Tag Archive for: molecular profile

CLL Clinical Trials for Molecularly Defined Patient Subgroups

CLL Clinical Trials for Molecularly Defined Patient Subgroups from Patient Empowerment Network on Vimeo.

What’s the latest in chronic lymphocytic leukemia (CLL) clinical trials for molecularly defined patient subgroups? Experts Dr. Jennifer Brown from Dana-Farber Cancer Institute and Dr. Callie Coombs from the University of California, Irvine discuss research updates for CLL patient subgroups, resistance mutations, and drug intolerance.

Download Resource Guide  | Descargar guía de recursos

See More from EPEP CLL

Related Resources:

How Can CLL HCPs Gain More Understanding of Mutation Profiles

How Can CLL HCPs Gain More Understanding of Mutation Profiles?

CLL Expert Updates on Diagnostic Tool and Technology Advances

CLL Expert Updates on Diagnostic Tool and Technology Advances

Managing CLL Side Effects | Innovative Strategies and Approaches

Managing CLL Side Effects | Innovative Strategies and Approaches

Transcript:

Dr. Nicole Rochester:

So now we’re going to shift to talking about clinical trials and novel targets focused on molecularly defined patient subgroups. We know that by understanding the molecular profile of a patient’s CLL, that oncologists can choose the most effective therapies. So, Dr. Brown, I’m going to start with you for this one. Can you talk about any emerging CLL trials targeting specific molecular subgroups, and also how can CLL experts stay updated on these advancements in clinical trials?

Dr. Jennifer Brown:

So, as you heard from Dr. Coombs, there’s increasing interest in looking at high-risk patients in particular, and I think looking specifically at patients with p53 aberration in dedicated clinical trials, it’s become increasingly clear that the behavior of the disease when it’s higher risk based on p53 mutation, NOTCH mutation, IGHV status is quite different, particularly with time limited therapy compared to lower risk disease. And so having dedicated trials that evaluate outcomes specifically in certain of these subgroups is increasingly important. We do have more trials than we used to focusing specifically on p53 aberration.

My personal belief is that we would be well served to have trials separately in the IGHV groups that Dr. Coombs mentioned, although that has not gained as much traction. And then what we are seeing is now that there are resistance mutations, it actually has turned out that some of the drugs that we use in that setting, venetoclax (Venclexa) and pirtobrutinib (Jaypirca), seem to have pretty similar activity in patients with and without the mutations. But as drugs are being studied in this context, there’s been an increasing tendency to study them in specific subgroups.

So patients who have the mutation and had clinical progression on a covalent inhibitor, patients who don’t have the mutation and had clinical progression, patients who may have come off their covalent inhibitor for adverse events who may not actually be resistant, what is their response to the next line of therapy? And so all of that is just helping us understand in a more nuanced way what the best benefit for patients will be as we look at these different subgroups of patients.

Dr. Nicole Rochester:

Thank you, Dr. Brown. Appreciate that. Dr. Coombs, do you have anything to add?

Dr. Callie Coombs:

Yeah, so I echo all of Dr. Brown’s comments, and I think I’m the person that is bringing all the practical aspects of CLL care because it’s, she’s so thorough. I just always like to contribute a few little pearls. So, pirtobrutinib has been an exciting drug, to see it become available for our double refractory patients. So the current FDA indication is for patients failed by not only a covalent BTKi but also venetoclax. But it’s the first BTK inhibitor that we can effectively use in the setting of a prior BTK inhibitor.

And that’s because of this unique aspect where instead of forming a covalent bond at the C481 residue, it binds reversibly, and we can still see activity. But the practical aspect is that that’s not an effective strategy when you have a patient progressing on, say, ibrutinib (Imbruvica), you can’t switch them to acalabrutinib (Calquence) or zanubrutinib (Brukinsa) because of their shared mechanism of resistance. They’re all covalent inhibitors. They all share the same mechanism of resistance.

