What do you do when you are MRD Negat... - CLL Support Assoc...

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What do you do when you are MRD Negative?

profrich
profrich
32 Replies

I just learned I am MRD negative on Venetoclax and Rituximab. We had been planning on adding calquence. My doctor still wants to do that. It seems he wants to hit it hard while it is down. On the other hand, I'd like to relax and save the meds for later. So, perhaps just stay on a reduced dosage of venetoclax.

I would guess different doctors have different views on how to handle this. I am curious as to what others have done.

32 Replies
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PlanetaryKim

Congratulations on MRD-negative, profrich! I don't know the answer to your question about how different doctors proceed at this point. But well done!

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Mldeterm

You celebrate first of all! I've not heard of others adding a lighter hitter like acalabrutinib after hitting MRD- on Venetoclax but I don't think anyone has any answers on best path yet. My husband started with ibrutinib/gazyva to debulk ahead of adding venetoclax. He's on a trial which stops all meds after 19 cycles (months) whether MRD- or not to see how long the remission lasts. Best of luck with whatever you choose! Mindy

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Ivotedfornixon

one of your posts 2 months ago said you were already taking acalabrutinib then went to venclexta. I am not a physician-i would do what your doctor recommends

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Mcpill

Yesterday Len (lankisterguy) posted 2 wonderful patient power videos: "Patient Power Video updates on Blood Testing and New Treatment updates". I have not finished them yet, but was so happy to see a discussion on when/if to stop treatment on Venclexta for those who are 17p del. I do not know your markers. I am 17p del and have been on Venclexta since Sept 2017. I have been MRD neg (blood- no bmb thankfully) since October 2018. I was on Imbruvica from March 2015 til Sept 2017. W and W for one year prior. As noted in the video Len posted, it is difficult to know what to do. Venclexta is such a new drug and there is not a lot of data available. Not everyone who takes it reaches MRD neg, and some of those who do and stop taking it, are back on again within a year. The patient power presentation indicated that there is a trial at Memorial Sloan Kettering on this subject, and I will be searching for it. I believe the trial keeps patients on Venclexta for two years and then gives them the choice to continue or not. They will monitor the results. I am hoping more data will be available in a year or two. I have been fortunate on both drugs- no neutropenia etc. I have another appointment in September, and will see what the tests show. For now I plan to continue on Venclexta until more data is available.

Wishing you all the best with your decision,

Susan

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profrich

Thanks for the info. I do not plan to stop V. My predicament is whether to add calquence. Have you reduced your dosage of venclexta?

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Mcpill
Mcpill
in reply to profrich

I have not. Hoping to stay on until results of trials and other data show it is safe. Sorry, thought you were considering reduced dosage on Venclexta as well. All the best.

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profrich
profrich
in reply to Mcpill

I was/am considering reducing dosage. It depends on my neutrophils.

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LovecuresCLL

Why do you want to reduce your dosage of V? Just curious as I am on it as well.

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profrich

Side effects, mainly neutropenia. Venetoclax is very strong (I think 10 times as strong as impruvica). Some think you don't need that much anyway.

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Hoffy

Dr. Kipps of UCSD generally feels not to treat once you get to MRD- Undetectable.

I am in that situation,

I was on I plus V for 15 months.

You could maybe do a little more then stop ( 3- 6 months? ..) ,

Hoffy

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profrich
profrich
in reply to Hoffy

My good friend Melioria is seeing Dr. Kipps also. She told me he does not over treat, but I did not realize what you said. So, you are doing nothing now?

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Hoffy

I am on the Captivate Clinical trial. I got to MRD-U so now I am on either Imbrvica or a placebo. Since the side effects went away I am very likely on a placebo.

Other people I know with Kipps go off treatment after MRD-U. He feels you should not treat if you do not see CLL,

Be well,

Hoffy

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profrich
profrich
in reply to Hoffy

You be well, also,

Thanks,

Rich

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LovecuresCLL
LovecuresCLL
in reply to Hoffy

Did he use a flow cytometry to look for the tumor lymphocytes or did he do sequencing? Sequencing is a lot more sensitive than flow cytometry. I was just curious.

Congrats on being MRD-U. That’s great news.

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Hoffy
Hoffy
in reply to LovecuresCLL

I think they used flow cytometry. It goes down to 1 in 10,000 cells. Sequencing goes lower I am told,

Thanks,

Hoffy

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HopeME

What would I do if I was MRD negative? It is simple. I’d celebrate.

