"George Follows, a UK CLL expert, provides his thoughts on updated data from key studies in chronic lymphocytic leukemia (CLL) that were presented at the 2021 meetings of the American Society of Clinical Oncology (ASCO), European Hematology Association (EHA), and International Conference on Malignant Lymphoma (ICML).
These conferences have provided reassuring updates and new data for hematologists who treat patients with CLL and certainly for the patients themselves. For the first time in CLL, there are comparative data showing how one BTK inhibitor may differ from another, and there has been extended follow-up of some of the landmark trials of BTK inhibitors. In addition, there are new data on BTK inhibitors combined with venetoclax, a new way of taking doublet therapy forward into the future."
Lots of information here and too much to summarise in a few paragraphs but well worth looking at. There will be something for everyone here.
Jackie, this post does not directly relate to your post, but there are overlaps, and in any case I would appreciate your thoughts.
The ASCO, EHA,ICML, summary seems to cover all combinations except Venetoclax alone.
I am in the early stages of a V+R treatment, post Ibrutinib relapse. I am not tolerating the V ramp -up (low Hgb, platelets and neutrophils) and am holding at 50mg a day, which seems to be working at least in terms of diminishing lymph-node bulk and good WBC and Lymphocytes in my blood.
My Ig levels are almost non existent (though I'm not prone to infections), and my Covid jabs were negative for antibodies.
I am wondering, following Eugene's post the other day attaching an article printed in the peer-reviewed American journal ‘Clinical Advances in Hematology & Oncology’, April 2021, written by Richard Furman, whether the Rituximab is likely to do me more harm than good, and I'm having a chat with my consultant tomorrow about just this.
You've always given such good advice on this site before, so I wonder if you have any thoughts on my predicament.
Roger, you’re right the monoclonal antibody can cause additional problems. It quickly removes all the circulating B lymphs plus those in the bone marrow and it can take many months to recover any immune functionality. It does not do a good job of removing B lymphs in the LNs. Clearing the bone marrow can support it to make blood cells providing you have enough reserves and you don’t have too much suppression from the V.
The difficulty for doctors is thatV+R is approved by NICE for R/R CLL and that’s what they have to use …,,. at least to start with.
I would have thought that it’s at least worth having the discussion with your Dr about the R but I think he’ll say you are sensitive to the V and that is causing your low counts. Stopping the R would however, looking further ahead, help with your immune response inc immunoglobulins.
Very helpful, thank you Jackie. I will let you know how my chat goes tomorrow and what happens thereafter.Fortunately I have a good relationship with my consultant....until now at least!!
Jackie, I'm sorry to hear that the 3rd jab left you feeling unwell. Hope you're feeling OK now, None of my 3 jabs, nor last week's flu jab, had any effect on me. Who knows if that means anything?
I said I would let you know how my consultant reacted to my suggestion that I should discontinue the Rituximab infusions at least for the time being. I'm so lucky to have a consultant who is open and happy to discuss things.
He recognised that my immune system was very weak, and that Rituximab would worsen it, all at a time of Covid and going into winter. Conversely of course he reminded me that the only evidence of long PFS was after V+R treatment. Anyhow we agreed to delay the Rituximab infusions for the time being, to regularly monitor my condition and review the decision whenever appropriate. He said he would clarify whether the use of Venetoclax as a long term mono treatment, if necessary, would be possible, (V+R is usually time limited), but all that's for the future.
Quite separately, I had MRI and CT scan results from the Marsden this week (they are monitoring me post melanoma therapy), and my consultant there commented (in addition to giving me an all clear re the melanoma), that my lymph-nodes had significantly reduced in size since the last scan (3months), and that is on only 50mg venetoclax daily. I do wonder whether the effectiveness of lower than recommended doses of the BCL2 and BTK inhibitors are ever properly trialled. Just a thought.
That’s such good news Roger, both re the Rituximab and the reduction in the size of your lymph nodes. I’m not sure if long term mono therapy with Venetoclax is still available but that sounds good if it is. One of the reasons that fixed term VR was approved was that it was argued that it would be cost saving to the NHS because previously people were on Venetoclax indefinitely.
Regarding the dose being trialled, those things are decided at the Phase I study stage where they look at how different doses are tolerated, their effectiveness and the side effects. I’m pretty sure there will be some snazzy science behind it.
Lots of people report excellent responses at lower doses than the 400mg that is recommended. Whether you can become negative for MRD at that dose is another matter and that negativity is probably the best indication of a long remission.
Thank you Jackie. An important subject and no harm in reinforcing Oz's post.
Yours prompted me to revisit George Follows on youtube (he is a good speaker). In a video interview at ASH 2019 he mentioned a novel drug mosunetuzumab: a bi-specific antibody, which "grabs the T-cells and B-cells, brings them together, and triggers the immune system to attack the cancer directly... Manipulating our immune system, which is of course what we're doing with CAR-T cells, is really showing important promise" in a phase 1/ 1b trial in relapsed B-cell lymphomas. youtube.com/watch?v=0L3zIYh...
More recent info on bi-specific antibodies and their synergy with BTK inibitors adds to the early promise, and at least one trial is recruiting CLL patients.
I can see that the bi-specifics would be especially synergistic with BTKIs as they assist in improving T cell function. There’s so much good stuff coming along, lots of reasons to be optimistic 😊
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