Move over MRD Negative and make way f... - CLL Support Assoc...

CLL Support Association
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Move over MRD Negative and make way for MRD Undetectable

As Dr Brian Koffman mentioned here: healthunlocked.com/cllsuppo... part of his contribution to the European Hematology Association (EHA) 2019 Amsterdam congress ehaweb.org was as a panel member on a satellite event sponsored by the MRD Testing Collaborative, namely the Impact and Barriers to MRD (Minimal Residual Disease) testing. My wife and I were thrilled to be invited to this session by Dr Koffman and his wife Patty and to be able to spend some time with them.

The MRD Testing Collaborative initiative began 18 months ago, with the aim of improving the knowledge of the relevance of MRD testing among specialists and patients, encouraging its use (it's very low), by educating patients about how MRD testing can influence their treatment and prognosis post treatment, so that they will ask their doctors about it. In parallel, the collaborative is establishing a process to put patients in touch with resources familiar with the use of MRD testing for their particular blood cancer, e.g. from the Leukemia and Lymphoma Society: lls.org/sites/default/files...

MRD Undetectable (MRD-U) rather than MRD Negative is the new jargon, which Dr Koffman supports. There was a consensus that that's what patients want to hear - "We can't find any evidence of your cancer remaining, it's undetectable". MRD Negative is confusing - does it mean you didn't reach MRD?

Liz Wolfe, interim CEO of Stupid Cancer was the organiser. Panel members were Lizette Figueroa, Director, Education and Support, Leukemia and Lymphoma Society, Dr Koffman, Zack Pemberton-Whiteley, Patient Advocacy Director, Leukaemia Care, Dave Fuehrer, CEO of GRYT Health - grythealth.com/about which is similar to HealthUnlocked but for a younger demographic.

Dr Koffman covered in his panel address how MRD-U in the CLL world has gone from being valuable with FCR to being immaterial with Ibrutinib, where MRD-U was rarely reached, to being important again with the short term, non-chemo treatments currently being trialled. He noted that it's a surrogate for assessing the performance of treatments, particularly in trials, but we need the data to validate that reaching MRD-U with newer treatments does indeed translate to long remission times.

After the panel session, it was great to learn of the success of the CLL Society cllsociety.org and the future plans for the society - but given the dedication of the Koffmans to their cause, that success is not surprising. As Brian says, "We are all in this together", ensuring we know enough about our disease to find specialists that are keeping up to date with the fast changing CLL monitoring and treatment landscape i.e. "Smart Patients Get Smart Care". Hence the CLL Society's focus on establishing support groups "30 established and a further 15 in the pipeline" according to Patty and on educating doctors and providing video access to recognised specialists for those unable to find a CLL specialist through the CLL Society Expert Access program: cllsociety.org/cll-society-... . Brian mentioned the challenge of specialists in just CLL staying abreast of changes in his address from the panel and has separately shared about his new focus on bringing in "new blood" research specialists through CLL Society support.

In closing, given Dr Koffman's CAR-T therapy just over a year ago, I was interested to note that the incoming president of the EHA is Prof John Gribben of Barts Cancer Institute, London, United Kingdom, here speaking with ecancer at EHA 23 about the development of EHA Topics in Focus, and the educational emphasis being placed on CAR-T cell immunotherapy: ecancer.org/video/7012/educ...

Neil

PS Brian and Patty, congratulations on your 43rd wedding anniversary celebrated in Amsterdam!

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Neil

So nice to meet you and your wife in Amsterdam . Thanks for all that you are doing for the CLL community

Brian

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It was great to hear personally from you and Patty of your plans for the CLL Society that, funding permitting, will do much to continue the momentum lately achieved in CLL treatment developments and translate those gains into a significant personal health improvements for all of us living with CLL world wide. Attending events like EHA and ASH brings home how interconnected haematological research is and how leukaemias present a powerful avenue for exploring cancer not easily achieved with solid tumours. I hope the CLL Society is able to realise your vision of encouraging new researchers into a very exciting field.

Neil

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We need to be sure all have access to their best possible care. And that's starts with knowledge.

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Happy 43rd wedding anniversary Brain and Patty!

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Well heck, I just got back from Amsterdam Sunday. I would have bought you guys a beer. Or met at a coffeehouse. 😎

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Thank you very much Neil and Brian!😍

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I appreciate another great article from AussieNeil. Nice photo.

