I just had my three month check up. My doctor informed me of some new and upcoming treatments. I thought I would share:
There are several new treatments that are available for the treatment of CLL. In addition to the standard chemo-immunotherapy combinations of the past (These are regimens like Fludarabine-Cytoxan-Rituxan and Bendamustine-Rituxan) there are also newer anti-CD20 monoclonal antibodies with a drug called Gazyva (obinutuzumab). There are three “newer” oral targeted drugs for CLL therapy. Ibrutinib and Idelalisib have been out for a few years and help to block different areas of the b-cell receptor. The newest FDA approved medication (approved in April) is venetoclax which targets a protein called BCL-2 (This drug is not used up-front at this time as it is only FDA approved for people with a 17 p deletion). So there remains several newer options for the treatment of CLL.
These medications are typically used as single agent by themselves. (Idelalisib (Zydelig )is actually FDA approved in conjunction with 8 doses of Rituxan). Obinutuzumab is an injection which runs over about 4-6 hours.
Have any of you tried these treatments?
I hope everyone is taking care of themselves!
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Jemisavs5
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Thanks so much for sharing. As Cammie says, you're in America so may differ with availability but isn't it great to hear that there are new options becoming available all the time. It bring us so much hope for our futures. Thank you.
Venetoclax and other approved novel agents can be used front line in non-17 deleted patients although I would consider this only if you are under the care of a CLL specialist. Not all insurances cover these agents for such patients , but some do, so worth asking your CLL specialist about. Idelalisib however should never be used front line.
I am blessed to be on Ibrutinib as my first line treatment. Now I just keep my fingers crossed that it will be effective for a long time. Have to give those wonderful researchers time for the next breakthrough!
For the first treatment, especially for younger and more fit folks, there's a very convincing argument that chemoimmunotherapy is still the best choice over some of the newer agents, sexy as they may seem.
The argument is that with BR or FCR for first line treatment, it's six rounds and then you're done. You'll get a remission of several years at least and perhaps longer, especially for younger mutated patients that do FCR. On the other hand, once you start one of the new targeted agents you can't really stop for the rest of your life unless you're having severe side effects and need to switch to a different one. The very long term effects of the new targeted drugs are not yet known.
For first line treatment, and as a 65 year old fit guy, I buy the argument that six and out is the way to go. I chose BR as my first treatment, tolerated it easily, and got a remission that's holding steady. I don't have to put any drugs in my body right now. The longer my remission lasts the better -- I'm back in watch and wait until relapse occurs. When I need treatment again, there will be even better and more easily tolerated drugs than the pills now on the market.
Other views exist, of course, but thought I'd throw mine out there.
(To make it more complicated, it was part of a Phase III clinical trial that included Idelalisib for previously untreated patients. I could not tolerate the Idelalisib and failed out of it early. The treatment included six full courses of BR, which I tolerated with minimal side effects. I give BR full credit for my solid partial remission.)
Eighteen months after I finished treatment, I'm still in remission. Blood numbers are starting to rise very slowly but they're still all within normal ranges. I feel perfectly fine, I'm fit, and very active. Happy, too!
I don't regret my choice at all. The time will certainly come when I need treatment again but the longer I wait, the better. The science is moving very fast -- acalabrutinib could easily be approved by the time I need treatment again or even third-generation targeted agents I don't even know about. And in the meantime, I don't have to subject my body to any drugs at all.
I know from my extremely adverse experience with Idelalisb in my trial that these new targeted agents are not necessarily a walk in the park. Idela attacked my liver as well as my small intestine and I still have some lingering negative effects from it. My opinion is that everything is not yet known about these new agents, including possible linkages to secondary cancers, because they haven't been around long enough for long-term effects to show up. I think they're wonderful but aren't magical. The lifetime commitment to them also gives me pause.
When the time comes, I'll definitely do another clinical trial just so I can help contribute data to the emerging science. Presumably I'll end up with a brand new targeted agent with a lower toxicity profile and fewer side effects than those available now. But hopefully it'll be another few years before I need it.
Best of good luck to you with the FCR! I hope you're one of the ones who finds it pretty easy to tolerate. Most of all, I wish you a very long and stable remission when you're done. If and when you ever need treatment again, it'll be a completely different -- and better -- landscape than we have now, with even better drugs than anyone currently imagines.
Take care and keep us posted. Also, please feel free to contact me via a private message if you would like. Best regards --
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Sending you best wishes during treatment. Most especially, I hope you get nice long remission and that exciting new advances in the science happen in the meantime!
The problem with chemo is the increased risk of another cancer down the road. Combinations of newer therapies are in some cases getting deep responses with MRD negativity (>50% with some therapies) and some people are then stopping therapy. A recent video by Dr Furman was posted on this site in which he said if someone wanted chemo they could "find another doctor". Everyone is different in regard to what risk they are willing to assume for potential benifit. Nothing is lost by trying the non-chemo therapies if they are available and potentially have great advantages without increasing risk of more agressive leukemias and MPN.
