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Blood Cancers Video Library: CLL – Is there still a role for chemo and who should get chemo?

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GRACE joined a number of top faculty in the area of hematology in Whistler BC, for the 3rd Annual Summit on Hematologic Malignancies.  Jennifer Brown, MD, PhD, Director of the CLL Center at the Dana-Farber Cancer Institute spoke with GRACE and provided a provoking and educational discussion on whether or not there is still a role for chemo, and who should get it.  Dr. Jennifer Brown

We invite you to watch this first video from our Blood Cancers Library Video collection

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Chronic Lymphocytic Leukemia

Is there still a role for chemo and who should get chemo?

Jennifer Brown, MD, PhD, Director of the CLL Center at the Dana-Farber Cancer Institute

 

For this potential FCR [fludarabine, cyclophosphamide and rituximab] group with mutated IGHV, it’s really very important to consider getting FCR as upfront therapy because this may be a chance at cure, and in any case it’s a better than 50-50 percent chance at being in remission for ten years on no further therapy, which is really very appealing compared to being on chronic therapy for all that time. And with the kinase inhibitors we don’t know actually the durability, we don’t know what will happen when one’s been on them for 5 or 8 or 10 years, because we don’t have that length of follow-up.

So it’s very important to find out your mutated or unmutated IGHV status as you consider first-line therapy, especially if you’re younger and don’t have many medical problems. For the older patient subgroup, or those who have multiple medical problems, it’s a little bit more complicated, because it was never found that fludarabine-based therapies were any better than the older drug, chlorambucil. Most of our studies of chemotherapy for patients in this group have used chlorambucil as a basis. Now, the most recent studies showed that adding a new antibody called obinutuzumab, which is also targeted against CD20 like rituximab but is a newer drug which is more potent in CLL. Obinutuzumab with chlorambucil actually results in a median what we call progression-free survival, namely alive and still in remission, of 31 months, and people don’t need treatment again for over four years. This is really for what is a very benign, six-month therapy.

Who should consider that? For patients who have low-risk disease, like mutated IGH, who don’t have any high-risk chromosome abnormalities, like 17p or 11q, and who would like a time-limited therapy rather than potentially indefinite therapy, it could be quite reasonable to consider a short course of this chemotherapy and then hopefully get four years or so without needing more treatment, rather than committing to ongoing indefinite kinase inhibitor therapy.

For people with higher-risk CLL, the 17p or 11q deletions or the higher-risk unmutated IGH, it’s a little bit less clear that going with the chemo-immunotherapy would buy as much time before having to start on a drug like ibrutinib. For those people it would be potentially more relevant to start on ibrutinib sooner. If one does start on ibrutinib one needs to be aware of some of the chronic side effects that develop over time. These can include swelling, aches and pains in the joints and legs which can be quite irritating, some diarrhea and muscle spasms. There are some medical problems associated with it as well – about a five to ten percent chance of a heart rhythm abnormality called atrial fibrillation, and some incidents of bleeding, most of which is just easy bruising but which can occasionally associate with more significant bleeding.

In summary of who should get chemotherapy in CLL, fit, young patients who have favorable mutated IGH and low-risk chromosomes clearly should get FCR in an effort for what appears to be even potential cure, with a 60 percent chance of long-term remission. Beyond that group, a value judgment is really required as to whether one wants to do a fixed-duration of therapy for some years off therapy or to commit to ongoing chronic therapy which may have some ongoing chronic side effects but will likely control the disease for an extended period.

 


 

 

 


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