Follow the Money Trail
An interesting report in the recent ASH2009 conference dealt with the cost of taking care of patients after they had completed Campath therapy. Even if you have gold plated insurance coverage and your carrier pays all your medical bills without a single protest, this paper is still important because it highlights the real life implications of the possible adverse effects that are associated with Campath. Notice one of the authors is an industry representative from GlaxoSmithCline. What makes it interesting is that GSK does not own rights to Campath, that privilege belongs to Genzyme.
Costs to Medicare of Treating Chronic Lymphocytic Leukemia Patients with Alemtuzumab
Marie-Hélène Lafeuille, MA1*, Francis Vekeman, MA1*, Matthew Kerrigan, PhD2*, Si-Tien Wang3* and Mei Duh, MPH, ScD3
1Groupe d’analyse, Ltée, Montréal, QC, Canada
2US Health Outcomes, GlaxoSmithKline, Philadelphia, PA
3Analysis Group, Inc., Boston, MA
Background: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world, comprising over one-third of all new leukemia cases. Alemtuzumab is a humanized monoclonal antibody targeted to lymphocytes through the CD52 receptor that has been demonstrated to reduce the amount of malignant lymphocytes in patients with CLL. Alemtuzumab is, however, associated with various adverse events (AEs) including cytopenia, infections, and cardiac dysfunction. The current study aimed to quantify the incremental cost to Medicare of treating CLL patients with alemtuzumab.
Methods: An analysis of patients’ electronic health insurance claims records (1999-2007) from the Medicare 5% national sample was conducted. Patients with continuous enrollment for 3 or more months prior to their first observed claim with a CLL diagnosis, no more than two malignancies (by ICD-9 diagnostic codes associated with claims), and 1 or more claim for alemtuzumab were included in the analysis. Patients who had HMO coverage under Medicare were excluded from the analysis to ensure data completeness. A pre-post design was used to quantify the incremental costs associated with alemtuzumab by calculating health care costs within 6 months after alemtuzumab initiation relative to the 6-month period before alemtuzumab initiation. Mean monthly (per-patient per-month, PPPM) costs were calculated and were grouped by sites of care, service type, tests and procedures, treatment and drugs, and by AEs. To estimate the costs of AEs, claims with ICD-9 diagnostic codes for the AE of interest were grouped and mean PPPM costs were calculated for those groups. These groups were not mutually exclusive: claims could be associated with more than one diagnostic code. Statistical comparisons between the pre- and post-treatment periods were based on paired Student t-tests.
Results: A total of81 CLL patients treated with alemtuzumab formed the study population. The mean age (SD) was 75.2 (7.5) years and females represented 38.3% of the cohort. Patients were observed for an average of 50 months and mean time between the first observed CLL diagnosis and initiation of alemtuzumab treatment was 36 months. After alemtuzumab initiation, mean total healthcare costs increased from $4,272 to $10,385 PPPM (cost difference: $6,113, P<0.0001). Patients had a mean of 11.8 claims for alemtuzumab and the mean cost (SD) for alemtuzumab was $4,006 ($3,277) PPPM in the post-alemtuzumab period or 39% of total costs. Costs associated with diagnostic codes for cytopenia were $1,658 pre-alemtuzumab compared with $4,114 post-alemtuzumab (P<0.0001). In the pre- alemtuzumab period, costs with infection-related diagnostic codes were $107 PPPM compared with $841 in the post-alemtuzumab period (P=0.0005). Costs associated with cardiac dysfunction diagnostic codes were $766 PPPM in the pre-alemtuzumab period and $1,692 in the post-alemtuzumab period (P=0.0172) (Table 1). Note that these cost categories are not mutually exclusive.
Conclusions: Amongst a cohort of Medicare fee-for-service patients with CLL, alemtuzumab was associated with a significant increase in healthcare costs in the 6 months after initiation of therapy of which the costs of alemtuzumab, oncology services, cytopenias, infections, and cardiac dysfunctions were large components.
Editorial
Below is the table from the abstract, cleaned up a bit for easy reading.