Good luck,

Mark

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LovecuresCLL

Congratulations on MRD negative. That’s great!

I like your doctor’s idea. That is a winning triple combination. You don’t want it to relapse ever. He may “cure” you. May be you should let her/him try Calquence as he is attacking the clones from every angle. Three drugs going after multiple different receptors (BTK, CD20 and bcl-2.)

They think that triple combination can put you into a remission for as long as they have data.

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profrich

What do you mean by "for as long as they have data?"

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AussieNeil
AussieNeilAdministrator
in reply to profrich

We only have limited data on muticombination non-chemo treatments, because they are so new. We won't know how long such combinations can induce remissions until trial participants have lived long enough in remission to provide that data.

Neil

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mnmnewtons

The question you are asking cannot be answered without knowing your cytogenetics, like tp53 deletion, type and number of clones and IGHV status. Also there are a few different levels of undetectable (or negative) MRD. uMRD does not mean you are totally free of all cancerous B cells. That being said, there are clinical trials to test outcomes of lower monotherapy doses as a way to limit drug resistance and multi-drug combinations (like Venetoclax, Calquence and Rituximab) to knock the cancer down, leading to treatment "vacations". The effective long term results are not in yet.

I became uMRD <1 in 40,000 on Venetoclax and Rituxan then stopped and switched to Calquence. After a month of Calquence my lymph nodes and spleen returned to normal size. Guess the bad B cells were hiding in there. After about a year of Calquence monotherapy I am still uMRD at <1 in 10,000 in the blood. I have complex karyotype, TP53 deleted, IGHV unmutated. Let us know what you decide and how it goes.

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profrich
profrich
in reply to mnmnewtons

Turns out I am in the same boat as you. Even though I am uMRD, I have enlarged lymph nodes (from a cat scan). So, I am going to take Calquence also. I have a few questions for you:

1. When you switched to calquence did you stop veneotoclax immediately or take both until your lymph nodes shrunk?

2. Did your lymphocyte count jump a lot when you went on calquence? It seems it would. How high did it go?

3. Did the lymphocyte count go back to normal in a month?

I want to know what to expect.

Thanks,

Rich

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mnmnewtons
mnmnewtons
in reply to profrich

I cannot tell you what to expect only what happened to me. After 7 months of uMRD, on Venetoclax including the last 6 months also getting Rituxan once a month, we decided to stop Venetoclax (and Rituxan) and start Acalabrutinib, 100mg every 12 hours. Two reasons: with my cytogenetics we thought it advisable to save the Venetoclax for later before developing resistant clones; also it was apparent that my lymph nodes still harbored "rogue" B cells.

The transition was seamless except for diarrhea, now mostly controlled. In 2 months, verified by CT scan, my lymph nodes shrank to normal levels, as well as my spleen. My white cells have never gotten above 4.0 and other blood measures were never the worse for it and now approach the bottom of normal. Absolute neutrophil count has been around 2.0 and platelets have hovered around 100.

We never know what to expect, or what might be around the corner. Be self aware and vigilant. Let me know how thing are working out.

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profrich
profrich
in reply to mnmnewtons

You lymphocyte count did not shoot up soon after you started calquence? My ALC went way up when I started Ibrutinib (which I had to quit) because of the lymphocytes being purged from the lymph nodes and spleen.

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AussieNeil
AussieNeilAdministrator
in reply to profrich

The temporary jump in lymphocytes when starting Ibrutinib/Imbruvica, only happens in about two thirds of those taking it. Some patients experience long term raised lymphocyte counts on Ibrutib, but still experience a good outcome. I presume similar patterns occur with acalabrutinib/calquence, but have yet to see reports about this.

Neil

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profrich
profrich
in reply to AussieNeil

However, the increased count is due to lymphocytes being purged from the lymph nodes and spleen, which happened with mnmnnewton. So, I don't see how he/she avoided it.

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AussieNeil
AussieNeilAdministrator
in reply to profrich

From the Imbruvica website:

"Lymphocytosis is an increase in the number of lymphocytes in the blood. Therapies that interfere with trafficking and adhesion of malignant lymphocytes by disrupting B-cell signaling can result in treatment-related lymphocytosis"

It's not a given that it will happen per - "Treatment-related lymphocytosis occurred in 66% of patients treated with single-agent IMBRUVICA® across the CLL/SLL registration studies", so around a third of patients do not see their lymphocyte count climb while on Imbruvica/Ibrutinib:

imbruvicahcp.com/cll/safety...

