I have SLL and will be starting V&O treatment next week. Apparently I will have two months of obinutuzumab (typical cycle 1 ramp up and a second cycle) before starting venetoclax. After that, it will be 6 months obinutuzumab and 12 months venetoclax.
Seems this is due to potential TLS issues.
Anyone have treatment similar to this opposed to starting venetoclax on cycle 2 of obinutuzumab?
I had a similar approach to reducing the risk of TLS. Cycle 1 of my V+O treatment + acalabrutinib, consisted of the first cycle with acalabrutinib, introduction of obinutuzumab in cycle 2; (split first 1,000mg 100/900mg, followed later by 3 full 1,00mg infusions), with the venetoclax ramp-up starting in cycle 3. I had a very enlarged spleen and didn't need admission for hospital observation for signs of TLS during the venetoclax ramp-up.
Neil
Good to know.
Was expecting venetoclax 12 cycle regimen per the prescribing info, but it seems to makes sense from TLS perspective to shrink nodes before starting venetoclax. I am in high risk cagatory given the node size and lymph count.
Debulking nodes with either a BTKi or O seems to be a fairly standard approach from the webinars I've listened to. I'm sure O works, but leading with a BTKi appears preferable and I think faster.
Bigfoot
The BTKi 'brutinib' + BCL-2 'toclax' synergy works well, with a BTKi drug pushing CLL cells from the nodes and spleen into the blood for a BCL-2 drug to destroy. Of note, for those in my clinical trial on the A+V arm, were given two acalabrutinib cycles before the introduction of venetoclax. In some people, CLL cells can hand around in the blood stream for quite a few weeks (see image), before the lymphocyte count (ALC) drops below the starting baseline count, so they could still be at risk of TLS when a BCL-2 drug is introduced.
Neil
Neil,
thank you for the explanation of how the two types of targeted therapies work together.
I am wondering if that process continues after the initial pushing out?
I started Zanabrutinib around April 19, 2024 and then Venetoclax on July 3, 2024 with IV fluids, outpatient, for the first two days of the first two weeks of the "ramp up" period and had a Neupogen shot either July 10 or July 11 ( in the "day hospital" where I got the IV fluids after labs came back showing zero ? (blanking on the word.)
GOOD LUCK to roninwarior007 !
BTKi drugs work in part by reducing adhesion signalling, so they will keep doing that as long as there are CLL cells not in the blood.
Thanks. I will have to read more to try to understand your answer about adhesion.
If you know, are cells inside the bone considered in the blood or not in the blood?
My brain and orbit MRI's show something going on in the skull itself (calvarium and base) as well as in vertebrae.
CLL cells can either be carried within the blood, where they are in their dormant phase, or surrounded with a supportive microenviroment in the nodes, spleen), a specialised node, or the spongy bone marrow, where they are in their active phase. It's the CLL signalling that keeps the CLL cells adhering in these latter locations, where they are protected and sustained. They can also accumulate in other organs, or less often in the CNS. To eliminate them in the CNS, you need fairly small molecules. BTKi drugs do well getting through the CNS and venetoclax can also penetrate it, though it's a larger molecule than the BTKi drugs.
I expect you'll see an improvement in your CNS involvement from your treatment.
Neil
I am currently on this treatment. It saved my life. Side effects have been minimal. First few months are tough due to blood tests and infusions. Before you know it, it infusions will be over, your numbers will be great, and your anxiety will be much less. I promise.
Thanks as I start V&O treatment today that is good to hear
Exactly how my treatment began and proceeded til the end. The only hiccup was covid, which caused a 5 day stop of the Ventoclax while I took Paxlovid.
I only had day one and two of Obinutuzumab. The effect of those two days was amazing. Lymph nodes vanished and blood numbers returned to normal. I was put on Venetoclax within a few days and had no adverse response during the ramp up.
I imagine that TLS concern is the reason for your additional month if you have high blood numbers and larger lymph nodes.
Europe has approved Ibrutinib + Venetoclax. There is a 3 cycle lead in of the BTKi Ibrutinib before the Venetoclax ramp-up.
V+O there is normally a 3 week lead in of O with 1000mg IV each week before Ven ramp-up.
About 20% are "high risk" TLS at start. Restaging before Ven ramp-up finds about 2% are still high risk. Additionally due to creatine clearance there are still some that need to be in hospital for the 20mg and 50mg doses of Ven. Seems to be a higher proportion of I+V. V+O has a greater proportion of patients move to low risk TLS.
Is one extra dose of Obinutuzumab in outpatients lower cost than two 3 day / 2 nights stays in hospital?
I was one of the 2% that failed to convert from high to medium/low risk on V+O. This took my doctors by surprise, the CT scan wasn't ready the day before 20mg start of ramp-up and the doctor offered me the choice to wing it with blood tests in outpatients or wait for the scan results. I elected to wait, 6 hours later I was told I would be admitted the next day, CT scan showed nodes were still large. I felt such a fraud being on the ward when I was fit and well. NHS hospital beds are a finite and limited resource. TLS blood tests show my WBC jumped from low single digit 3 days before into teens during the 50mg dose and 4th Obin IV, 13 days after previous Obin IV and remained in the teens for all 3 days I was in hospital. Dropped back to low single digit before the 100mg dose. I don't know if this was because I had used all the Obin between dose 3 and 4 or if the Venetoclax was evicting the remaining lymphs from the nodes faster than it could be found by the fresh dose of Obin.
as part of the celestial trail by beigene I just finished the second cycle of rampup with venetoclax.
Due to large lymphnodes and enlarged spleen I am in the riskzone.
During the first month of Obi Infusions , prior to the Iv, they gave me an Iv of Rasburicase, sold under the brand name Elitek in the US and Fasturtec in the EU. On a daily base I am on Allopurionol. Both preventing TLS.
I guess that will be a standard procedure for V&O.
I have had no side effects at all. Only the good ones! My energy levels are increasing. The bad days are there still, but I’m hopefull for the better time will come.
I wish you all the best!
roninwario007,
I understand that you are asking for opinions from others who have been treated with the O+V combination, yet, in my view, the data from clinical trials would be your highest measure.
JM
My question was more about the extra cycle of obinutuzumab prior to starting venetoclax.
Lot of good/interesting information shared above.
There likely is something in your personal and/or medical history, or some other reason, that has your doctor wanting to modify the standard protocol. Ask them why.
👍
Working while on treatment O&V
Swollen legs on O&V
Cll treatment 
News about V+O and Acalabrutinib from EHA