The chart lists the average monthly cost per patient. I have highlighted in red the cost differences that are statistically significant. The total cost of taking care of patients before and after Campath therapy is broken down into three major categories.
- The first one is cytopenias. We know by now that Campath can cause significant drop in the counts of all the other cell lines besides the CLL cells we want to see get killed! Anemia, neutropenia and thrombocytopenia (drops in red blood cells, neutrophils and platelets respectively) are common and it costs money to take care of the fallout from these issues. Think of growth factors such as Procrit, Neupogen, possible transfusions in refractory cases. None of this stuff is cheap.
- The second category is infections. Frankly I am surprised the difference is as small as this report suggests. Anecdotal stories are dime a dozen but based on what I have heard from patients I would have thought the difference would be higher because of potential for hospitalizations after Campath therapy. Viral reactivations are a well known risk factor for this powerful drug. This relatively small difference suggests we are getting better at protecting patients with prophylactic medications against bacterial and viral infections and that is good news indeed.
- The last category is bit of a surprise. Did you know Campath therapy increased the cost of taking care of post treatment heart disease?
Who knew heart disease is yet another risk factor of Campath therapy? I wonder if they screen patients for their general cardiac health prior to approving them for Campath therapy. If you are a patient that has been through Campath therapy, do comment and let us know if your physicians asked about your cardiac health history prior to treating you with this monoclonal antibody. Studies such as this are useful because they highlight the real cost of therapy. As you and I know, the story does not end once the nurse has removed the infusion needle from your arm and tells you to go home. We keep paying for months after, both in terms of medical co-pays and health issues that linger.
Cost of health-care is much in the news. Tempers flare and peoples’ perspectives are often colored by their political persuasion. I try hard to report on this and other interesting studies without so much as dipping my toes in the murky waters of partisan politics. CLL is a non-discriminatory cancer. People of all political stripes are stricken by this disease and our support goes to each and everyone of them. I hope you feel the same way and your comments reflect that solidarity with your fellow CLL patients.
25 comments on "Cost of Therapy: Follow the Money Trail"
Do we ever get good news?
There was good news in this abstract and I commented upon it. As researchers learned more about viral reactivations and infections risk associated with Campath therapy, the best practices they developed seem to be working, reducing the cost of taking care of post therapy infections.
I was recently out in Ohio and was told that the “C” in FCR has been linked to secondary cancers. So the latest thinking at the Ohio State CLL center would essentially be to avoid any chemical that starts with a “C”.
Chaya,
In my opinion, this study is of little value. No reference points are used to compare the costs of healthcare following any other therapy such as, for example, FCR. How are we to know whether those costs in a similar group of patients receiving different chemotherapy exceed those documented in this group?
It also seems inappropriate to compare health costs of patients during the months PRIOR to therapy with the costs in the months following therapy. It seems axiomatic that the reason that the patients received therapy is because there disease was getting worse, so one would expect greater healthcare costs at that point in time.
These were older patients and I suspect that their healthcare costs following ANY therapy would be greater than would those of a younger cohort of patients.
As to the issue of cardiac toxicity, no documentation is given. Older people with underlying cardiac disease are more likely to have difficulty when their bodies are stressed by any therapy, especially if they have underlying anemia and especially if their anemia worsens (even transiently) during therapy.
As to the issue of alemtuzumab related cardiac toxicity…this was raised in 2 groups of patients: patients with mycosis fungoides/sezary syndrome and patients who received alemtuzumab during the course of HSCT. Careful review of the patient’s records revealed a likely association with prior or coincident anthracycline (doxorubuicin) use which is recognized to be associated with cardiotoxicity. It is very questionable whether or not alemtuzumab directly plays a role in cardiotoxicity.
Some therapies (back surgery, for example) may be associated with decreased healthcare costs in the months following surgery when compared (in the same patients) to the months preceding the therapy, but others (chemotherapy) which may be associated with side effects of variable duration inevitably cause more healthcare costs on average in the period during/after treatment than in the period before treatment when the patient was in “better shape”.
