Treatments for elderly CLL patients

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Published: 24 Mar 2011
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Professor Clemens-Martin Wendtner – University of Cologne, Germany
All chronic lymphocytic leukaemia (CLL) patients used to be treated with standard chemotherapy – chlorambucil. Professor Wendtner, speaking at the Blood Cancer in the Elderly European Expert Forum, says this has now changed and it is important to first assess comorbidity and then define the appropriate treatment for the patient. If the elderly patient is fit and could stand more treatment then chlorambucil, he could be offered a chemoimmuno therapy, which would be a combination of chemotherapy and an antibody. The combination regimen of FRC (rituximab + fludarabine + cyclophosphamide) is becoming increasingly popular as a frontline treatment for CLL for fit elderly patients.

Blood Cancer in the Elderly: European Expert Forum, Rome, 19—20 March 2011
Professor Clemens-Martin Wendtner (University of Cologne, Germany)

Treatments for elderly CLL patients

More now from here from Rome and the conference on Blood Cancers in the Elderly. Now we are going to be talking about the most common cancer in the west, and the most common cancer in the elderly, with Professor Clemens-Martin Wendtner. Professor Wendtner, what is the issue with elderly patients with this particular cancer, chronic lymphocytic leukaemia?

In former times we used to treat all patients with a standard chemotherapy called chlorambucil; nowadays we are aware that it is very important to assess comorbidity first, and then to define the appropriate treatment, so if an elderly patient is fit he could stand more than just chlorambucil so this patient we would offer, for example, also a chemo-immunotherapy, so a combination of the chemotherapy and an antibody. Otherwise if the elderly patient is unfit chlorambucil would be the standard.

Chlorambucil is still being used in older patients quite commonly but the FCR regimen of fludarabine, cyclophosphamide and rituximab is now increasingly popular. Can you tell me why there are changes and what your accounts and what your advice would be about looking at older patients?

FCR, as you mentioned; the triple combination based on fludarabine, cyclophosphamide and rituximab, has been approved by the FDA and also by the European authorities for front line treatment in CLL, and this includes also elderly patients if they are fit. Using FCR we can show not only an improvement in progression free survival, so disease free survival, but also in overall survival so this would be the option for an elderly patient being very fit.

You have been working with the German CLL Study Group and I know you have had a big new study coming along, but this is a disease with great variability. The outlook can be quite different from patient to patient. What would you advise doctors to do when they meet the average patient?

Before the initiation of treatment we propose to assess a cytogenetic marker profile, so based on cytogenetic aberration we know that there are patients, roughly 8-10%, that have a very high risk or quite a high risk of disease. These patients, if they are fit, would be moved to transplant very quickly, otherwise the majority of patients, 90% roughly, they will most likely benefit from standard treatment.

There are markers of very poor prognosis, the 17p deletion I believe is one of them, but is it clear from other genetic markers who your patients are, which are the ones that you should treat more intensively?

As you mentioned, the deletion of chromosome 17p is the most accepted cytogenetic aberration.        We also know mutation of the p53 gene located on chromosome 17 is, in the same sense, an ultra-high risk aberration, otherwise we would not adapt treatment based on less important cytogenetic risk parameters.

But you said you would adapt a treatment depending on comorbidities.

That’s right.

Could you expand on this and the main issue of course that you are talking about here in Rome, comorbidities that affect older patients?

Right, we introduced a semi-objective quantitative assessment scoring system called the Cumulative Illness Rating; a scale system, scale score. This has been introduced as a fourteen point bullet         questionnaire assessing comorbidity and cancer patients or leukaemia patients with a CIR score above 6 would be assessed to be not so fit and these kinds of patients would get a less aggressive chemotherapy. On the other hand, patients with a low CIR score would be offered an aggressive chemo-immunotherapy.

To what extent is age the issue, as compared with comorbidities for instance?

Age is no more the discriminator in this case, it is comorbidity. So in our trial we had an 81 year old gentleman that had been offered also the FCR, the triple combination. This gentleman was jogging, was a very fit elderly CLL patient but we can prove that, based on this scoring, if you select your patients they will stand the treatment quite well. The side effects are not different to younger patients that are fit, and also the outcome is very similar.

And could you very briefly tell me about the new randomised study, CLL 11, that you are embarking upon right now? What is that going to tell you; it does include immunotherapy doesn’t it?

The CLL 11 trial you mentioned is the trial for the elderly but unfit patients, the so-called Slow Go patients we call them.  The basic treatment is chlorambucil but in the experimental treatment arms we add an anti-CD20 antibody, on the one hand it is rituximab, on the other hand it is GO101; this is a new type 2 CD20 antibody. So we try to also introduce minor chemo-immunotherapy to the elderly ones that are not as fit, but we have to await the results.

Clearly that will be very interesting when it comes out. Right now today though, to sum up, what would you advise busy cancer doctors to be doing about their patients diagnosed with CLL?

First they should assess whether they see a fit or less fit patient. Based on this they should offer chlorambucil as a standard for the less fit ones, also clinical trials. If they define that the patient has no severe comorbidities they should even dare to offer more aggressive treatments including also antibodies plus chemotherapy.

So how much benefit in terms of outcomes then, finally, do you think we could see with better selection in CLL?

I think we could spare side effects from unfit patients if they only get treatment that is adapted to their fitness. On the other hand we could also offer effective treatments in the elderly ones. Nowadays we tend to under-treat elderly patients and this is just an approach to get the best, most efficient but also tolerable treatment to the elderly cancer patient.

Thank you very much for being on

Thank you.