So FISH is used for undetectable and flow for MRD?

So how do we get our specialist to use the former technique if that’s not their protocol. And if one technique is negative and the other is positive. Do we say “Hey Doctor is there still a little left here?”.......”Did you use the more sensitive lab technique for MRD?” In the real world when you are trying to get the doctor to even listen in the first place and spend more than ten minutes with you.....not sure how we can question them on how they are doing their labwork.” I for one cannot ....I am already asking too many questions with my huge notepad and all this information now in my head. I can barely get them to give me more than one treatment choice. Or notice how sick I am. Everyone keeps saying get another doctor, but you have to be patient and kind with these doctors. Doctors are human too and they have to get home to dinner too and feed their dog. They don’t sit reading every night. They need a life too. This pace is so fast. New drugs and combinations are starting every month practically. It is great news but I am finding the situation to be a bit chaotic. Is anybody with me on this?

I not trying to challenge anybody I am just trying to practically apply this to my current situation. I can tell you right now my current doctor is doing flow to detect which is 1/10,000 cells right? which is not as sensitive as the MSD-U. So even if he treats me soon and finds cells with the more sensitive technique....what does he do with the information? Treat me again?

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Flow Cytometry is used to (reasonably) uniquely identify CLL as opposed to other blood cancers and FISH testing looks for common DNA errors within the CLL diagnosis. It uses a panel of probes that look for specific errors, like 11q, 13q and 17p deletions. There are a number of different techniques used to search through a sample of cells and look for cancer cells, namely Flow cytometry and PCR for CLL according to the Leukemia and Lymphoma Society MRD fact sheet, updated this year, with Next Generation Sequencing likely in time I expect: lls.org/sites/default/files... I expect (hope!) that this initiative will result in pressure to standardise on the best testing technique, similar to what's happening for IgHV testing in CLL, but for all blood cancers. As part of that, hopefully we will move to a standard naming convention that tells us how many cells have been checked, such as UMRD-6 and perhaps UMRD-7, 8... as mentioned by avzuclav.

Neil

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I meant to also say that hopefully the personal benefit of MRD-U testing will be being able to finish a treatment course earlier. With FCR and BR chemotherapy treatments, if you can't find any CLL cells after say 4 courses, why risk further bone marrow damage, neutropenia, etc ? Also finishing earlier saves on medical costs and frees up hospital beds for the next

patients awaiting treatment. With the newer non-chemo treatments, the much greater cost of taking targeted therapies for additional months that are not needed can be saved. That is particularly attractive to universal health care countries and could swing the decision to replace chemotherapy treatments with newer, targeted therapies. All this of course is reliant on evidence that shorter treatment cycles when MRD-U has been achieved, still results in an equally long remission to that achieved from a longer treatment cycle.

Oh, and the 'photo' is from the EHA website - sadly not my work :(

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Well it’s a brilliant to do that. But things in medicine are slow to change. I cannot make these kind of demands to the specialist . It is up the the society of oncology to pressure them. It’s due to cost too. The cost is higher too. It’s your life and one disease and there may be other priorities . That’s why socialized medicine is bad. We need capitalism to drive down the cost.

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Honestly, I think we need a mix of approaches. We wouldn't have the new drugs for CLL without the incentive of capitalism WITH effectively guaranteed profits for successful drugs by government encouragement of orphan drug development. Then there's the issue of drug costs not going down, but going up, when the development costs have been well and truly recouped.

I personally find it very sad that so many families in the USA go bankrupt because of unexpected medical costs or that the largest purchaser of drugs in the USA - the US government, is legally prevented from negotiating for better prices as other countries are able to do.

I think there's a good argument for a mix of private and public health funding.

Neil

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Good points, more information is almost always better than less.

I was originally being treated by a bright young oncologist who came highly recommended. After reading how important IGHV testing can be for prognostic purposes and to inform treatment choices, I asked him if such tests were run on me. He acted like I did not know what I was talking about and said such testing was unnecessary.

Three weeks later I posed the same question to my doctor at MD Anderson who I had gone to for a second opinion. He told me he thought IGHV testing was critical for me to inform treatment choices. I never returned to the general oncologist after that day. He was a nice guy, very bright and I think motivated to do his best for me. I just think with all the advances in so many cancers, no one oncologist can keep up with all the literature on dozens of cancers.

