how common is tumor lysis syndrome after infusions?

[elm1]

Im reading about cll infusion treatment. A side effect is tumor lysis syndrome. I'm wondering how common that is

[Poodle2]

I asked my CLL consultant the same question before I started O+V. I was treated at one of the biggest cancer hospitals in the UK so they must be seeing lots of patients. She told me they are so good at monitoring and spotting any clues to prevent it that she actually doesn't remember even one case of TLS in the hospital. That put my mind at ease. The blood draws and tests are as frequent as they need to be to spot any changes. As long as you drink the amount of water that is recommended and you have all your blood tests, personally I think the likelihood of having TLS is very low.

[elm1 in reply to Poodle2]

Thanks sooo much

[roszika]

Hi

TLS was a problem when Veneteclax was first introduce when it was administered on a high dose to start with and caused TLS because of the mass shedding of white cells but then it was realized if V is ramped up 20, to 50 to 100, to 200 to 400mg over 4 weeks TLS was no longer a problem so I would not worry plus you are monitored frequently so if there is any sign of TLS the medicos now know how to act upon it asap. Because it is ramped up I doubt it is a problem at all having been ramped up myself

[SeymourB]

elm1 -

TLS (Tumor Lysis Syndrome) is largely a theoretical problem now. TLS is caused by billions of CLL cells dying so quickly, the kidneys have trouble filtering the cell fragments. The doctors know who is at risk (high ALC, swollen nodes and spleen), and what to do to counter it - starting allopurinol several days before to lower the risk of uric acid, extra fluids orally and via IV, plus doing the dosage ramp-up for Venetoclax.

There's 2 types of TLS - Clinical and Laboratory. I experienced the Laboratory TLS on my first IV infusion of Obinutuzamab plus oral Pirtobrutinib on a trial at M.D. Anderson, in Houston. Some of my electrolytes were out of range. I can't say I've seen too many mentions of actual TLS in other patients on this forum.

The Clinical TLS is much more serious and even rarer - seizure and cardiac arrhythmia.

Fortunately, because I was at risk, they had decided to admit me before the infusion as a precaution. I do hear of that happening to others sometimes. So everyone was on hand with all they needed. As fate would have it, I also had an infusion reaction to the Obin. That's more common than TLS. Often they just need to pause the infusion, and restart slower. The subsequent infusions almost always go without a hitch.

=seymour=

References:

ncbi.nlm.nih.gov/pmc/articl...

Advanced Practice Perspectives on Preventing and Managing Tumor Lysis Syndrome and Neutropenia in Chronic Lymphocytic Leukemia

AdvancedPractitioner.com V o l 12 , No 1 , Jan/Feb 2021

ncbi.nlm.nih.gov/pmc/articl...

Cytokine release in patients with CLL treated with obinutuzumab and possible relationship with infusion-related reactions

Blood. 2015 Dec 10; 126(24): 2646–2649.

[elm1 in reply to SeymourB]

Thanks soo much. But now I’m worried about the reaction to O! Lol

[SeymourB in reply to elm1]

elm1 -

And you should be concerned. There's many comments here on infusion related reactions. I've never heard of someone dying from it or suffering lasting injury. It's not fun, though, and the hospitalization could be expensive in the U.S.

I have to say in retrospect (I finished treatment on February 13, 2024), I'm really glad I did the Obin. I think it was responsible for a great deal of my phenomenal numbers. I lament the effect on my immune system, though, and look forward to future anti-CD20 MABs that might have less effect on immune function.

One thing in the last year that has prevented infusion reactions is starting BTKi's or Venetoclax before anti-CD20 therapy. It's well documented with BTKi's, though few get anti-CD20's along with just a BTKi except in trials. There's only a few trials doing Venetoclax before Obin, as far as I'm aware. The general idea is that almost any other treatment that can debulk before Obin prevents the infusion reaction. It's ironic that Obin was touted as a debulking therapy before Venetoclax - as if Venetoclax is the big problem in that regard. The dosage ramp-up solved almost all of the problems with Venetoclax and TLS to the point that some trials are now doing a slightly accelerated Venetoclax ramp-up if an earlier BTKi is given.