Note also the wide range in how long it lasts - "In the CLL/SLL registration studies, the onset of isolated lymphocytosis occurred during the first month of IMBRUVICA® therapy and resolved by a median of 14 weeks (range, 0.1 to 104 weeks)" . If it resolved quickly, (0.1 weeks is less than a day!) depending on the timing of your blood tests, you may not be aware that it had even happened.

Here's the editorial in Blood discussing a paper in the same issue, which proposes a reason for the prolonged lymphocytosis in Ibrutinib observed in some:

bloodjournal.org/content/12...

Woyach et al identify 20% of CLL cases that responded to ibrutinib but showed a prolonged lymphocytosis, defined as an elevation of the tumor lymphocyte count that had not resolved to normal or <50% of baseline within 12 months.

Neil

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mnmnewtons
mnmnewtons
in reply to profrich

History: I started my journey of treatment with one treatment of Treanda and Rituxan. My chromosome 17 deletion and TP 53 deletion called for the newly approved targeted treatment, Ibrutinib. I lasted a couple of months on that and had to stop because of a serious rash which was not controlled. After 15 successful months on Idelalisib, I transitioned to Venetoclax. After several months on Venetoclax we added 4 months of Rituxan. I was uMRD for several months when we decided to QUIT Venetoclax and start Acalabrutinib. After 4 months on Acalabrutinib alone, my lymph nodes had returned to normal.

I have no answer for your dilemma regarding lymphocyte count. In my case, the more usual treatment sequence could not be followed. Acalabrutinib followed the Venetoclax plus Rituxan. Maybe there is something to that. Maybe not. If you are looking for certainty you certainly will not find it.

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profrich
profrich
in reply to mnmnewtons

Thanks. The lymphocyte count thing is not really a dilemma. I am just wondering if yours went up (like I thought it would) when you switched to Acalabrutinib. I guess you are saying it did not.

I have had a hard journey involving many med like you.

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profrich
profrich
in reply to mnmnewtons

I am not looking for certainty, but you are the only data point I know similar to my situation. Can you clarify? Was it 1, 2, or 4 months after starting Acalabrutinib that you nodes went back to normal?

Thanks,

Rich

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mnmnewtons
mnmnewtons
in reply to profrich

Please excuse my imprecision. 10/18/18 I stared Acalabrutinib. By the second month some friends noticed the lymph nodes in my neck were not visible any more. After 6 months, a CT scan confirmed that all lymph nodes viewed and my spleen were within normal limits. My guess is that that had happened much sooner than the scan.

My conclusion was that Acalabrutinib had done what Venetoclax had maybe not done. That is, push the cancerous B cells out into my blood. Then what was left of the Venetoclax and the new Acalabrutinib could get them. I believe I did not have lymphocytosis because the Venetoclax (and to some extent the 4 infusions of Rituxan) had severely depleted them and I guess Acalabrutinib just finished them off.

That is my impression of how it happened but that is not scientific evidence.

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Motoli

As pointed out by others there is no clear path to follow after having reached UMRD status, it seems. Hence, answers to the question of whether adding acalbrutinib posterior to your treatment helps or not are conjectures at this point.

However, there is something that we DO KNOW (sounds like Bernie Sanders): Calquence will add to your adverse effects, thus taking quality of life time away from you. It may or may not help, but it is for sure that adding it to the cocktail must have a cost. My decision would be to stay put with your UMRD stats and wait until there is a relapse; hopefully, this will not happen.

Important: most of these new agents have been evaluated in terms of progression free-survival, with small or unknown differences in overall survival, as the agents are so novel and there is so little data. Hence, an important part of the strategy should be to increase the quality of life post-treatment. Given that we do not know that acalabrutinib will kill the beast (may be your CLL is already gone), I would save if for another battle, should there be one.

This is a truly gray area, and sometimes one needs to temper the agressiveness of some doctors. There are horror stories of overkill in medicine, like the times of radical surgery in breast cancer under the reasoning that the "more you remove, the better you chances will be".

Good luck and congrats on your UMRD status.

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profrich
profrich
in reply to Motoli

You make excellent points. Thanks, Rich

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