I’m 55 and on my fourth line of treatment in 4 years: BR, Ibrutinib, Venetoclax, Acalabrutinib. And it looks like I’ll need a fifth soon.
The acalabrutinib keeps the CLL in check but gives me neutropenia.
Stopping acalacbrutinib for a week raised my ANC from 0.6 to 2.0. Lymph nodes grew quickly when I was off the medication. For example a node in my neck went from non palpable to a 4 cm plainly visible bump in a week.
After a few more weeks my ANC trended downward to 1.0. This time we tried 5 days of GCSF. A week after the 1.0 reading my ANC was 3.5. Two weeks later, today, I’m at 0.3. And scared.
I haven’t spoken to my doctor yet but I’m thinking I should stop the medication for a few days and then try a half dose.
I think it is very likely I’ll need to try yet another treatment. What are some other treatments? Most all treatments have given me neutropenia.
My second opinion doctor said, before I started acalabrutinib, that I was running out of effective treatments (I try not to replay his words in my head) and mentioned car-t. I asked him how car-t was going. He said initial results looked promising but not so much now or something depressing like that.
My primary oncologists said I would eventually need a BMT (I don’t have a sibling donor) because I would run through treatments faster than they are invented. But first he’d try some other pills including some “boxed warning” ones.
So I’m here to tap into the collected wisdom of the great people of this forum.
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john-doe
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try to get on a loxo 305 trial. it seems to work well for even people who are on 4th and 5th line however based on what you say the issues aren/t drug effectiveness but the neutropenia side effect
LOXO-305 is one of many new BTK inhibitor drugs currently on trial. See: healthunlocked.com/cllsuppo... , in which in one of my later replies, I report most of the current and in trial CLL treatments. What makes LOXO-305 different from many of the other BTKi drugs, is that it reversibly bonds with the BTK enzyme in CLL cells, rather than permanently bonding (in other words, it bonds non-covalently rather than covalently).
Unfortunately neutropenia is a common side effect from CLL medications, so I'm not sure whether switching to another BTKi will help you, as you may continue to exhibit neutropenia. You haven't mentioned treatment with a PI3-K inhibitor, such as Idelalisib. (Idelalisib is approved for second and subsequent treatments in a few countries after trial experience found that the side effect profile was higher in first line treatment than subsequent lines of treatment). There are also a trial available second generation PI3-K inhibitors Duvelisib (also known as IPI-145), Umbralisib (development codes RP5264 and TGR 1202) and ACP-319 (also known as AMG-319), plus BP1002, a competitor to Venetoclax (but I don't know if that has a better neutropenia profile than Venetoclax, which has a reputation for causing neutropenia).
With most CLL treatments, the approach to managing neutropenia is using G-CSF injections, but certainly with Ibrutinib, the approach is to temporarily cease or modify the drug dosage. Some of us are on half dose Acalabrutinib (one tablet daily), which may work for you, although I can appreciate your concern that a half dose will keep your CLL under control, given your scary experience when you temporarily stopped. Given your unusual circumstances along with the fact that you live in the USA, I recommend that you try and arrange a free second opinion with a recognised CLL specialist through the CLL Society's Expert Access program: cllsociety.org/cll-society-... I wonder if a viable approach will be to stay on Acalabrutinib with the support of G-CSF? That was the approach that worked for me on the Acalabrutinib+Venetoclax+Obinutuzumab trial.
My CLL specialist has worked with CAR-T patients. The impression he has given me is that it has a lot of risks, but it is a risk to take if it is the only path remaining. Not sure that helps...
Mostly I wanted to say I read your post and am hearing/feeling your situation. I hope you find the information you need to restore your health. We are here for you!
john-doe, I am in a Loxo-305 trial. This is my 4th treatment, FCR, imbuvica, venclaxta, over an 11 year period. It is working very well for me and my blood counts are normal. I too had some early problems with my anc, down to .8, but with a few booster shots six months ago now at 2.2. Only problem is with my platelets, 105, but these have been low for 12 years. So far no side effects. I just started cycle #12. There are more locations available in the US now than there were when I started last Jan.
I am a strong believer in extra nutrition, since the cancer cells eat up a lot of nutrients and stress depletes B vitamins. If its OK with your Dr (no kidney problems, gout, etc) increase your protein intake and nutrients like asparagus to make sure you have enough of everything on board to make neutrophils. I buy egg white protein powder to make smoothies, add to cooked oatmeal, etc. instead of trying to eat whole foods--my enlarged spleen means I need a smaller volume of concentrated nutrition since I can't eat much at one time. I weigh about 118 lbs and eat 50+ grams complete (not partial like peanuts) protein daily. A food could be considered "high protein" but we need all 7 essential amino acids in the correct proportion. So If I want peanuts, I have some milk & bread along with, or make a peanut butter sandwich, since they complete the amino acids. The only nutrients I don't take above the RDA are the fat soluble vitamins A & E.
I am best friends with anxiety. I do worry that my anxiety puts an added strain on my body and immune system which is basically saying I am anxious about being anxious. I have started talk therapy and meditation. It makes sense that food can help too.