I think in your case as in the U.S., your options are still limited to a BTKi forever vs Obin plus Ven vs fixed duration Ibrutinib plus Ven. Ibrutinib has a reputation for cardiac risks, however. They just haven't approved Acalabrutinib plus Ven or Zanubrutinib plus Ven yet (or Pritobrutinib and Ven, for that matter). You could try to access a trial to get combos.

If you've only recently been diagnosed, time is on your side! There's multiple fixed duration BTKi/BCL2 combos out there in trials that may get approved before you need treatment.

=seymour=

[elm1 in reply to SeymourB]

You are a wealth of info! I was diagnosed 6 years ago but my white count has significantly gone up in the last year that why my doctor wanted to prepare me for the fact that at some point I will need treatment. Going back in two months to see how fast this is progressing.

[elm1 in reply to SeymourB]

Do you think I should check out trials. I live in the Chicago area.

[SeymourB in reply to elm1]

elm1 -

Trials require a significant investment in time. I don't think you have to due to being extra risky from what I've seen (you're 13q with mutated IGHV, right?) A trial might offer a longer remission or not, depending on how the trial is organized in regard to cohorts or arms. Trials give excellent testing and review by experts, which could be important if you have anything unusual in your CLL or comorbidities.

=seymour=

[elm1 in reply to SeymourB]

Thanks.

[Poodle2 in reply to elm1]

Please don't be worried. Read as many posts as you can about people's experiences with O. A vast majority have a reaction but it doesn't have to be anything dramatic. I wrote about my experience - like many others. Read as much as you can. Prepare yourself that it is likely you will react. The chemo ward teams are very experienced, they usually stop the drip. Give you more medication to help and start at a slower pace. After that it is usually a smooth sailing. With the team on board, the reactions might be unpleasant and a bit scary but I have not read/heard that anyone would die as a result of it.

[elm1 in reply to Poodle2]

Good to know. I really don’t want to die.lol what are the typical reactions

[AussieNeil Partner Administrator in reply to elm1]

The Gazyva/obinutuzumab healthcare professional site notes this with respect to Infusion-Related Reactions (IRRs) in the First-Line CLL information;

"Sixty-five percent of patients with CLL experienced a reaction to the first 1,000 mg of GAZYVA infused. Thirty-seven percent of patients with relapsed or refractory NHL and 60% of patients with previously untreated NHL experienced a reaction on Day 1 of GAZYVA infusion. IRRs have occurred within 24 hours of receiving GAZYVA. IRRs can also occur with subsequent infusions. Symptoms may include hypotension, tachycardia, dyspnea, and respiratory symptoms (e.g., bronchospasm, larynx and throat irritation, wheezing, and laryngeal edema). The most frequently reported symptoms include nausea, fatigue, chest discomfort, dyspnea, dizziness, vomiting, diarrhea, rash, hypertension, hypotension, flushing, headache, pyrexia, and chills."

So basically, the advice is to inform the infusion nursing staff immediately you feel anything unusual, so that they can promptly manage it.

The first 1,000mg is split into two infusions, given on subsequent days, with a 100mg test infusion given on the first day, then the remaining 900mg on the second day.

On my acalabrutinib + obinutuzumab + venetoclax clinical trial, I developed violent uncontrolled leg spasms half way through the my first 100mg Gazyva infusion, just after the nurse took my observations. It came on suddenly, as is common for obinutuzumab compared to the older rituximab anti-CD20 monoclonal antibody infusions also used for treating CLL. The remaining 8 infusions passed without incident and were just tedious - it takes about 5 hours or more for an infusion, depending on how well the nurses are able to ramp up the infusion speed. (You need to wait an hour for the pre-meds to take effect) There's a huge amount of experience using these drugs for CLL treatment; rituximab has been used for over two decades and obinutuzumab for about a decade.

Commencing my CLL treatment was delayed 2 months for reasons out of my control, so my health rapidly deteriorated when I started treatment, mainly because my bone marrow had run out of capacity. My recovery commenced with that first obinutuzumab infusion. Ironically, I was so ill by then, running a very high temperature, that the clinical trial staff first delayed my first obinutuzumab infusion by four days, then had to check with the overseas clinical trial management whether they should proceed with the infusion or drop me out of the trial. That was 4 years ago and my blood counts are better now than they were back in 2006 - a few years before I was eventually diagnosed with CLL.