Such a study backed by one pharmaceutical group raising questions about another’s drugs smacks of the type of mudslinging usually reserved for the political arena!
warmac9999:
I have the greatest respect for John Byrd and the rest of the CLL team at Ohio State. But I would take the advice to avoid cyclophosphamide (the “C” in FCR) at any cost – with a pinch of salt.
FCR was “invented” at M. D. Anderson. Ohio State group pioneered FR, dropping the “C” from the MDA combo. Both are very potent chemoimmunotherapy combinations. FCR has been shown to give higher remission rates, especially in patients with high risk FISH deletions such as 11q (ATM) deletion.
As for causing cancer, I fully agree cyclophosphamide is mutagenic, capable of causing secondary cancers. For that matter, the same can be said of fludarabine as well, the “F” in the Ohio State combination of FR.
I have long ago realized researchers are also human beings, they too suffer from the human frailty of “not-invented-here syndrome”. By the way, I believe Dr. Byrd is on record recommending FCR over FR for 11q deleted patients.
I’m only two years into CLL and have received excellent analysis and care through the USA Veterans Administration. We’ll see how “golden” it is in the future.
I know many veterans fail to sign up and use this great service. Readers, if you are a veteran please check your options.
Thank you USA taxpayers for providing for my health care.
This is interesting. The question now is, how do other therapies impact the cost of care before and after treatment. Does FCR, FR, HDMP+R or others result in lesser increases in cost of care.
Keep up the useful work,
Dan
Rick:
You make the point:
“It also seems inappropriate to compare health costs of patients during the months PRIOR to therapy with the costs in the months following therapy. It seems axiomatic that the reason that the patients received therapy is because there disease was getting worse, so one would expect greater healthcare costs at that point in time.”
This study was done following the SAME group of patients before and after Campath therapy. I agree with you, these guys prior to therapy would have been sicker and therefore cost more money to care for. The results are exactly the opposite. Since one can hope their CLL is under control after therapy, the additional cost of healthcare is reasonably attributable to post therapy adverse effects.
In fact, since the same group of patients were evaluated before and after, many of your other arguments are also moot.
Would FCR cause greater costs after therapy? I do not know, that information has not been published. Given that Campath has been approved for frontline treatment of CLL, the only monoclonal antibody that has been given this coveted status, it is reasonable to ask about the costs involved.
I think there are a couple of take home points that are of some value in this study. One, that the costs of post therapy infections are lower than one would have expected, suggesting effective prophylactic protection is being followed in majority of cases. Second, the higher than expected (at least, higher than I expected) increase in cardiac disease. Once again, it is the same group of patients followed before and after therapy and it seems reasonable to me that any change is attributable to Campath and not some other factor.
Yes, there is possibility of company rivalry in this report, which is why I took care to point out that one of the authors was from GSK, and they do not own rights to Campath.
Seems like always a double edge sword.
I had been diagnosed with CLL in 1999. I was slotted into a high-risk group in early 2005. One treatment option offered was Campath and Rituximab, which I subsequently followed. Yes, my Drs. included cardiac investigations in their pre treatment exams. Feb. 2006 I was diagnosed with ITP which was treated with RCVP. The treatment also was very effective for CLL. At the time, I did raise the question, “Was the ITP caused by my use of Campath.” They could not say for sure other than it is a possibility.
I am now in my 5th cycle of treatment with RCP with a very good response. I feel fortunate that it is almost 4 years from one treatment to the next.
CLL is really the “Good Cancer” to have as related to patient advocacy. Chaya, thanks for all you do for us.
Tom
Many thanks again Chaya – as usual an eye opener, particularly with regard to the carcinogenic effects of Cyclophosphamide.
At present, I am sitting here, aged 63, having happily heard today that I’ve got yet another 3 months remission after treatment with FCR 18 months ago. Fingers crossed for a long continuance, and thanks again – forewarned is forearmed.