I too eat a lot of small meals. Do rice and beans have all 7 essential amino acids? I’m a big fan of r&b.
Rice and beans is one of the classic "protein complementary" combinations. Beans tend to be deficient in tryptophan and the sulfur containing amino acids and high in isoleucine and lysine, while the reverse is true for rice. So together, you get a boost in the total amount of amino acids available. The classic book on this IMO is Frances Moore Lappé's Diet for a Small Planet. The book has recipes, charts, and discusses how a meat based diet and consumer advertising affects us & the planet. This is where I came up with the idea of extra protein in my CLL; she discussed how Special Needs like pregnant women need about a 60-70% increase in protein. She heavily referenced and indexed, this is not some fad dietary advice. She researched all this. So when I was diagnosed, I figured the cancer was a stressor sucking out my body's nutrients & I needed extra to maintain a semblance of normal homeostasis. And it appears to work for me. Except when under heavy immunosuppresive treatment, I manage to keep my basic blood components somewhat stable (I.e. my platelets are low at 100....but they pretty much stay there unless poor diet/heavy treatment) if not actually low normal. And my labs reflect when I am not eating optimally for sure. Neutrophils 1.5? I start pushing asparagus & other neutrophil micronutrient foods & they creep up to 1.7. Low RBC/HCT? Oh, didn't eat meat or take an iron supplement at all last week. I am NOT saying that diet can cure any blood component derangement, just that it definitely can affect it. Everyone is different & to what extent nutrition affects their disease course will be different..... but why not give your body the best chance it can have with optimum nutrition?
Yes, my second opinion doctor mentioned car-t (sounded like he meant soon). My primary oncologist who is covered by my insurance said bmt (sounded like he meant after trying every FDA approved pill).
I tried one 5 day course of gcsf. But a couple of weeks later (ie yesterday) my anc crashed. Maybe the injections should be spaced out?
Second opinion doctor, a recognized CLL expert, suggested trying dose reduction if the neutropenia happens again, which yesterday’s lab (anc 0.3) confirmed it did.
I wrote to both primary and secondary doctors yesterday but have not heard from either. I’m surprised my primary doctors office did not contact me given how low my anc is.
So I took matters into my own hands and skipped last night’s dose. And I guess I’ll skip this morning’s dose. But want to restart very soon.
It is so nice when labs go well and I can sort of forget about things until next labs.
It is concerning when you must take action that contrasts your specialist's directives, however, given what you have written here I understand the level of concern you must have.
I would definitely contact the cllsociety as Neil suggested. As you most likely already know Dr. Koffman has a history of treatment relapse also, and he is a Car-T pioneer.
We all share your urgency and concern and. We hope you can move quickly with this to achieve the desired results that you need.
You need to be aware of two very important factors with respect to neutropenia:
1) Neutrophils have a very short half life in the blood - from hours to days according to the study method used to measure this
2) If your bone marrow totally stops making neutrophils, it takes 10 days from when your bone marrow restarts until neutrophils begin to appear in your blood
That means it can take quite a while for the impact of any medication changes and G-CSF injections to show in your blood tests. Until treatment, I had chronic, severe neutropenia throughout my 11 years of watch and wait. At one stage after my neutrophils crashed, I required daily G-CSF injections for 3 weeks before my ANC crept above 1.5. When treatment began to clear out my bone marrow, I was at last capable of dramatically responding to one G-CSF injection within a day or two. I haven't needed a G-CSF shot for over 6 months and I'm still on full doses of Acalabrutinib+Venetoclax.
The two tools I have to help me stay on Acalabrutinib are dose reduction and gcsf. I need to figure out a good combination of the two.
I did not know that neutrophils were so short lived. That is useful info. And seems to match with my experience. Five days of giving myself gcsf shots gave me an ANC of 3.5. Those are rock star numbers! But 2 weeks later and I am now at 0.3.
I’m wondering if it would help to space out the gcsf injections and stay on them for a longer time. Perhaps every second day or every third. The injects did enlarge my spleen when I did 5 in a row.
I needed G-CSF injections anywhere from daily to several times a week for the 18 months I was on them prior to starting treatment, about injections 200 all told. My specialist adjusted my G-CSF injection frequency based on how well I was responding to them. When I was having weekly blood tests during my diagnosis, I saw my neutrophil count drop by half every weekly blood test, down to 0.4.
The half-life of Acalabrutinib is only a matter of hours - shorter than Ibrutinib's which is why the recommendation to take it twice a day, rather than once daily with Ibrutinib. It's a pity that Acalabrutinib is not available in a half dose.
Don't dismiss CAR T as an option if you can get it. It is presently only available for CLL in clinical trials. I failed FCR, ibrutinib, and venetoclax, but then was accepted into a CAR T trial. I had a complete response and, after 15 months, there is still no sign of CLL. Yes, there are side effects that can be serious and you will probably spend some time in the hospital, but the science is moving fast and the doctors are learning how to control the side effects. Although the initial trials with CAR T in CLL were disappointing (25% response) recent trials have done much better as shown in the slides below from a presentation at the ASH conference last weekend.
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