venetoclax and obinutuzumab treatment for cll

[dellkota]

Hi, I have finished the above 12 months treatment for cll tp53 mutated, I now have 2 monthly checks and my lymphocytes are low, is this a cause for concern?

[AussieNeil Administrator]

This is actually what you want to see, because it means that your CLL treatment has done very well in reducing your blood tumour level. I started acalabrutinib plus venetoclax and obinutuzumab treatment 4 years ago this month and my lymphocyte count is still low - towards the lower end of the normal range. That's mostly because I have more CD8 cytotoxic T cells than is usual for healthy folk, but is not unusual with CLL. My B cell count remains very low. I only know that because of clinical trial related blood test monitoring.

Enjoy your remission and may it be a very long one.

Neil

[dellkota in reply to AussieNeil]

Thanks very much for your reply my friend, that certainly eases my mind, you have done well to be in remission for so long and may it continue

[RSilver in reply to AussieNeil]

Just to clarify your statement that you started "acalabrutinib plus venetoclax and obinutuzumab treatment 4 years ago", Are you still taking any of those? Specifically the Acal?

I started Obin and Ven this November with the expectation that I will finish Obin after 7 months and finish Venetoclax after 12 months when I expect to be in remission. Do I have an incorrect expectation with this time limited therapy?

[AussieNeil Administrator in reply to RSilver]

Combination therapies with Venetoclax are fixed term, with some including an extension to improve the percentage of participants achieving uMRD. My trial was modified to closely match a similar Dana Farber AVO clinical trial. I took my last A+V dose almost 3 years ago, after 14 cycles (about 13 months) on acalabrutinib.

Neil

[RSilver in reply to AussieNeil]

Thanks for clarifying Neil

[fraxus1 in reply to RSilver]

The Euro CLL center studies, particularly CLL13, show that a large percentage (no 17p deletion) pts remain well 3yrs after. And the survival curves flatten - suggesting a longer remission. See this paper esp fig3.

nejm.org/doi/full/10.1056/N...

[AussieNeil Administrator in reply to fraxus1]

Thank you. This is the Kaplan - Meier plot I was unable to find. AVO Progression-Free Survival results are similar to those of IVO, with acalabrutinib having a lower side effect profile to ibrutinib's.

Neil

IVO and IV PFS plots are similar, with IVO eventually showing a slight advantage.

[dellkota in reply to AussieNeil]

Hi again Neil, I just wanted to add is that my lymphocyte count is below the nomal range and the hematologist says it's a bit of a concern because of suppressed immunity and fighting of the cancer, kind regards Dell

[AussieNeil Administrator in reply to dellkota]

You need to know the mix of lymphocytes to determine how immunity may be suppressed, but even with good lymphocytes, T cell exhaustion can be an issue. Certainly, the risk of opportunitistic infections (e. g. shingles for me) can be an issue, so you should probably be on valaciclovir or aciclovir. Secondary primary cancers are something of which we all need to be wary - having regular skin check-ups and recommended screening for bowel, breast, prostate and other cancers as appropriate.

For me, I'm still doing better than before treatment, when I was averaging a week in hospital roughly every year for IV antibiotics. It's now nearly 4 years since my last hospital admission for an infection. A chronically low neutrophil count puts you at more of an infection (but not cancer) risk, than a low lymphocyte count.

Neil

[dellkota in reply to AussieNeil]

Thanks again Neil, I appreciate all of the information I've received from you. It's early days for me and probably I will be given medication at some point. Cheers my friend!

[skipro in reply to AussieNeil]

Neil

How often are you having colonoscopy?

[AussieNeil Administrator in reply to skipro]

My GI surgeon recommends every 5 years. Australia also runs a free Faecal Blood Occult Test screening program, which is voluntary. I tested negative this year and in previous tests.

[mdsp7 in reply to AussieNeil]

I was on acyclovir for a chronic herpes infection. Every time I went off the acyclovir, the infection came back. I read about it online and learned that ration of amino acids arginine and lysine play a role in the reproduction rate of the virus.

I read that a high arginine/lysine ration gives the herpes virus many of the materials that it needs to replicate. Alternatively, a high lysine/arginine ration prevents the virus from replicating as well. So I looked up foods that contained each amino acid and saw that peanuts would contribute to herpes reproducing while hard cheeses and yogurt would do the opposite.

I tried altering my diet to include more yogurt and none of the high arginine foods when I started having outbreaks. It worked very well and I have not needed acyclovir for years now. During times of stress or high exposure to the sun, I eat a lot of yogurt and stay away from nuts. Try it. I hope some of you will find that it actually helps you feel better.

I was very glad this worked for me because I didn't tolerate the acyclovir very well, it made my spleen area feel swollen.

[skipro in reply to AussieNeil]

Neil,

Question about CD 4 and CD8

In the HIV lit. a CD4/CD8 ratio of less than 1 and particularly 0.5, the person is considered high risk for infection particularly Pneumocystis

I bring this up because when I started V + O

my CLL specialist repeatedly told me that getting FCR was like giving me HIV and that and that V + O was nothing like that

Interestingly, 8 months into V + O, my CD4/CD8 ratio is 0.5 snd identical to what it was during FCR.

The only difference is that both CD8 snd CD4 during FCR were normal whereas now CD4 is low end of normal and CD8 at high end of normal

So just curious if you have thoughts on the T cell aspect of my current immunity on V+O compared to 2018 on FCR?

[skipro in reply to skipro]

Correction

During FCR CD4 was very low, CD 8 was slightly low

[AussieNeil Administrator in reply to skipro]

There's certainly some insights from HIV research applicable to the impact of CLL and CLL treatments our cellular (T cell immunity). That's because both FCR and venetoclax knock out some T cells in addition to the much better targeted B cells. The difference is that venetoclax more selectively targets BCL-2, though with FCR , in addition to the general targeting of lymphocyte cells by the FC, you have some selective targeting of a subset of T cells expressing CD20 from the rituximab. However, per pubmed.ncbi.nlm.nih.gov/359... "Unfortunately, our understanding of these cells is still at its infancy and ongoing study in a wider range of pathologies is required."

As has become apparent from the research on the impact of SARS-CoV2 and vaccines on our adaptive, specifically our cellular (T cell) immunity, it's much harder to unravel how the different T cell subsets affect our immunity, even more so when CLL related T cell exhaustion is taken into account, than investigating the effect of CLL and CLL treatments on our humoral (B cell) immunity.

Neil

[Pacificview]

I am on cycle 9 of Obin/Ven. As a comparison, my ALC is .8 which is also low normal. Its been as low as .6 end of May up to 1.2 and now having trended down to .8ANC holding steady now at 2.5 for months. My ANC low was 1.0 in June. So ANC slow trend up since then.

HGB..13.4

Plts 153

Percentage Lymphocytes since you might also want to compare...23

Percentage Neutrophils....68.4

My Doc says I have been in remission for months. Loves my numbers. So that gives you someone to compare to.

I end treatment in April.

All the best and Merry Christmas!

[dellkota in reply to Pacificview]

Hi, thanks for the information, certainly does give me something to compare to, my only concern as mentioned is the low lymphocyte count after finishing my 12 month treatment but very similar to yours, I'm glad you are doing so well my friend and a very Merry Cristmas to you also!