And so that’s one thing I’d like to bring up. However, there’s a very different and very common clinical situation that I encounter really a lot in my clinic, which is intolerance. And so that’s where it would be a very effective strategy to switch a patient from one covalent drug to another. And so literally in the past couple weeks of clinic, I’ve had patients with chronic long-standing toxicities to ibrutinib (Imbruvica) that perhaps went underrecognized where I say, “Hey, you’ve had…notice your blood pressure has gone up a lot.

Let’s switch you over to acalabrutinib,” or other patients, “Oh, you’ve had issues with atrial fibrillation, it…let’s try switching you to zanubrutinib.” Because the rates are a lot lower and a lot of patients can have improvement or just complete resolution of the prior side effect. And so I hope that that emphasizes this is something that we think about every day, and switching is appropriate in the setting of intolerance. It’s not appropriate when you’re staying in the covalent class to switch in the setting of progression. But pirtobrutinib being a non-covalent inhibitor is certainly very effective after a covalent. And I think once we see readout of some of the ongoing Phase III trials, we may be able to use it in that setting under an approved FDA label, though that is to be seen in the future.


Share Your Feedback

Navigating Lung Cancer Biomarker Testing | Challenges and Solutions for Timely Access

Navigating Lung Cancer Biomarker Testing | Challenges and Solutions for Timely Access from Patient Empowerment Network on Vimeo.

To achieve accurate biomarker data for lung cancer patients, what are challenges and solutions? Expert Dr. Joshua Sabari from NYU Langone discusses challenges that can arise during the biomarker testing process, solutions to overcome the challenges, and proactive advice to help ensure optimal patient care. 

[ACT]IVATION TIP

“…not only know your mutation, but speak up for yourself. Speak up for your loved one. Make sure that the correct testing is done and that there is sufficient tissue, both for blood and tissue from the biopsy, to do the correct testing to allow us to potentially match people to the best treatments available.”

Download Resource Guide  | Descargar guía de recursos

See More from [ACT]IVATED NSCLC Biomarkers

Related Resources:

Understanding Non-Small Cell Lung Cancer: Types, Biomarkers, and Treatment Insights

Understanding Non-Small Cell Lung Cancer: Types, Biomarkers, and Treatment Insights

When Should Lung Cancer Patients Receive Biomarker Testing?

When Should Lung Cancer Patients Receive Biomarker Testing?

Equity in Action | Addressing Biomarker Disparities in Lung Cancer

Equity in Action | Addressing Biomarker Disparities in Lung Cancer

Transcript:

Lisa Hatfield:

So, Dr. Sabari, this is a multi-part question here, so I’ll break it down a little bit. What are some of the main challenges in collecting accurate biomarker data, and how can researchers overcome these challenges? And considering the challenges that oncologists face in retrieving testing results at second-line treatment, what technological advancements or procedural changes could streamline the process and ensure timely access to biomarker testing results?

Dr. Joshua Sabari:

So when we talk about biomarker testing, we’re generally talking about testing the tissue, as well as sometimes testing blood or plasma. And it’s important that if you have a good and accurate biopsy with sufficient tissue, that then gives us the ability to select or do the correct biomarker testing. So that’s first and foremost, you know, fine needle aspiration, small aspirations may give us insufficient tissue. You know, whereas if you do a core needle biopsy, whether it be percutaneous through the chest with an image or bronchoscopically through the mouth with a camera, we’re able to get a large sample of tissue.

This will give us the amount of tissue needed to do the correct biomarker testing. We call it next generation sequencing or short for NGS, where we’re able to actually identify the mutations or abnormalities in your DNA. The other type of test we can do is on plasma, where we sometimes call it a liquid biopsy. That’s a simple blood test where, you know, a team will draw about two 10 cc blood tubes, where we’re then able to sequence, you know, DNA in your blood to help identify these alterations.

So having sufficient tissue or having the blood drawn, that’s important. 

But then also having your physician and your clinician and healthcare team order the appropriate test. You know, it’s unfortunate. A lot of folks that I see in my practice have not had adequate testing done in the frontline setting. Oftentimes, clinicians will be in a rush to start systemic treatment, both because patients are symptomatic, but also because they want to get going with treatment for patients. So, you know, stopping your physician, your team and saying, hey, what is my mutational profile? What is my mutational status is an extremely important discussion to have with your clinician. So a lot of times we only see this being done in the second-line setting.

