high WBC count with Brukinsa

[1955Leilani]

My Partner’s white blood cell count has continued to grow since he started Brukinsa. The count has increased from around 25,000 to over 72,000. The doctor thinks this is fine. My partner and I do not. Has anyone had this experience or can explain this? The count increases from 5,000 to 10,000 every week! How can this be okay.

[AussieNeil Partner Administrator]

Relax, your partner's doctor is highly likely quite correct, provided your partner has been on Brukinsa for less that around 12 weeks or so. See the attached plots of how white cell counts changed for patients on a very similar BTKi. BTKi drugs work by releasing CLL cells from the nodes and marrow, so that they flood into the blood stream, boosting the lymphocyte count. I suspect your partner didn't see this when treated a year ago, because the IV treatment, presumably rituximab or obinutuzumab, quickly killed the CLL cells in his blood.

If it is any consolation, in the early days of the first BTKi (ibrutinib) clinical trials, some specialists also became very alarmed when they saw this happening and wanted to stop treatment.

Neil

Lymphocyte/WBC counts often peak for up to a few months before declining on BTKis

[1955Leilani in reply to AussieNeil]

Thanks for sharing this. My partner was first on Imbruvica then Calquence. This did not happen with those medications. On Calquence his WBC started dropping immediately and significantly!

[SofiaDeo in reply to 1955Leilani]

If there was a significant period of time between the Calquence therapy stopping, and the Brukinsa treatment starting, cells inside the lymph nodes and spleen can grow in that time period. You don't see changes in the blood, they are internal changes. The lymphocyte count appears stable since the CLL cells are growing preferentially in the nodes/spleen. That is the source of the cells now showing in the blood, as they are pushed out of those places.

You don't mention other significant labs that doctors generally monitor, which is likely a reason the doctor seems pleased. If other cell counts didn't move the desired way, and lymphocyte count continued to rise, I doubt the doc would be OK with that.

Not all of us see a rise before a drop, I didn't when starting on Imbruvica. There are even some reports/concerns about people on BTKi's with a high tumor load getting rapid CLL cell death more on the "venetoclax" treatment spectrum, instead of the usual "counts rise before they fall" BTKi spectrum. So some people do see a rapid decrease on Calquence and other BTKi's. Just because he responded one way to one BTKi does not mean he will respond the same way to another. Similar to how some of us have no side effects with certain cephalosporins, yet others can cause nausea, diarrhea, or other side effects.

[1955Leilani in reply to SofiaDeo]

Hi and thank you. This is new information about the build up in the lymph nodes and spleen. I’m curious to know why the medication is moving them into the blood stream. Do you know? This was very helpful. Thank you!

[1955Leilani in reply to 1955Leilani]

Them meaning cancer cells.

[AussieNeil Partner Administrator in reply to 1955Leilani]

BTKi drugs block the adhesion signalling through which CLL cells stay in their established nodal microenvironment, which provides a degree of protection against treatments. (CLL cells surround themselves with protective nurse and stromal cells in the nodes, spleen and bone marrow.) The CLL cells are thus more vulnerable in the blood stream and with stay alive signalling blocked by the BTKi drug, eventually undergo apoptosis and are recycled by our body. It's only what's in excess or can't be recycled which gets excreted, but it's important to drink enough fluids to flush those along with the breakdown products (metabolites) from the BTKi out of the body.

Neil

[AussieNeil Partner Administrator in reply to 1955Leilani]

If you look at the plots carefully, you'll see that the lymphocyte count for Patient 2 (light green) never increased and the lymphocyte count for several other patients only peaked in the first 1 to 3 weeks before going down. In the Imbruvica trials, only around two third of patients experienced an initial peak in their lymphocyte count before their counts began to fall.

Also, from what you shared previously about your partner, his treatment protocol probably prevented a peak from occurring. On April 2022, you posted that "He started on an IV medication and then Imbruvica which quickly brought his numbers down." As I said in my first reply, "I suspect your partner didn't see this (peak) when treated a year ago, because the IV treatment, presumably rituximab or obinutuzumab, quickly killed the CLL cells in his blood." Then on 12th October 2022, you posted "my partner went through initial treatment with Imbruvica then Calquence." Unless there was a break between switching from Imbruvica to Calquence, your partner's CLL tumour load in his nodes and spleen wouldn't have had a chance to increase so that a peak could happen.

It's certainly possible that your partner's CLL has developed resistance to covalent bonding BTKi drugs so he would need to switch to a non-covalent BTKi therapy (pirtobrutinib can be prescribed in the USA off-label) or another treatment drug (usually venetoclax). However, as SofiaDeo noted, "You don't mention other significant labs that doctors generally monitor, which is likely a reason the doctor seems pleased." These labs would be changes in haemoglobin, platelets and neutrophils. They can decrease a bit after starting treatment before improving. Further the lymphocyte blood count is just the easiest CLL tumour load parameter to monitor. Your partner's doctor presumably has checked for reductions in the size of your partner's nodes and spleen - which is where the lymphocyte peak comes from if it occurs. If your partner's nodes and spleen sizes are not improving, then your cause for concern is justified.

I hope the replies to your post have given you enough understanding to reassure you and your partner, or given you good reason to follow up with your partner's doctor.

Neil

[1955Leilani in reply to AussieNeil]

His red blood cell is on the low end of normal. Same with platelets. Thank you for giving me more info. I wasn’t aware of the build up in the nodes and spleen . There was a significant time between Calquence and brukinsa. Thank you!

[Silvafoxe]

I’m a bit late seeing this . I e been on Brukinsa about 5 months and was told to expect increase in WBC initially but to our surprise the count decreased. I hope by this time your partners WBC has decreased significantly.

[Charmn in reply to Silvafoxe]

I have been on Brukinsa for about 7 months now and did not see the expected rise in WBC levels. Oncologist told me that I probably would see rise. Did see expected increase in WBC after Bronchitis and treament with Prednisone. No decrease in approx. 3 to 4 weeks post treatment. Now scheduled for CT scan to see if shrinkage in lymph nodes and hopefully account for elevation in WBC.

[AussieNeil Partner Administrator in reply to Charmn]

There are five different main types of white blood cells included in your WBC count, so you need to look at the 'Differential' section of the report to determine what's really happening. See the discussion about this in this pinned post.

healthunlocked.com/cllsuppo...

Even within the lymphocyte count, there are two main types of T cells, helper and cytotoxic, plus there are healthy and cancerous - CLL B cells, along with some natural killer lymphocytes. All respond differently to infections and treatment.

If you look back at the plots of absolute lymphocyte count changes when treated with acalabrutinib in my earlier reply, healthunlocked.com/cllsuppo... you'll see that not everyone sees a rise in their lymphocyte count. Trial results with ibrutinib, found that about a third of the trial participants didn't have a rise in their absolute lymphocyte count.

Neil