others.
A little reminder of my flavor of CLL and a bit of history. I was diagnosed with 11q deletions, positive CD38 and ZAP 70, unmutated in October of 2004.
A bout with minimal change disease in July of 2005, and then hemolytic anemia in August of 2006 (Prednisone quickly took care of both of those), considerable growth in my internal lymph nodes, and the fish analysis showing 100% ATM genes(11q22.3), heralded a need for treatment.
So, I received PCR treatment from August to December 28th of 2007. The only adverse effects I had during that period was that I developed a mild cough after the treatments near the end of the procedure.
Immediately following the PCR, in January 2008, with no appreciable reduction in the nodes, and the fish still showing 13% ATM deletion, I was started on sub Q alemtuzumab…30 mg per shot three times a week through March of 2008. Unlike the above study, total injections were only over 9 weeks 3 times a week.
The results. The fish analysis in April of 2008 found NO ATM deletions! YAY! All my lymph nodes also returned to normal over the next 8 months.
The only adverse effects I had was a very light rash and itch for a few hours the day following each injection, did nothing to treat it, my ALC dropped to 0, as expected, but I never had neutropenia and my platelets remained normal.
It has been 18 months (TODAY!) since I completed the alemtuzumab, and not much has changed. Lymph nodes are still normal and I never had neutropenia.
I feel and look normal, except that my ALC seems stuck on 500, and my last CD4 was only 55…so the T-cells are still low.
The only problem I’ve had has surfaced recently…In the last four monthly blood draws, my platelets have started slowly dropping…14 months AFTER the treatment…nowhere near a problem yet, still about 120, but it is consistently going slowly down so we are watching it (during the first week of PCR and also the first week of alemtuzumab, it dropped to 90 but recovered the week after that…no transfusions needed).
In summary, with the majority of the above patients relapsing within six months, I seem to have done quite a bit better than the average did in these studies. Could it have been having the PCR first?
I am taking daily Valtrex and Bactrim but we have stopped the diflucan a year ago, and I have had no infections of any kind…not even a cold. My CMV was negative as well. Have not had a repeat of the anemia or the MCD and feel much better and am more active than I was in the previous 6 years.
I’m not sure why I am boring you with all this information, but although just my experience, I think what I am trying to say here is that the above trials show averages, and not the results that everyone should expect. I feel that my entire experience throughout my battle with CLL has been positive.
If I had read the above information before my treatment, I may have gone in with a slightly negative attitude which may not have helped either. But, I have remained positive…and from what I’ve been told, that’s half the battle, regardless of the drugs or treatments used.
Harley:
You are comparing apples and oranges…
You were PCR treated as frontline, followed by Campath for getting better clearance. Not so these folks. Every single one of them was a refractory basket case, with three or more therapy regimens under their belt that they had flunked. The patient cohorts in both clinical trials were truly salvage cases.
The million dollar question is what happens if and when you relapse after PCR + Campath. Here is to hoping you will have a long and event free remission and you will only have to cross that bridge when you come to it many years hence.
This is a good summary of newer data on the use of Campath. The bottom line is that we continue to circle back to the same conclusion…no therapy to date apart from immunologic attack on the CLL clone results in a satisfactory endpoint for younger patients.
For older patients (especially for those with more than a few comorbidities such as diabetes, coronary artery disease, COPD, etc) the currently available therapies employing combinations of steroids, alkylating agents, purine analogs and monoclonal antibodies make sense because they can “downregulate” the CLL enough to give people a reasonable chance to live out their expected lifespan (we could call this “residual survival”) with a reasonable risk/benefit ratio.
The pursuit of treatment with these types of regimens in younger people (especially in those with poor prognostic markers) without some potential curative therapy as an endpoint needs to be acknowledged for what it is.
I sincerely hope that greater emphasis in the world of research will be placed on pursuing immunologic therapies with potential for cure (such as NK cell therapy, treatments which jazz up an individuals own T cells and/or NK cells or HSCT) as the current chemo-immunotherapies have no curative potential by themselves.