I'm confused about the risks of secondary cancers. I used to think there was less risk with non-chemo treatments, but just recently I saw "second primary cancers" listed as a side effect of Ibrutinib. (On a site from Pharmacyclics LLC and Janssen Biotech, Inc. imbruvica.com/cll/side-effects )
Has any research been done to compare the risks of second cancers when on Ibrutinib longterm as compared with the risks after standard chemo-immunotherapy?
I realise that merely the fact we've got CLL means we're more likely to get other cancers, even before we've had any treatment. Just the passing of time (ie the aging process) increases our risk of course... as it does for everyone, whether they have CLL or not. But it would be interesting to see some statistics comparing new cancer cases in CLL people who are non-treated, with those who are treated with the various different chemos and non-chemo regimes.
I'm not convinced that nothing is lost by trying non-chemo therapies. I took Idelalisib in 2015, which worked brilliantly at first but when I stopped it (for a short time because of a rash), my spleen ballooned back up and ruptured. My family were called from far and wide because hubby was told I might not survive. With a mutated IGVH and a 13q deletion, I would probably have done better with FCR.
Idelalisib is better understood now and would not be given as a first treatment. However, it made me realise that there is still a lot to learn about these new drugs. They don't have the track record of the older treatments and as time passes, more of their limitations are becoming known.
This dilemma is close to me at the moment, because I'm needing further treatment and am not sure whether to try and find a non-chemo option again, (not sure that will be easy in the UK), or whether to go back to some well-tried and tested chemo-immuno therapy.
Wishing you all the best as you continue with your Venetoclax treatment,
I haven't looked at the data regarding risk of second cancers and Ibrutinib use. The question is whether or not there is cause and effect, or whether there is just a statistical correlation. The issue is fraught with difficulty due to many confounding variables. As you mentioned, age is one. Also was there prior treatment with chemotherapy? Is there a genetic familial predisposition in a patient to multiple cancers? Has there been an exposure, such as we see with Agent Orange, that predisposes to multiple cancers? Has the patient achieved MRD negativity with Ibrutinib, which is not likely and so the patient still has an impaired immune system?
The question I put to my CLL specialist, who is also an immunologist, is "if I achieve MRD negativity with a non-chemo treatment, will my immune system recover and normalize?" He said yes, it would be like taking a tarp off the lawn. That does not mean I could not get a second cancer for any of the reasons listed above after taking Venetoclax. And since I have a very strong family history of cancer and have already had a second cancer (breast), I could very well get another cancer. I wanted to minimize any risk for another cancer from my CLL treatment. We know the potential collateral damage from chemotherapy because it affects bone marrow and DNA. Will we see other problems down the road with the newer target therapy? Only time will tell but due to mechanism of action, it seems much less likely.
As far as the "nothing is lost by trying the non-chemo therapies" statement, I did not mean to imply there was no risk with non-chemo therapies. Every therapy has risk of potentially great harm. I was referring to the fact that once the decision has been made to treat, you haven't burned any bridges in terms of other therapies that can be used down the road for recurrence, including chemotherapy if desired, and have avoided the potential impact on bone marrow and DNA. It all comes down to what risk you are willing to assume for the potential benefit, and what treatment is available to you. Everyone is different in what that is. In many part of the world only FCR is available outside of a clinical trial.
Thank you for the well wishes and wishing you well also as you plan your treatment strategies.
I realise that the issue is very complex – much more than I first thought. As you say, even if we did have statistics on the frequency of second cancers, they might not be very significant as there are so many variables.
Thanks for bringing up the question of damage to the immune system – which is so important. Very encouraging that your doctor said if you achieved MRD negativity with a non-chemo treatment your immune system should recover and normalise. I realise this is much less likely to happen after chemo treatments, due to potential damage to bone marrow and DNA etc.
I presume you could safely stop the treatment (Venetoclax in your case), once you’d got MRD negativity? Would stopping the drug be necessary to enable the immune system to recover?
My understanding of these things is very limited, but I’m trying to learn more, so I can make the most informed decision on my own treatment. I’m at a UK centre where they do a lot of clinical trials but I don’t think Venetoclax will be an option for me. Ibrutinib may be, but I’m being rather put off by hearing of people’s problems with it.
Thanks again for taking the time to give me such an in-depth reply.
The plan is to eventually stop Venetoclax if and when I become MRD negative with a complete response. If I don't get to MRD negativity we will add another non-chemo therapy, probably a monoclonal antibody and then stop therapy if MRD negativity is achieved. I didn't ask specifically about whether it is necessary to stop Venetoclax in order for the immune system to recover. I think it would depend on whether or not there was any neutropenia during the treatment. This doesn't usually happen with treatment naive patients and so far my ANC has been excellent. All my immunoglobulins have always been normal and continue to be normal on treatment.
Best wishes on your CLL journey. Hopefully just the right clinical trial will be available to you.
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Promising clinical results for new drug combination for CLL (GA101 plus Chlorambucil)
Survey for CLL patients having taken Venetoclax or Acalabrutinib
Clinical trial results & reviews of new treatments for CLL written in easy to understand terms 
Ibrutinib +venetoclax
