Venetoclax and high total bilirubin?

[Dendi]

Hello,

I have been reading your posts for the last several months and the time has come to me to write a post as well.

My father, 64 years old, has been diagnosed with Cll/Sll. It all started accidentally a year ago after blood test which showed his Hgb level was low: 10,4 and WBC was high. At first the doctors decided to W&W. There was a marrowbone biopsy made in the end of January which resulted at CLL, with suspicion of second illness- mielophybrosis. It was quite a shock for all of us, even more because the doctor was not certain about what was going on and as described it, it was pretty unusual case. However in March his platelets dropped, Hgb was 8,6 and doctors decided to start with Endoxan. We are based in Bulgaria. He had two courses of it within 3 months, because of COVID in April, which deteriorated his blood results even more. Endoxan resulted in decreasing his spleen with 4-5 cm, and since the middle of June my father started ramping up with Venetoclax. When he reached 400 mg Rituximab was included as well once per month. Up to this moment he has had 5 courses of it, because in August his bilirubin and ASL started to raise and there doctors decided to miss Rituximab that month until Hepatitis was excluded. From June to November Hgb varied from 10,5 to 9,6. November Venetoclax was lowered to 200 per day.

However this month his total bilirubin reached 40 ( the upper limit is 21) and Hgb was 8,6, the doctor explained to him that there was a hemolisys. After staying at hospital for 5 days and treatment, without Venetoclax last week TBil dropped to 30, and Hgb to 7,9. Since Friday he started V again - 200 mg per day. Doctors explained that if TBIL raises again this week (he will be checked on Wednesday) Venetoclax will be stopped for good.

I know it is a really long post. I will appreciate any opinion on this. Is there any one with same results after Venetoclax and can it be the culprit for this Hgb drop and Total Bilirubin raise.

Thank you and take care!

[AussieNeil Partner Administrator]

Hi Dendi,

One of the listed side effects of venetoclax is anaemia, but it is rare for it to be so severe as in your father's case. The high bilirubin result is from the rupture (haemolysis) of red blood cells, spilling the red blood cell contents into the blood serum*. Your father's doctors are taking the appropriate actions to see if venetoclax could be the cause of his severe anaemia and whether he can tolerate venetoclax at a lower dose, which should hopefully be sufficient to treat his CLL. We do have members doing well on a reduced venetoclax dose.

Incidentally, most of our community would better know Endoxan as cyclophosphamide, the 'C' in FC.

*From mayoclinic.org/tests-proced... *Bilirubin (bil-ih-ROO-bin) is a yellowish pigment that is made during the normal breakdown of red blood cells.

:

Occasionally, higher bilirubin levels may be caused by an increased rate of destruction of red blood cells (hemolysis).

Neil

[thb4747]

Just a thought. I’ve been taking Venetoclax since April 2018 (200mg daily since November 2018). The highest my bilirubin has reached during this period has been 22. Looking back over 20 years of blood results, the only time my bilirubin levels were high was during periods of Autoimmune Haemolytic Anaemia. I’d recommend asking your doctor to run a Coombs test to establish whether AIHA is causing the problem. I wish your father well.