Brukinsa side effects.

[davidgrush]

Why is one side effect of Brukinsa an INCREASED risk of infections? (specifically upper respiratory). Has anyone had this happen?

[AussieNeil Partner Administrator]

All CLL treatments come with the risk of neutropenia and neutrophils are our first responders to prevent infections. Also all approved CLL treatments to date unfortunately also kill healthy B cells. The lack of naive B cells is why it's very difficult to for our bodies to produce new antibodies in response to infections or vaccinations.

I had a lung infection and pleurisy early after starting on acalabrutinib/Calquence, a very similar BTKi to Brukinsa/zanubrutinib. Infections are reasonably common, so keep an eye out for signs of infection and seek prompt medical attention accordingly, particularly if you are neutropenic.

Neil

[davidgrush in reply to AussieNeil]

Thanks Neil. I had been wondering if BTKi meds kill healthy B cells.

[mrgreentea in reply to AussieNeil]

Neil,

What about IgA levels? While neutrophils could be in the normal range, if IgA (which, for others, helps respiratory immunity) is well below normal, doesn't this also open one to infections?

Getting back to the original question, do you know if a BTKi changes the effectiveness of IgA plasma cells? (For me, Z doesn't seem to have changed my IgA levels - they were already low at first detection).

Separately, any idea how common is it to have your IgA/M/G tested? I know someone else (with WM) and doesn't recall ever having that test.

[AussieNeil Partner Administrator in reply to mrgreentea]

Overall IgA/M/G levels change slowly, so I gather are typically only tested every several years or so, unless we are on Immunoglobulin replacement therapy (IVIG, subcutaneous IgG), when our specialist wants to ensure that we are maintaining sufficiently protective IgG levels. IgA is important in protecting our membranes not only in our respiratory system but in our gut and urogenital system as well our skin, though skin cells can independently make immunoglobulins. Obviously it's best if we have sufficient IgA to neutralise any pathogens before they can cause infection. IgG replacement therapy works fairly well at supplementing for lack of IgA.

CLL has a dampening effect on plasma cell production of immunoglobulins, so reducing the CLL tumor load should improve immunoglobulin levels. During treatment, that's unfortunately countered by the reduction in B cells that would otherwise mature into plasma cells. The good news is that some members have reported higher immunoglobulin counts after targeted therapy treatments. If only we knew why!

Neil

[scryer99 in reply to mrgreentea]

My IgA has dropped below range in late W&W + 2 years treatment with zanubrutinib / Brukinsa (plus an experimental BCL2 inhibitor similar to venetoclax). IgG and IgM levels have been right at the bottom of normal range. Neutrophils slowly declining, just below range, not zero. Declines have been slow but steady. Immunogammaglobulin testing and CBC workups are a routine part of my clinical trial so I have frequent data points.

I've noticed that my immune system appears to be on the decline over that time period. Last six months I've been sick more often than not, with various illnesses in the upper respiratory realm. Severity has been worse than usual and recovery times greatly lengthened. It has not been fun.

I am a reasonably cautious CLLer, N95 masking indoors outside my home, avoiding large crowds, no air travel or face to face work. Still, I've gotten sick a lot lately.

My own interpretation of all this: the ongoing treatment + CLL presence has degraded my immune system somewhat. Note I have a relatively aggressive "plain vanilla" CLL presentation - fast, but normal genetics. The BCL2 inhibitor I'm on (sonrotoclax) is quite potent as well. So some things that could stress my immunity.

I'm likely exiting treatment sometime this year -- I'm already past the trial end date but sticking with it in the hopes of achieving uMRD. My hope is that being relatively cancer-free and off the meds will give my system a chance to recover.

As far as coping, my standard routine, developed with my oncology team, is to give a new illness a couple of days to show it's for real, then go and get a full respiratory panel workup (nasal swabs and a couple days lab work). This ensures I know what I'm dealing with and whether it's HMPV (viral, just deal with it), OC-43 (coronavirus, just deal with it), bacterial infection (antibiotics), or more serious types of pneumonia (watch carefully and head to the ER if needed). Other than that, just soldier on. I've also noticed I need more bedrest to recover from these.

