American Society Hematology 62nd Annual Meeting and Exposition
Friday, Dec. 4th Satellite Symposia
This year is unusual in so many ways, with all of the meetings being virtually, yet much of the content being broadcast live.
Here are my quick notes from what is really day -1 of ASH.
The Friday before the official 62nd American Society of Hematology (ASH) Annual Meeting and Exposition starts with a packed schedule very early on Saturday. Here is my brief summary.
Friday was full of educational symposia that are learning opportunities across the spectrum of benign and malignant hematology.
The structure of all the sessions are all pretty similar, and are primarily case based.
All involve top experts presenting cutting-edge information with pre-recorded slides, panel discussions, followed by live Q+A.
Since a news embargo is in place until the minute the oral presentation and posters go live online, the faculty can only broadly hint as to what is coming. But seeing as the faculty of these symposia are frequently the very same folks who are doing the research, we can often get some idea of what is to come.
This year CLL, as in most years, was well represented.
There were four symposiums which were of course overlapping on the schedule. I attended the maximum amount that I possibly could, which was two.
- Mapping the New Era in CLL Management: Precision Medicine and Patient Perspectives in Treatment-Naïve and Relapsed Disease (90 minutes+)
This activity was excellent and was co-sponsored by the CLL Society (CLLS) and PeerView Institute. CLLS was featured as the most robust and reliable resource for patient information. Terry Evans very capably brought the patient perspective to multiple clinical scenarios. Most of the physician faculty are well known by the frequent visitors to our website.
There was no way to see how many were in attendance. But in the old days of live events, there would have been several hundred or more.
- Addressing the Medical Need in CLL: How BTK Inhibitors Are Improving Outcomes (2 hours+)
This session featured three members of the CLLS Medical Advisory Board: Drs. Ian Flinn, Susan O’Brien and John Pagel. Needless to say, it was full of great information and linked to resources that Clinical Care Options (CCO) and CLLS co-developed to educate community hematologists.
Also, I was able to catch portions of the other two overlapping sessions:
- Clinical Advances in Immune Thrombocytopenia: Integrating New Therapies
This presentation focused on secondary immune thrombocytopenic purpura (ITP) as it is a dangerous and fortunately, rare, complication of CLL. Simply put, ITP is a condition where our own immune systems destroy our platelets, leading to the risk of severe bleeding. ITP repeatedly threatened my life early on in my disease. Thankfully, it has been dormant for many years now.
- Taking Action with Minimal Residual Disease (MRD): Technique, Role, and Utilization of MRD to Improve Outcomes in Patients with Hematologic Malignancies
The portion of the three-hour session that I listened in on included Dr. Nitin Jain leading a discussion on minimum residual disease (MRD) in CLL.
If I have time (and if they are archived for later viewing) I will try to catch the other overlapping CLL sessions that featured top doctors, including members of the CLL Society’s Medical Advisory Board.
Overall, I am so excited to see that the patient is increasingly being recognized as part of the care team, but also being utilized to educate the physicians. Seems like this should be a no-brainer, but unfortunately, it is not. In fact, it is quite revolutionary in some hematology circles, and I am very proud of our role in this revolutionary shift.
These sessions are all free, and you don’t need to have registered for the ASH meeting to watch them. At a later date, we will provide the links and share what slides we can. But please keep in mind, these presentations are aimed at a professional healthcare audience.
Now that the scene has been set, let me share some of the actual take-aways and learning points from Friday. I will not be pausing to explain all the words and acronyms as tomorrow starts very early.
Let’s go through some key highlights that were both lessons from today and teasers for what is to come.
Our own Terry Evans, CLL Society’s Support Group Director and Dr. John Gribben both argued persuasively about the importance of involving the patient in the decision-making process.
As an example, for the 11% of CLL patients that are fit, less than 70 years old, and have favorable markers (including IgHV-Mutated and normal TP53) who need treatment, the physician should discuss the option of six months of FCR. FCR is a potent chemotherapy immunotherapy (CIT) with which 50.7% of patients who are IgHV-Mutated achieve MRD-negativity (uMRD) post-treatment. Of these, PFS (progression free survival) was 79.8% at 12.8 years. A plateau was seen on the PFS curve in patients who are IGHV-Mutated, with no relapses beyond 10.4 years in 42 patients.
Physicians should discuss this treatment option where it might make sense for that one out of nine CLL patients with the most favorable prognostic markers, but not with the other eight patients. And they should ask the patients what they want.
Does the patient want to avoid chemo at all costs, do they want a limited duration therapy, or do they feel comfortable taking a medication every day? The only way to know is to ask.
We know that Ibrutinib works best when used up front. That data will be soon be updated.
We know that ibrutinib discontinuation rate at 5 years was:
- Frontline: 41%
- R/R: 53.7%
We know about 85% of patients who are intolerant to ibrutinib can resume therapy with acalabrutinib.
We know that acalabrutinib cannot be taken by folks who need a proton pump inhibitor for excess acid problems. That is not the case with ibrutinib or zanabrutinib (approved for mantle cell lymphoma, but not for CLL, yet).
We know that ibrutinib works well on 11q deleted patients, unlike CIT.
We know that it also works on deletion (del) 17p where CIT has no role. But in the R/R (relapsed/refractory) patients, responses are less durable, and the median time to progression is 26 months in del 17p patients. Though 17% of those high-risk patients have still not progressed at seven years.
We have long known that there is no role for CIT in second-line therapies.
We know in a small study of 17 patients who were intolerant to ibrutinib, 16 could take zanabrutinib.
We know that ibrutinib works for patients who fail venetoclax frontline, and vice versa, that venetoclax works well for those who fail ibrutinib.
We know that the majority of ibrutinib, acalabrutinib or zanabrutinib failure is due to the mutation of the binding site (C481) that prevents co-valent binding. But newer BTKis such as ARQ-531 and LOXO-305 can work because they bind differently. We know there will be no more data on LOXO-305 presented.
We know that the likelihood of a patient having mutations that confer resistance to both venetoclax and ibrutinib is extremely low, thus explaining the high response rates in the Captivate trial that offer those 2 drugs in combination. It will be updated at ASH 2020.
We know that those who achieve undetectable MRD (uMRD or MRD negative) with a venetoclax-based therapy, do very well, with very durable remissions, but we do not know what to do for those who don’t.
We know there is a high correlation (93%) between blood and bone marrow MRD findings, so that may mean fewer bone marrow biopsies in the future.
We know that while MRD testing is only now entering the clinic, it is increasingly being studied as a meaningful, clinically relevant end point in trials. More on this coming too in the next few days.
We know that the CAR-T liso-cel works well on CLL patients that have run out of options, and that ibrutinib seems to lower the incidence and severity of CRS (cytokine release syndrome) and improve outcomes. These data too will be updated.
We know that for those with CLL induced secondary ITP, the usual best course of action is to treat the ITP if the CLL is not raging, and not to treat the CLL. And we know that steroid use for ITP management should not be prolonged beyond 6 weeks or so.
We know that many exciting new drugs and new drug combinations are coming.
We know that the future looks bright.
And that is just a quick brain dump from day minus one before all the real news starts rolling in. Check in with us daily. We will be posting updates. Later we will interview the researchers, explain the terminology, and fill in the gaps.
Stay tuned. Stay strong. We are in this together.
Brian Koffman MD (retired)
