Reaction to Venetoclax?

[keikikumu]

Aloha all. My husband was diagnosed with CLL in 2003 at age 53. He was on W&W until he started Acalabrutinib in January 2022. His WBC went down almost immediately. All was well until it wasn't. His WBC started to climb into "dangerous territory" in July 2022, so he then began infusions of Obinutuzumab this past December 2022; his WBC dropped back into normal territory and we rejoiced! That was going fine, no real side effects from the infusions except slight fatigue on the day of the infusions. By the time he was started on Venetoclax (still continuing with the infusions) in late December, his WBC had dropped such that TLS was not an issue for him at all. He continued both infusions and Venetoclax until Venetoclax had to be suspended for about 3 weeks when he tested positive for Covid at the end of December. He continued infusions, however. He was re-started on Venetoclax in mid-January again, eventually ramping up to 400mg/day. After about a month at the full dosage, he began experiencing fevers and cough and some weight loss. His oncologist was informed, and said to stop the Venetoclax to see what effect that would have. He's been off the Venetoclax for 5 days now and although his cough has diminished somewhat (still irritating if he talks too much), but the low grade fevers (99's, occasional 100*) and much increased fatigue are continuing. Oncologist mentioned stopping Venetoclax altogether and trying...."something else." We are wondering if anyone else has had a similar experience? Thanks in advance for any input!

[AussieNeil Administrator]

Hi Keikikumu,

I'm guessing you live in Hawaii, where there isn't good support for those with CLL? Irrespective, you really do need a haematologist or at least a haematologist/oncologist who looks after lots of people with CLL and keeps across the rapid changes in CLL management to provide your husband with the best care.

You haven't provided enough information for some particularly helpful guidance. There are 5 different white blood cell types that make up the total WBC count and the two that are specifically used to provide guidance in situations such as this are the lymphocyte count (which you want to drive low, because this includes the CLL cells along with healthy B, T and other lymphocytes) and the neutrophil count, which you want to stay high, because when it drops under 1.5 (that is he has neutropenia) the risk of infection increases.

I'd appreciate lankisterguy adding more to my reply, but in my opinion, your husband's oncologist should be looking into whether your husband has an infection, possibly fungal or whether his symptoms are a reaction to the venetoclax. Your husband's oncologist is following the official recommendation if your husband has neutropenia, venclexta.com/ but some specialists do use G-CSF injections to boost neutrophil production so that the patient is no longer neutropenic. If your husband's cough is productive enough to provide a phlegm sample, a culture can be done to check for infectious causes for his cough.

Neil

[keikikumu in reply to AussieNeil]

Aloha Neil, and yes, we are in Honolulu. John's oncologist is a hemotologist/oncologist and seems to be up to date, in our opinion, on emerging treatments for CLL. John's WBC count at the last test was 3.73, and was comprised of lymphocytes at 1.33, neutrophils at 1.64, monocytes at 0.74 and no eosinophils or basophils. After discontinuing the Venetoclax, the cough, which was never productive, has mostly subsided. Other than that, the only other remarkable blood statistic shows a low hemoglobin of 12.6 and a low hematocrit of 39.6%. He continues to have fevers in the 99. range every day even after taking Tylenol, and has a pretty good amount of fatigue as well. Just not understanding why he has even a slight elevated temperature on a regular basis, but he will be reporting that to his oncologist (again) prior to his next infusion, next week on April 20th. We will ask about a possible fungal infection. We are very appreciative of your input!

[AussieNeil Administrator in reply to keikikumu]

I agree that your husband's specialist is keeping up with recent CLL treatment options; my concern was whether they had the experience to know how to handle unusual cases, such as your husband's. The venetoclax looks to be working well based on your husband's lymphocyte count and his neutrophil count, while low (stage 1 neutropenia) is not of particular concern. So it comes down to what's causing the fevers and weight loss. I assume your husband has a good appetite, is eating his usual amount of food and isn't particularly affected by gastrointestinal upsets, which are not uncommon with venetoclax? Fatigue is commonly experienced during treatment (particularly after obinutuzumab infusions) and can persist after treatment ceases, so it's more a matter of how much this has worsened recently. Long-COVID may also need to be considered. Maybe all that's required for your husband, is a drop back in his venetoclax dose, which is not unusual, particularly given his CLL burden (nodes, spleen, bone marrow) should be quite low by now. His haemoglobin and hematocrit would not be out of the ordinary during treatment.

Neil

[keikikumu in reply to AussieNeil]

Thank you very much, Neil. We did look into possible infections - we made a trip to the emergency room once a couple of weeks ago when his temperature hit 101.9 (and 102 another night), and was screened for lung, urine and blood markers, but nothing showed up. His temperatures now seem to be settling into the 99* range. He has an appointment with his oncologist next week, and will definitely ask about a possible drop down in the venetoclax dosage, and/or feel out whatever else the doctor may suggest. Appreciate your prompt input!