Look at it like a game - so far I'm 5 for 19 on my respiratory panel card! Bingo!

[mrgreentea in reply to scryer99]

I really appreciate this info on testing. I think we MUST instruct the med staff we see on what (we hope) they do so that they don't end up delaying a time critical diagnosis.

In particular, I've heard that pneumonia has a tendency to scar/damage tissue which will lead to bigger issues, so we definitely need to catch it asap.

I tend to have sinus issues more than anything else right now. I was just in & they only checked for flu, said I didn't have it, and then sent me home without any treatment plan. A week later I'm feeling somewhat better. I'll try to suggest your list of tests next time.

The issue I am seeing is that there seems to be no specific cause or treatment for feeling crappy / head fog - so we must just endure until it subsides. At some point the medical field will better understand it & hopefully have effective treatments. I'm ecstatic however that they focused on CLL first

[Red49]

I’m on Brukinsa since November 2024, neutrophils are all in normal range, WBC and ALC are close to normal. Having said all this I caught an upper respiratory infection in February I didn’t leave my home for four weeks. Three weeks from couch to bed, five weeks with a productive cough.

Unfortunately I was well into it before I found out I could have been tested for RSV or Influenza. I did get a puffer to help open up my airways.

[mickimauser11]

They gave me Cotrim 3 x weekly which is supposed to protect against lung infection

[Sandywhatsit]

I have been taking Brukinsa since January this year (previously in remission with Venetoclax for 3.5 years). Blood tests this week show that it is working. I have been offered prophylactic antibiotics and antifungals but have not taken this up so far - I had a virus before Christmas that took a while to throw off but otherwise I've kept well. If this changes then I will think again.

[CoachVera55]

Hello David, I am the Poster Child for Infection with Zanubrutinib. I believe its a risk is because Zanu goes hard on the immune system. I had a enlarged cervical node on my Trapezium muscle that was very noticeable to me for about 8yrs, well it disappeared in 3-5 days.

I continued to workout vigorously & developed sustained Chest Pain on the 13th day of Full Dose of Zanubrutinib. I went to the Emergency Room & my EKG showed runs of PVC’s showing my heart was irritated. I was fast paced in the triage & placed on a monitor. All Labs, Xrays, sequential EKGs & Echocardiogram were normal. However my CTA Scan showed Pleurisy - Bilateral Subsegmental Dependent Aetelectasis. Of those words I knew Aetelectasis meant ‘COLLAPSE’ goggle it if you don’t believe me. Everyone swore ‘My Lungs were not Collapsing’ I had an appt with My Oncologist the next morning so I allowed them to discharge me.

I seen my lazy Oncologist the next day & the chestpain that dropped to 2/10 was now back & up to 8/10. I am holding my chest when I see him & he could care less. He asked me if I was sure it was my chest & not my stomach. All I got was for him to order Acalabrutinib because I wanted no parts of Zanubrutinib.

I leave his office & the whole hospital & get an emergency appt to see my PMD & Pulmonologist & I just knew I’d be safe now. Nope he refused my direct request for Steroids & Antibiotics, even with my CT Scan Report in his hands & said to see my Oncologist. I decompensated in his office after 48hrs of chest, I needed his oxygen & wheelchair. He only offered me Tylenol #3. I told him that I had Tramadol at home but what I needed was to be able to breathe. He notified me that he had disconnected my oxygen & that my pulse oximetry numbers never dropped under 97% although I am rubbing my chest because it was burning & using every accessory muscle to breathe. He urged me that I was frightened my 28yr old son. He escorted me out to make sure he got his oxygen tank & wheelchair back. He was my doctor for 30yrs

My son gets me home & has the sense to put me on a nebulizer machine & then ask where to Mom. I said son call 911 because I don’t want to die in your car. Long story short I get back to the same Emergency Room I left 48hrs earlier & this CT Scan shows Pleural Effusion, Pneumonia vs Aetelectasis. Every Chest Xray & EKG is showing signs of a worsening condition. I get treated with steroids but still no antibiotics.