Lawrence
Cornwall, UK
Another hidden ‘cost’ of chemo drugs is from damage to short term memory, or ‘chemo brain’ as I heard it called today. This seems to be the somewhat permanent damage to the short term memory post chemo.
It is a fairly essential ability to have in most jobs and in attending a post treatment cancer stress clinic, everyone there seemed to be suffering from memory loss, sometimes years later. It was so bad in some people, they’d had to give up their jobs. I’m finding it really difficult to operate as before, and yet this was never even discussed as a possible result of the drugs.
Being able to earn a living especially in us younger patients, surely has an impact on the post chemo ‘costs’.
Chaya,
I meant precisely that the healthcare costs for the SAME cohort of patients after therapy would be expected to increase by virtue OF their therapy. Many of these patients were accumulating tumor burden prior to therapy, but not necessarily being treated for things such as neutropenia or anemia. They certainly weren’t receiving chemotherapy drugs or supportive care during this time frame (at least not each and every one of them). Comparing costs before/after therapy is disingenuous
In the months prior to my first and second treatments I felt well and my only costs were those of periodic visits and laboratory studies. During and after treatment there were many more lab tests done, many more routine visits initially and also the cost of prophylactic drugs as well as the cost of a single dose of erythropoietin. Had I required more care for anemia, infection, etc it is axiomatic that these costs would have been even greater.
That was my point…the only reasonable comparison would have been of 2 similar cohorts who received DIFFERENT types of therapy and were then followed as to outcomes and costs AFTER their different therapies. To my mind, therefore, my other arguments are not moot.
Once again, the issue of cardiac toxicity was not properly addressed in this paper. Older people with underlying heart disease are more likely to manifest problems when stressed by any therapy. The only meaningful comparison would be between two reasonably similar groups who were followed after they completed DIFFERENT therapies.
I do agree that the recognized benefits of appropriate prophylaxis are gratifying, but we all know that too many people do not receive appropriate prophylactic therapy in the real world.
Be Well,
Rick
Good article. It would be nice if people could take a chemotherapy like Campath, beat back the cancer for a time, and go on their merry way and live normally until the next time. That does happen and helps alot of people, but clearly side effects can lead to multiple health effects and/or hospitalizations, especially after the body is worn down from years of cancer and chemo. I have seen it happen, however with Fludarabine and especially Cyclophosphamide. What if people can’t afford the side effects? There is the cost of chemo, and then what follows. There is also the exhaustion of dealing with one thing after another. All one can do is hope everything will work right, as well as not wipe people out financially. I hope for a future with prevention or a cure, thus avoiding the healthcare boondoggle of today.
Ojibwak
Re: Chemobrain
At the 2008 Annual Meeting of the American Academy of Neurology two small studies were presented which offer another perspective on this issue. (Find links at http://www.s4om.org/div1/chemobrain.htm)
The studies suggests that “chemobrain” is not caused by chemo (or radiation) but by the patient’s response to the stresses of diagnosis and treatment, worries about the future, changes in interpersonal relationships, alterations in daily routine, etc. The researchers found comparable cognitive impairments in breast cancer patients receiving chemo or radiation and in patients who received neither chemo nor radiation.
There is no question that the cancer experience often results in cognitive impairment. Yet another factor not analyzed is response to surgical anesthesia. Many surgical patients, not just those with cancer, experience significant short and/or long term cognitive impairment.
What we do not know can hurt us.
The study that got Campath FDA approval for frontline status in CLL compared toxicity profile of Campath versus chlorambucil. The cardiac toxicity of Campath was 10 to 1 compared to chlorambucil (147 patients in each arm).
This is a quote from the company website
“Cardiac dysrhythmias occurred in approximately 14% of previously untreated patients. The majority were tachycardias and were temporally associated with infusion. Dysrhythmias were Grade 3 or 4 (ouch!!) in 1% of patients.”
My point is this: since potential for cardiac toxicity in the context Campath therapy is not widely known, are patients being screened for it ahead of time, monitored for it after the fact or the data reported to FDA in post market surveillance? Would older patients with existing cardiac issues be better off with good old chlorambucil and take their lumps with palliative care?
http://www.campath.com/pdfs/2009-08-Campath%20US%20PI.pdf
Chaya,
Thanks for an interesting article.