So having that information up front could allow you and your family members to be matched to the best possible therapy. Now, if you’ve started a treatment and you don’t have genetic testing or molecular testing done in the front line, I would then have it done in the second-line setting. So one of my activation tips here is not only know your mutation, but speak up for yourself. Speak up for your loved one. Make sure that the correct testing is done and that there is sufficient tissue, both for blood and tissue from the biopsy, to do the correct testing to allow us to potentially match people to the best treatments available.


Share Your Feedback

Create your own user feedback survey

Expert Perspective | Key Advice for AML Patients

Expert Perspective | Key Advice for AML Patients from Patient Empowerment Network on Vimeo.

Facing an AML diagnosis can feel overwhelming. Dr. Omer Jamy shares tips for newly diagnosed AML patients, emphasizing the importance of a consultation with a specialist.

Dr. Omer Jamy is a Leukemia and Bone Marrow Transplant Physician and Assistant Professor at the University of Alabama at Birmingham. Learn more about Dr. Omer Jamy.

See More from Thrive AML

Related Resources:

Updates in AML Treatment and Research From ASCO 2023

What Are the Phases of AML Therapy


Transcript:

Katherine Banwell:

Dr. Jamy, for patients who have been diagnosed with AML, could you share three key pieces of advice for them. How can they be proactive in their care? 

Dr. Omer Jamy:

Sure. So, I feel like as a leukemia physician I would like to see, just to give you an example, I’d like to see all the leukemia patients in Alabama. But that’s not feasible, right? But what I would recommend to patients and caregivers is that wherever they are diagnosed, I do feel that they would benefit from a consultation with a leukemia physician at a tertiary care center or an academic center. And they would benefit due to various reasons, right? So, the first reason would be that as a leukemia physician my job is to just keep myself upgraded with leukemia care, leukemia management.  

So, one aspect of leukemia is therapeutics, right? So, drugs that are approved, easy to give. But the other aspect is understanding the biology of the disease, understanding how leukemia is going to behave. To get a better profile for AML for a patient. So, in a way saying that not all AML cases are the same. So, to be seen at a center would help the physician understand the unique cytogenetic or molecular profile of that patient’s AML which may be different from the next patient’s AML which could mean that the treatment algorithm for one person might be slightly different from the second person. So, I mean the academic and the people working at academic centers cannot survive without people working in the community, so it goes hand in hand. So, I feel like co-management of a patient with AML is extremely important. I feel like things will not get missed that way.  

I feel like the treatment plan, no matter where it is implemented, would really benefit the patient. It can be implemented closer to home as long as it’s been co-managed with someone closer to home as well as someone at the center where they have access to more information. What this would also help is get the person and the family plugged into a system where, let’s say if therapy wasn’t working, they’d have access to enroll on clinical trials down the line as well. Which unfortunately are only present at academic centers and not very widely available, especially for blood cancers. There may be trials for solid tumors easily conducted outside of academic centers, but unfortunately that’s not the case for blood cancers, specifically AML. So, the opportunity to enroll in clinical trials will also help.  

And then lastly, I feel like it’s our ability to offer bone marrow transplant to older patients has improved over the past 10 to 15 years.  

We’ve become better in identifying donors and in identifying patients, getting them ready for transplant that I feel that a person and the caregiver should inquire from their physician about the opportunity – oh, of No. 1 the need for transplant for the leukemia is because not all the AML patients may benefit from our transplant, but most of them do. And definitely anyone who relapses would benefit from a stem cell transplant.  

So, I feel like inquiring about that is very important because to get plugged in at a transplant center early on is important because you don’t want to waste time early on. You may not need the transplant, but just having the consultation and just having a preliminary donor search ongoing in the background is really helpful because when the time comes that a person needs the transplant, then you’ve already got some of that information ready, and you can proceed quickly. So, I feel like a few of those things might be helpful which I try to educate in the community as well and do outreach.  

Because I feel like it’s important to let people know that AML is an aggressive disease. Transplant is pretty intense, but we are now making it more and more tolerable for older patients.