I see this Northwell Pulmonologist & he says it looks like you had Pneumonia & did you get antibiotics. I honestly said that I used some old antibiotics during the same time I was on the steroids but that I need antibiotics. He said that he did not feel comfortable ordering antibiotics but that he would order steroids. He ordered a repeat CT Scan & Pulmonology Function tests. I did the CT Scan 1 month after seeing him so 6 weeks after the initial Chest Pain, Pleurisy/Pneumonia/Pleural Effusion issue. That CT Scan says Parencymal Scarring & the PFTs says Moderate Chest Restriction

2 weeks after that so now close to 3 months I get sustained Chest Pain & back to the Emergency Room. This 4th CT Scan in 3 months shows ‘Normal’. The ER Doctor sees my chest so rigid & orders Muscle Relaxants. I was on 1/2 dose of Acalabrutinib but it felt like a 5lb weight was on my chest & I was feeling Palpitations. I got Cardio to order another Echocardiogram & even a 72hr Holter Monitor but no one would order antibiotics.

I begged my 2nd Oncologist for antibiotics after I finally seen the previous CT Scan & PFTs. I’m in the middle of putting all the information together & she is looking at me as if I am something on the bottom of her shoe. I literally have a Panic Attack, I can’t breathe in my mask, the tears are flowing like waterfall & the walls are closing in on me & I am screaming in disbelief ’Y’all are really trying to kill me’. I come off the exam table & the sorry ass doctor holds on to wall thinking today is the day she will meet her Maker. But I am heading for the sink to try & compose myself. I leave after drying off with my hands in front of me to guide me out because I simply have no more words. I tried to see other doctors before this but they asked me why didn’t they treat me & want to start over with more radiation diagnostics & I’m done with it all.

I get my Classmate to get antibiotics for me from her doctor saying that I am her undocumented worker, meanwhile I have Federal Aetna with $1200 per month premiums. I get the 10’day dose of antibiotics & then I start to improve. I then get connected with my CLL Specialist & things go better.

I was down to 1/4 dose of Zanubrutinib when the 1/2 dose of Acalabrutinib was causing Chest Pressure & Palpitations. I stopped cold turkey & went into vicious withdrawls called Rigors on day 4. That’s when I went to 1/4 of Zanu, 80mg daily & it maintained me with slow progress. My CLL Specialist got me examined by her Cardiologist & Pulmonologist. When they thought I was healed we went up to 1/2 dose of ZANU 80mg Twice daily & in 1 weak I got Flu like symptoms. This time I was treated promptly & everything went smooth.

For me I need to be treated Promptly, Properly & even Prophylactically with the first sign of infection. Nip it in the bud & things go great with Zanubrutinib. I love this drug & since I had a 13yr 8m Wait & Watch this might be my all time drug 🤷🏽‍♀️ I know its long but you did ask lol

[mrgreentea in reply to CoachVera55]

It's painful to read all of this. It's really unfortunate! Might be worth going to a video doc next time (if you can) & claim symptoms that would align with a need for antibiotics... like a sinus infection. Maybe?

[CoachVera55 in reply to mrgreentea]

They had 4 CT Scans in 3 months all showing worsening of my condition, Echocardiogram & Holter Monitors too. They ran up my good insurance & still refused to treat me properly. I am filing charges on them individually & trying to sue all of them connected because someone else less blessed would of died!

I have a CLL Specialist & am stable now so this is the time. Whenever they don’t do their jobs I file charges with the Patient Relations & create a Paper Trail. I keep a stash of antibiotics but I wasn’t even sick for 13 months. I wear a mask everywhere, stay out of crowds & use Natural Herbal Chemotherapy!

I have always been advocating for my patients nearing 30yrs at the bedside, HomeCare & School Nursing so I have plenty experience in this arena. I was just too weak & that’s what cowards wait for. My last full time RN position was at the Brooklyn VAMC, you don’t spend time with soldiers without becoming like them 💣