Thanks again for a well analyzed discussion.
Thank you, Chaya, for analyzing the study and getting the comments going. I really like your writing style.
Thanks to all of the commenters for your knowledge and experience and your willingness to give us the benefit of that.
Chaya,
Thank you for a very important article.
Monique
As always, thank you.
Beverley
Chaya,
Have been following your useful CLL Topics. Not only
do you enlighten us all ( I am CLL remission
individual who has been Cytopenic then & now with counts
still low but as good as will probably get), had the
fungal pneumonia- now on prophylactics-, fibrllation episodes, etc., etc. Still in remission & a survivor- so no major complaints. Ironically, I have been working on art work with abacuses as an uderlying theme & there you have one at the end of this topic re money.
How ironic! I started the abucus series a while ago. Will have to send some images sometime. Again many
thanks – Sonia
It is good to look at the financial costs of healthcare. However, I wish the study had also looked at the human costs of treatment. For example, how many of the 81 patients had cardiac costs before and after treatment? Seems like it would be rather easy for the authors to do.
This abstract provides an interesting topic of discussion related to the cost of treatment (human and monetary). However, due to the nature of its design, it is very difficult to draw any conclusions from the data presented.
My own experience with campath vs other chemo-therapies has been just the opposite. My first chemo experience (CFAR) had no additional costs. My second chemo experience (OFAR) included additional medical costs (platelet transfusions and related lab work) and loss of income (unable to work while waiting for the return of an adequate platelet count). My third chemo experience (bendamustine) also required additional medical costs (neupogen injections and additional lab work).
Perhaps the costs would have been different if the order of my treatments were reversed.
I had no cardiac symptoms with any of the treatments but I also had no history of cardiac disease.
I am now post-transplant but have another interesting cost antidote related to prophylactic medications. New post-transplant neutrophils can be sensitive to commonly used prophylactic antibiotics. Mine have been sensitive to bactrium and penicillin. Both of these very inexpensive medications have resulted in profound neutropenia requiring very expensive neupogen injections and extra lab work. It also increased my risk of developing an infection during the periods of neutropenia. Fortunately I remained healthy during these periods and my neutrophil count has stabilized on dapsone. I just offer this as an example of how a very inexpensive and seemingly positive action can have a profound effect on medical and potential human costs.
Steven
Hi Chaya,I personally feel the group was too small to generalize the results to the general population of CLL patients. I also feel it was rather poorly designed. I could not determine if Campath was the only drug they recieved, whether they had had treatments before the Campath. There was also no mention of their status regarding gene mutations and other factors.
In my husband’s case. He had had no treatment for 3 months of anykind and only had prednisone for 8 months before that. He had had 2 short rounds of chlorambucil and prednisone beofre that. The first Dr. had never done a bone marrow. He had no explanation as to why he was having such low hgb and platelets. I’m sure he knew but never explained. After I started reading your CLL Topics, We sought out MD Anderson.
In Nov. 2004 he started CFAR. He took 4 rounds. He had many complications during and after the completion of the treatments. No heart problems.It has not been a picnic for sure. After almost 5 years, he still has a tendency for infections with harsher courses. We praise and curse CFAR in the same breath. He is still in complete remission, It will be 5 years in March 2010. He had to be treated with a count of 48,000 because his bone marrow was packed with lymphs. His hgb was 9 and platelets about 50,000. He chose the treatment and the risks were explained. I wish they had known at that time to give prophylaxis for fungal infections. Thanks for all you do. Disy Yarbrough
I had 2 rounds of maintenance treatment with Campath w/o any ill affect 6 months later. I have been in remission for over 8 months. Now, Jan. 1010, I am no longer in renmission. My lymph nodes are enlarged and I will need treatment. I am waiting for the bone marrow results and tomorow, I will be consulting with a surgeon to remove or take biopsy from one of my nymph nodes!
Ronald I.
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