An alternative approach which may prove useful is the search for drugs which potentially could downregulate the CLL clone well enough to convert CLL into a truly chronic disease. This result would be very satisfactory for many of us.
Younger people need to understand that when they begin a protocol such as FCR or PCR (whether part of a clinical trial or not) that they have little likelihood of cure and are best served if HSCT (currently the only realistic choice) is part of their overall plan.
I have personally used a combination of alemtuzumab and rituximab twice in an effort to delay the inevitable road to HSCT. I have been fortunate to have done reasonably well and have “bought” just over two years of time at modest personal cost, but I know full well that I will soon need to move forward toward the “endgame” of more intensive therapy followed by a HSCT.
The experience of others such as your dear late husband has shown us that throwing minor roadblocks up at the CLL clone only leads to progressively unfriendlier CLL down the road. Younger patients who pursue FCR early without a clear plan for their endgame too often end up pursuing one salvage regimen after another until nothing works.
Until we have evidence for a regimen that successfully downregulates the disease into a chronic illness, the only sensible approach for younger people to pursue is to plan to utilize a potentially curative immunologic approach (currently HSCT or possibly NK cell therapy) BEFORE they reach the stage at which only salvage types of therapy make sense. Good luck to all, Rick
Rick, I was clueless when diagnosed 20 years ago, and thus became one of those pursuers of “one salvage regimen after another until nothing works”. The “nothing works” stage came in late 2004. In early 2005 I had a non myeloablative (mini) stem cell transplant as a last resort…. not the most ideal way to go SCT. It was then I discovered Chaya, ACOR, etc., and became “savvy” a little late in the game.
This Campath article is another great Chaya piece. Thanks Chaya! As I’ve posted before (probably too often), I relapsed one year post transplant, but amazinglly my CLL became treatment-responsive again. I just finished my 2nd post-transplant round of SubQ campath. The first post-transplant campath round gave me almost 1 1/2 years. I hope this one I’ve just finished does the same. This round was double the dose described in Chaya’s article. I did 24 weeks three times a week. Both sessions went well save an occasional crash here and there (neuts, whites, reds and platelets) requiring either a transfusion or blood booster shot. I often wonder why I’m so blessed to keep going with a reasonably normal existence, given the extensiveness of my progression, and intensity of my many treatments. I count my blessings and wish the same for you all.
Bob Larkin
Rick:
I agree with you, an “immunologic attack” is something every young patient with progrssive disease should consider as part of their game plans.
“Immunologic attack” is therapy using immune system designed by nature, not man-made drugs; some one else’s immune system since the original equipment of CLL patients has gotten corrupted. It is like getting rid of buggy operting system software on your computer and rebooting with fresh and uncorrupted version from the manufacturer.
A full blown immune system from a matched and willing donor to cure your CLL – that is an allogeneic hematopoietic stem cell transplant and we have written extensively about it. Rick, you also mentions NK cell therapy. I am assuming you are refering to haplo-identical NK cell therapy, where the NK cells are obtained from one of the biological children of the patient. There is a clinical trial that is looking at this very concept; it is half way between a full blown mini-allo transplant and high dose chemotherapy combined with NK-cell kicker to finish off the remaining CLL cells. The big advantage of NK cell therapy is that most people have kids, who automatically qualify as haplo identical donors, while not everyone is lucky enough to have fully matched donors for a mini-allo transplant.
I am proud to say this is a trial that was sponsored and funded by CLL Topics. You can read all about it by going to the original review we did at the time of the launch of the trial, titled “NK cell therapy: Better than a transplant?”
http://clltopics.org/SponsoredProjects/NKCellTherapy.htm As far as I know, they are still recruiting for it. Write to me if you need contact information etc.
