Take Away Points:
- Treatment with immunotherapies, particularly monoclonal antibodies (mAbs) have improved treatment outcomes in CLL.
- mAbs are more focused than chemotherapy, but still may have non-cancer targets.
- Immunomodulatory drugs (IMIDs) have many activities and how and why they benefit CLL is still not defined.
- Immunotherapies are now and will continue to be a part of therapeutic cocktails aimed at disease control, and eventually a cure for CLL.
Monoclonal antibodies (mAbs) have revolutionized the treatment of most lymphomas, including CLL (chronic lymphocytic leukemia). It was the addition of rituximab to the fludarabine and cyclophosphamide chemotherapy combination that first showed a survival advantage for any CLL therapy. Since then, that happy story has been repeated many times, almost always with one of the mAbs as one of the co-stars.
Infusion reactions are a very common and unpleasant adverse event with most mAbs, but can usually be anticipated, and proactively managed. They pose much less a risk after the first infusion. Even though mAbs are not damaging to the marrow and the cell growth in general, they can lead to low blood counts, especially neutrophils, and to infections, including reactivation of dormant infections, such as hepatitis B.
Still today, it would be the extraordinarily rare patient who would not benefit from adding an antibody to our chemotherapy protocol. Their role in combination with the novel signal blockers is still being defined. New antibodies such as those directed again ROR1 promise to be even more focused.
Immunomodulatory agents or IMIDs such as lenalidomide are not yet approved in CLL, but offer the prospect of disease control on their own or in combination with other targeted agents, often in the absence of any cytotoxic chemotherapy. Why and how they work is not fully understood, but they clearly benefit several other blood malignancies (i.e., multiple myeloma and myelodysplastic syndromes) and offer promise in clinical trials in CLL.
They are not trouble free either and are associated with some potential problems including but not limited to infections, secondary cancers, tumor lysis syndrome (TLS), tumor flare, low blood counts, fatigue, blood clots, and of course must NEVER EVER be taken if there is any chance of pregnancy. Please be sure to read the label carefully, but take the information in context. These drugs have been very helpful to many with CLL in clinical trials. Here is a link to the Package Insert for lenalidomide.
Immunotherapies are a growing part of the CLL armamentarium and often offer a gentler approach on their own and may add significant punch to other therapies while adding little toxicity.
Take a look at the video of my monologue on immunotherapies is different from others in the therapy section as it is completely unscripted and as result I believe is very focused and directed, much like the drugs it reviews. It also covers significant material not covered in this introduction text.
Brian Koffman 6/14/15