[lankisterguy Volunteer]

Hi keikikumu,

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Neither AussieNeil or I have any medical training, but with the problems you are describing this may require much more than even a good general hematologist / oncologist.

cllsociety.org/2020/03/ash-...

Since with CLL we have compromised immune systems we can get some rare infections only seen by HIV-AIDs patients, and it make take an infectious disease specialist to test for the unusual possibilities.

Mention of a dry unproductive cough might prompt testing for a lung fungus or virus,

(Pneumocystis, Aspergillus, Histoplasmosis and Cryptococcus are examples that would not be considered by doctors accustomed to treating patients with normal immune systems)

and as you mentioned long COVID also could be considered, along with numerous other possible causes.

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Since you are in Hawaii, and we understand there are no expert CLL doctors there, you may want to request a free 2nd opinion by video conference with a CLL expert by applying to this program:

cllsociety.org/programs-and...

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We have some other members that might have suggestions where to find additional diagnostic or infectious disease help to add to your husband's medical team Hilomom and Cfarrar

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Len

[keikikumu in reply to lankisterguy]

Thank you so much. All good ideas. His oncologist did actually bring up seeing a pulmonologist to rule out any lung involvement. I think we will pursue that avenue next. This is an amazing group of helpful folks here; so glad I've found you.

[roszika]

It may not be the veneteclax -considering that your hubbie caught covid I think his reaction may be connected to a long covid post reaction not necessarily veneteclax -ask the oncologist if he has considered this-I was on veneteclax for 2 years -no problems and I know most people have not have such a bad reaction-I think it may be a coincidence and it would be a shame to stop the V as it generally leads to long remission but I am only a retired pharmacist so it’s just my instinct that is suggesting this

[keikikumu in reply to roszika]

Thank you so much. We've considered long Covid, but he had a good period of health post Covid before this cough and fatigue started. I would have thought that he wouldn't have felt fine after Covid, which he did, if it were long Covid. This is why we thought it could be the Venetoclax. Now I'm wondering if he should see a pulmonologist, which was actually suggested by his oncologist. Appreciate your reply!

[roszika in reply to keikikumu]

HiYou may be right but sometimes long covid can happen after what seems like a recovery- I doubt if its the Veneteclax-My specialist is the top CLLguy in Australia and even he would shrug his shoulders- the point is even the top guys don't know if it is the V or something else is happening to your husband because there is not enough post data info about these drugs like Venetelax- it is still a relatively new drug so by all means go to the lung specialist but it could very well be that Veneteclax is not the villain here

[Hermance]

I'm on Venetoclax also. During the ramp-up I got a bad reaction when I reached 200 mg. My dose is now 50 mg and I'm not going any higher.

[Poodle2]

I had a fever after my first O infusion - a reaction to the infusion. In week 2 of treatment, my fever was a sign of neutropenic sepsis but they didn't find the source of the infection. I also had a fever after each V dose increase which meant weekly A&E trips for further investigations. This lasted about 2 months, once I was on a full dose, things calmed down.

[Toast-up]

Hi Keikikumu,

As your post said any input might be useful, I thought I would just highlight a study done a couple of years ago that I had bookmarked. It is called "Acute Immune Signatures and Their Legacies in Severe Acute Respiratory Syndrome Coronavirus-2 Infected Cancer Patients ".

Th study basically looks at the difference between the effect on the the immune system between solid tumour cancer patients and haematological cancer patients when exposed to Covid. It concludes that "Thus, while solid cancer patients, including those with advanced disease, seem no more at risk of SARS-CoV-2-associated immune dysregulation than the general population, hematological cancer patients show complex immunological consequences of SARS-CoV-2 exposure that might usefully inform their care."

In other words Covid can have a lasting and significant effect on one's immune system that goes unseen. This may be a possible explanation why your husband is experiencing what, at first reading, seems to be immune system related problems that he wasn't experiencing before having Covid.

I probably ought to apologise in advance if I have got myself into a muddle with my understanding of the paper. I hope one of the administrators will pull me up if I am wrong. I am really not that bright at the moment!

[keikikumu in reply to Toast-up]

Aloha, Toast-up. Don't apologize. Any input or sharing of something you read is helpful, I've found. My husband's oncologist actually did mention the possibility of long Covid, but I would think there would be some sort of follow-up if that was his thinking. My husband's Covid bout certainly adds some possibilities to what is going on, and we aren't giving up! Thank you for your input, very much appreciated!

[Palmetto]

I may be coming from left field but low grade fever and unexplainable weight loss may be signs of a secondary cancer.

[keikikumu in reply to Palmetto]

Thank you, Palmetto. We have definitely thought of a secondary cancer as a possible "culprit" of his fevers and fatigue. Waiting to hear back from his oncologist (who, by the way, mentioned going to a pulmonologist a couple of weeks ago). We'd like to rule that out by doing that and hope to get a referral today from his oncologist. (But you know how that goes - they are "busy people" and sometimes we wait, and wait ). Really appreciate your input.