Of note; I was a candidate for TLS prior to starting treatment, because I had a very enlarged spleen. In my clinical trial protocol, the CLL tumour is debulked by a month of acalabrutinib, then a combined month of acalabrutinib and Gazyva infusions before the venetoclax ramp-up. My tumour load had shrunk by so much by the time I began the venetoclax ramp-up, I didn't need any additional observation beyond when I was first given 20mg of venetoclax during my fifth obinutuzumab infusion.

Neil

[Phil4-13]

Thank you, SeymourB, for a precise and easy to understand explanation on TLS. 🙂Sandra

[SofiaDeo]

It's not so much "common", it's something to be prevented. There is no way to know ahead of time, how sensitive ones' CLL variant will be to any medicine. Some people start killing CLL rapidly, others take longer. The idea is to be aware, monitor, and prevent/mitigate.

[elm1]

thanks

[gardengirl80]

I had a slight case of TLS during the first infusion of Gazyva at the infusion center (not hospital). The nurses were right on it as soon as it started and they had the necessary meds handy to give to me. They are properly trained and know what to give to counteract it as soon as it starts. They paused the infusion, gave the meds and continued to observe me. After approx. 1/2 hour they continued the infusion and I had no further problems except for extreme tiredness the following few days. I had no reactions to Venetoclax which I am still taking.

[SofiaDeo in reply to gardengirl80]

Tumor Lysis Syndrome is not an Infusion Related Reaction. What you are describing is a common IRR with obinituzumab.

TLS doesn't occur within minutes. It's defined as a series of changes in bloodwork, and a few other parameters. It's most commonly seen in solid tumors, or fast growing leukemias, which is probably why the original venetoclax researchers weren't monitoring for it.

ncbi.nlm.nih.gov/books/NBK5...

"Laboratory Diagnosis of Tumor Lysis Syndrome

Requires 2 or more of the following criteria achieved in the same 24-hour period from 3 days before to 7 days after chemotherapy initiation:

Uric acid 25% increase from baseline or greater than or equal to 8.0 mg/dL

Potassium 25% increase from baseline or greater than or equal to 6.0 mEq/L

Phosphorus 25% increase from baseline or greater than or equal to 4.5 mg/dL (greater than or equal to 6.5 mg/dL in children)

Calcium 25% decrease from baseline or less than or equal to 7.0 mg/dL

Clinical Diagnosis of Tumor Lysis Syndrome

Laboratory tumor lysis syndrome plus 1 or more of the following:

Creatinine greater than 1.5 times the upper limit of normal of an age-adjusted reference range

Seizure

Cardiac arrhythmia or sudden death

Other origins of AKI should be excluded.

In the evaluation of tumor lysis syndrome, the following studies are necessary:

Imaging

X-Ray and CT scan of the chest to evaluate the presence of mediastinal mass and the presence of a concomitant pleural effusion

CT scan and an ultrasound of the abdomen and retroperitoneal structure if the mass lesion is located in the abdomen or retroperitoneum. Care must be taken with intravenous (IV) contrast because of the presence of AKI in tumor lysis syndrome.

Electrocardiography (ECG)

ECG is part of the workup for patients with tumor lysis syndrome to check for findings associated with hyperkalemia and hypocalcemia. Hyperkalemia is a potential cause of fatal arrhythmia in tumor lysis syndrome.

Complete Blood Count (CBC)

CBC helps in the diagnosis of malignancy associated with tumor lysis syndrome. The hallmark of most malignancy is leukocytosis with anemia and thrombocytopenia.

Comprehensive Metabolic Panel (CMP)

The metabolic derangements associated with tumor lysis syndrome are hyperkalemia, hypocalcemia, hyperphosphatemia, and hyperuricemia. Blood urea nitrogen (BUN), creatinine, and lactate dehydrogenase are also elevated in tumor lysis syndrome. CMP must be monitored between two to three times daily before and after initiation of therapy. Elevated laboratory value might be indicative of the beginning of tumor lysis syndrome.

Urine Analysis

Precipitation of uric acid salt can cause obstructive uropathy. In the treatment of tumor lysis syndrome, alkalinization of urine with sodium bicarbonate is the standard of care. Frequent urine analysis with an assessment of urine pH, specific gravity, and output is mandatory."

[bayside64]

I had TLS in 2021. Clinical. Occurred while in the hospital. A year and half later, I completed 12 months of Venetoclax and achieved MRD.

[elm1 in reply to bayside64]

That’s encouraging.