Advances in the treatment of CLL

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Published: 18 Feb 2011
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Prof Kanti Rai - Long Island Jewish Medical Center, New York, USA
Prof Kanti Rai discusses advances that have been made in the treatment of chronic lymphocytic leukaemia (CLL). Key research presented at this years ASH congress has demonstrated that previously untreated patients who do not want or are unsuitable for chemotherapy can be successfully treated with a combination of rituximab and lenalidomide. In addition to this a number of studies have been presented which have confirmed FCR (fludarabine, cyclophosphamide and rituximab) as the most effective frontline treatment for CLL and there have also been positive results for new tyrosine kinase inhibitors used to treat patients who do not respond to FCR. Prof Rai also explains how the low toxicity levels of bendamustine makes it particularly suitable to treat elderly CLL patients, discusses the use of lenalidomide, elotuzumab or rituximab as maintenance treatment to help patients avoid further chemotherapy, speaks about the movement towards personalised medicines for CLL and looks ahead to the IWCLL (International Workshop on CLL) congress to be held in Texas on 28-30 October 2011.

2010 American Society of Hematology Annual Meeting 3rd - 7th December


Interview with Prof Kanti Rai - Long Island Jewish Medical Center, New York, USA


Advances in the treatment of CLL


IV         Interviewer

KR        Kanti Rai



KR        This year’s CLL meeting… CLL sessions, at American Society of Hematology, is particularly a very exciting, very important, and to my mind, is some kind of a landmark in that we have embarked upon a completely new era, as it were. Because everything seems to be coming together. In the preceding decades there was a huge amount of activity… investigations, clinical and bench based, of developing good indicators, or markers, of prognosis, adding to clinical stage. But this meeting, starting early in December 2010, everybody is noticing that now things are clearer. The prognostic markers on molecular basis, as well as cytogenetic basis, are integrated and reliably integrated with the clinical factors. And the treatment approach to the patients is now a realistic risk adapted manner.


So, at this meeting, there are a number of things that are emerging, that in the previously untreated patients, which we called frontline treatment. For those patients who do not want to have any stigma of chemotherapy, there is a combination of the monoclonal antibody rituximab plus an immune modulating agent, lenalidomide, in frontline. Which is very exciting. The earlier data, which is still… the studies are still in progress, reveal that this will be an important contribution in frontline treatment for those people who either do not want the traditional chemotherapy or are not eligible for various reasons such as, age and comorbidities. So, that is exciting. There are a number of studies confirming frontline FCR, fludarabine, cyclophosphamide, plus rituximab, and similar to FCR, which confirm that… what Michael Keating in Euston and Michael Hollick, on behalf of the German CLL study group have demonstrated quite convincingly. That that combination has become the… practically the standard frontline, most effective treatment.

At the level of previously treated patients, we now can go by some of the molecular criteria. That those patients who do not have, by fluorescence in situ hybridisation or FISH technology, 17P deletion or P53 mutation, or 11Q deletion, these patients can be approached. And those who have already received FCR type of treatment, with newer agents which are some of the tyrosine kinase inhibitors, CAL101 and another drug, which is a Bruton tyrosine kinase inhibitor, BTK inhibitor. They are showing exciting and practically extraordinary level of activity, in that bulky tumours are melting away, the cells from those big lymphoid masses, perhaps, are going into the peripheral circulating blood. So, initially, there is a further increase in the blood lymphocyte numbers. But that you can handle, because now they’re… those cells… leukaemic cells, are becoming more accessible.


Therefore, for those people who did not have, until yesterday, much to be treated with, there was not much available. Now we are doing something very important. And the emergence of Bendamustine in the treatment area, particularly in combination with any of the anti-CD20 monoclonal antibody, either Rituximab or Ofatumumab, are demonstrating to have great degree of activity with very tolerable toxicity profile.


IV         And that’s particularly relevant, I guess, in a disease of the elderly.


KR        That’s right.


IV         Trying to reduce toxicity.


KR        And, disease… as you well know CLL is essentially a disease of the elderly; 80% of the patients with diagnosis of CLL happen to be in the elderly category. And, therefore, it is very important to have a relatively low myelotoxicity-containing drugs, combined with monoclonal antibody. There have been a couple of interesting reports of maintenance treatment, either with Lenalidomide or with the Alemtuzumab or Rituximab, which have demonstrated enormous level of activity in keeping the patients away from the need for more chemotherapy. So, it’s an exciting time.


IV         It’s an exciting time, yes. And very different to 20 or 30 years ago.


KR        Or as recently as 10 years ago.


IV         Interesting if you look at the multiple myeloma arena, there’s a great deal of interest in pharmacogenomics and targeted treatment. Do you think we’re now at the stage where we have enough armourmentarium of new drugs in CLL, where we can start looking at more personalised medicine in CLL?


KR        Absolutely. I will say absolutely, but, to give it qualifying, add on to my statement. And that is, that direction is now starting. Whereas, in multiple myeloma, they have the advantage that they’ve already gone after this after the proteasome inhibitor drugs discovery. But, now we are discovering targets of CLL leukaemic cell. And, therefore, it’s only a matter of time. I would say within the next three to five years. That anti-BCR, B-cell receptors, which are the driving forces of leukaemic proliferation, that going after the BCR will become the challenge next year.


IV         And looking ahead to next year, of course, is the next IWCLL Congress workshop, scheduled for September in Houston. I wonder if you’d like to just mention a few words about that?


KR        International workshop on chronic lymphocytic leukaemia, or, as you said, IWCLL, has become the go-to point for all colleagues who are investigating CLL today. As you probably know, we meet every two years in a different country, by rotation. And in 2009 we met in Barcelona. And practically 2000 people showed up because, just when we started with IWCLL, with Doctor Jacque-Louis Bernait as the leader in Pitié-Salpêtrière Hospital in Paris, we were 20 people.


IV         It’s come a long way.


KR        And now, to see 2000 persons, and in different specialties in medicine: immunology, genetics, clinical epidemiology, family medicine. It is very exciting. And this 2011 meeting, as you just said, will be in Houston, Texas, in the US, and will be in September. And we are very, very excited because this will reach out to all… not only the investigators in this field, but all the patients. And patients see no barrier between political or geographical borders in countries or continents. People from all over watch for IWCLL.


IV         Kanti, Thank you very much for your time. Very interesting.


KR        It’s a pleasure. Thank you.