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That's why we go to specialists because they do keep up with all that's new. I have two doctors, an oncologist and a CLL specialist.

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Exactly. "Smart Patients Get Smart Care", so I would expect that our community members will add years onto their survival time from what they learn here, including finding a specialist who DOES keep up with the latest developments and implementing the best community tips on how to live well with CLL summarised here: healthunlocked.com/cllsuppo...

Neil

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This is great to see! Instead of MRD Undetectable, can we all agree to use the more elegant nomenclature put forward in the MD Anderson paper?

UMRD-6 and UMRD-4, which give us the specificity of the tests.

source:

bloodjournal.org/content/13...

Any idea if the clonoSeq testing will get approval for CLL? They used to promote CLL more on their site. Check out the MRD tracking report section of this PDF:

clonoseq.com/sites/default/...

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Is anyone thinking about cost here. Who is going to pay for all this? I pay $2000 per month in insurance for me and my wife now. Do you buy whatever you want in the grocery store and expect somebody else to pay for it? When you start putting cost on this website we can discuss further. I cannot even say “I will pay for the testing MRD U to these doctors” . That doesn’t work in the States. We are quasi socialized too. Everybody gets hamburgers fries and a coke.

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I would expect that the cost of MRD-U testing would be dwarfed by the savings in unnecessary additional treatment with the associated related costs of increased hospital admissions for infections. :) On that basis, I would expect that insurance companies would be thrilled to fork out a few thousand dollars, given that they have the chance of saving tens to hundreds of thousands of dollars from paying out for unnecessary further treatment!

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Good point. I want to see it done. But some of the biggest centers here are still doing flow. Because I asked recently and I was told flow for my treatment protocol.

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From the Leukemia and Lymphoma Society MRD fact sheet, updated this year: lls.org/sites/default/files...

Chronic Lymphocytic Leukemia (CLL)

• MRD is detected by flow cytometry and PCR.

• Patients who remain MRD negative after the end of therapy for CLL may have better treatment outcomes.

• Patients who are MRD positive after the end of treatment may be candidates for treatment intensification, consolidation and maintenance strategies

I expect Next Generation Sequencing will eventually be added.

With respect to insurance cover: "Patients need to be aware that MRD testing may require prior authorization from an insurance provider." plus there's more about the involvement of out of network fees for specialist laboratories.

Our involvement as patients will be an important part of seeing MRD-U testing becoming increasingly used, so thanks for starting the ball rolling.

Neil

(I've also included the above reference in reply to your earlier question).

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The suggestion for patients, as I read it, is to become aware and knowledgable of as much as we can in regard to treatment.

It is not a burden on the Dr. nor does it cost anyone more (well, maybe time) to just make a statement to your Dr. " I have read about UMRD in regard to testing as patients are being treated to see how the CLL is being herded out of the system."

There is no pressure in that, and if the Dr. is worth his/her salt, he/she will be alerted to the fact that you are becoming educated about your disease and want to know how things are going. Many of us have found that we can build a relationship with the Dr., that the Dr. becomes more open and shares more, as we have learned a bit about CLL and can ask a question about our situation that says we have been researching, we have a support group and we hope to know how a given bit of information applies to our own CLL.

Granted, the Dr. may not be one who will converse with you on a one-to-one level. It is in those situation that patients who have the ability and opportunity to seek a second opinion, may want to do so.

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Yes agree 100% very thoughtful content. We cannot base anything from one meeting .

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I so agree with you !!!My husband depends on me to do the research, the questioning, and the worrying....he often tells the cancer clinic that he brought his staff. LOL At first, I think our doctor was surprised that I asked the questions that I did...that I knew about treatment plans, and asked about future treatments. Now, he laughs and asks me for my input and questions....we have established a respectable and warm relationship, which has helped with the healing of both my husband and me. I always remember what Dr. Brian Koffman said: " Smart Patients get smart care."....and I believe that smart doctors welcome the questions and the patients who participate in their own treatments. Dr. Koffman also recommended getting a team of around you to help in your treatment.....and making those connections.....he has a list that gave the CLL specialists in each country, and in the USA each state.....that is how we found our second opinion ---a researcher in Madison, WI

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