Chaya,
I agree with everything that you said above, except that I believe that it may become possible to find a means of “rebooting” one’s intrinsic immune system to teach it to attack and destroy the CLL clone. We are not there yet, so presently the “mini” allo-transplant (with a sibling donor, MUD or cord blood) which I simply referred to as HSCT is the only path likely to work. I did mean using haploidentical NK cells as in Dr. Bachanova’s study when I referred to NK cell therapy, though other approaches utilizing NK cells may be possible. Presently this only makes sense for someone who cannot find even a reasonable cord blood match.
The important thing for younger patients to realize is that courses such as Bob Larkin’s are most likely unless they enter into a plan for utilizing some immunologic attack on their CLL clone soon after undergoing heavy duty chemo-immunotherapy…ie, before the CLL clone becomes more and more resistant, leading to successive courses of ‘salvage’ therapy.
Good luck to all,
Rick
Thanks for the great information.
MJH
Thank you very much for all your good info. I’ll have to admit some of it scares me but only conferms what I already suspected. I just finished 12 weeks of sub-compath and am feeling fine but have to get numerous infusions of platlets and units of blood. The goal is a mini-stem cell transplant in December at Seattle Cancer Care Alliance. Yes.. I am very nerveous but not many choices left. I was diagnosed in 2001. I have no other health issues and am praying for a good outcome.
Thanks again
Chaya
Great info…curious as to the implications of your statement “The million dollar question is what happens if and when you relapse after PCR + Campath”…since we know fcr/pcr eventually lead to relapse does adding campath make this relapse worse?…presently doing consolidation and did not consider that relapsing after using campath might be worse then relapsing after fcr…thanks
romanbob:
I do not know that relapsing after PCR (or FCR) + campath sets up the patient for a worse salvage situation that just PCR (or FCR). Recent work from M. D. Anderson and elsewhere has given us a good look at what to expect in “life after FCR”. How this compares with life after FCR+Campath is anyone’s guess since such studies have not been carried out.
My comment you quote is based on the simple-minded perspective: Campath is one of the most valuable drugs available today to use in refractory CLL patients, event those who have (or have developed through clonal evolution) 17p deletions. Is there a risk in “using up” this bullet? Can Campath be used over and over again without patients becoming resistant to it? Once again, I do not have specific information. But the general pattern seems to be that most drugs become less effective when used a second or third time – compared to first time use.
We are all looking into a murky crystal ball and trying to find the best path forward. No one has definitive answers, certainly where individual patients are concerned.
There are some ongoing studies utilizing Campath “consolidation” after PCR and after FCR. Until the data becomes available one should carefully consider their own anticipated course when they do relapse BEFORE adding the Campath onto either regimen OUTSIDE of a study. I am familiar with 2 individuals who developed serious complications most likely related to the prolonged and deep T cell suppression brought on by the combination and still relapsed fairly quickly. For these 2 people, at least, the risk exceeded the benefit. I don’t believe that either one had been treated as part of a clinical trial.
Whenever the answer is unknown a careful assessment of possible outcomes and a weighing of upside and downside is prudent. Unfulfilled expectations and unwelcome surprises are the worst kind of outcomes emotionally.
Good luck to all,
Rick
Chaya/11qRick
Thanks…while being treated with campath in no calif the decision was based on regular visits to Dr. Kipps who is running a campath consolidation trial that is presently not accepting new patients(tried to get in)…the trial results are due next year…Dr Kipps has wonderful things to say about campath consolidation within certain subsets of patients and recommended this based on my specific situation…much to be learned as the landscape unfolds before us but the advice to have a cll expert on your team who has seen many cll patients and is familiar with likely outcomes based on the “flavor” of an individuals cll cannot be stressed enough…thanks for all the great analysis and thought!!
Romanbob….I presume that you were treated with HDMP+R. The folks at UCSD have been using Campath consolidation a lot in this group, both on and “off” study. I am not personally aware of their overall results, but certainly would not consider disagreeing with an expert such as Dr. Kipps without facts in hand.
Best of luck
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