Tweet Chat Recap: Khan Discusses Current Treatment Options for CLL

Targeted Oncology was joined on Twitter by Cyrus M. Khan, MD, hematologist in the hematologist, Division of Hematology and Cellular Therapy at West Penn Hospital of Allegheny Health Network, for the discussion of a chronic lymphocytic leukemia (CLL) case.

Ahead of the discussion, Targeted Oncology followers shared their thoughts in a poll via Twitter and LinkedIn on what regimen they would be most likely to recommend for this patient. The majority of patients (75%) voted for venetoclax (Venclexta) plus anti-CD20 while treatment with a Bruton's tyrosine kinase (BTK) inhibitor with or without anti-CD20 or chemotherapy each received 12.5% of the votes.

Khan explains that he would most likely recommend a BTK inhibitor, especially a second-generation option such as acalabrutinib (Calquence), due to the fact that treatment is finite and can be stopped after just a year. Still, Khan agrees that both of the other options are viable and could provide benefit for this type of patient.

When treating this patient, Khan would keep in mind that using a monoclonal antibody with venetoclax would cause his patient to be at high-risk for contracting COVID-19 and could lead to complications. He notes it is important to keep in mind hypertension and the fact that BTK inhibitors can worsen it over time.

Further, Khan discussed the current standard of care treatment for patients with CLL and how in most cases, it consists of using targeted agents rather than chemotherapy. However, there is no definitive right or wrong answer when choosing between a BTK inhibitor and a venetoclax based regimen.

As there is still no cure for this disease, Khan explains that there is a need to develop more treatment options with a finite duration. Such therapies would not only benefit patients but reduce the financial burden on the healthcare system as a whole. He also notes that there is a need to learn more about minimal residual disease data and the sequencing of novel agents, as both remain in question.

In an interview with Targeted Oncology following the tweet chat, Khan discussed the emerging and recent data he thinks could influence the case we discussed.

What were your thoughts on the case we discussed?

It was a great case. Something that we see all the time in our practice is older patients with some comorbidities. Nowadays, we're met with many different options, and we try to formulate a plan that would fit onto that patient's specific profile and their wishes.

Getting different opinions is important, right? I mean, like I said, equally, as well as choosing one, target agents, while the other so I think just getting different opinions and thoughts about the same case can happen both in real time as a follow up, and then you can get different perspectives. I think it's a good idea.

What factors would influence your decisions and types of treatment that you would give to this patient?

I mean, of course, age is a factor in the risk factors as far as the genetic abnormalities of the CLL itself, as well as the comorbid conditions of the patient, all of those sort of play into our thinking on how to treat the patient. Also, logistical, and social issues, right, if a patient can travel back and forth, keep an eye on the lab, those kinds of things also play an important role. For example, there was a patient we had to treat recently. It doesn't happen often, but the patient doesn't even have a telephone, right? So that also we have to think about how to manage that situation. It's very different for every patient, we try to tailor treatments to each patient.

Can you discuss some of the up-and-coming research ongoing on the CLL space?

We have CAR T-cell therapy, which is chimeric antigen receptor therapy, and it's approved for various lymphomas but not yet for CLL. I think that is exciting for the future. We have our first patient in a month who I think we will be treating with our own homegrown CAR T-cell therapy here. Then, there's tumor infiltrating lymphocyte therapy that is also new. We have that trial open here as well.

Then proceed to Pirtobrutinib [L0X0-305], which is another BTK inhibitor that works even for patients who develop resistance to the current BTK therapy, so that's exciting. We also have various combinations of novel agents which will hopefully be used in a more definitive therapy of a finite duration rather than continuous therapy. I think all of these things are changing and in flux, and hopefully will improve and continue to prolong both the progression-free survival as well as overall survival for these patients.

How has the treatment landscape changed in the past decade?

Just 10 years ago, it was mostly chemotherapy. For the older patients, we were using FCR [fludarabine, cyclophosphamide, and rituximab [Rituxan]], for the younger patients we bendamustine [Bendeka] plus rituximab. Then for the more elderly, it was pyramidal cells, single agents, or even sometimes rituximab alone.

Now it's completely shifted. The role of chemotherapy has diminished for a minority of the patients, but for the most part, it's these targeted agents, whether it's BTK inhibitors, venetoclax-based regimens, newer monoclonal antibodies, other clinical trials, etc. So there has been a big shift.

What unmet needs still exist in this space?

The cure is still elusive. Obviously, we would like to cure patients. The other 1 would be the sequencing. We don't exactly know which target agents to use first, second, and third, because there's so many available agents right now for our use. Then it would be the cost of therapy because it is high. We'd like to reduce the cost of some of the treatments. We have to continue until progression of toxicity, so it would be nice to have more of a finite duration of treatment as well.

What excites you the most about the future of space?

All the research that's going into it excites me. There's CAR T-cell therapy, of course, there's trials for all the newer therapies. I think the most exciting thing is hopefully getting away from continuous therapy and going toward more definitive treatments with the combination of these targeted agents and achieving the same outcomes. I think it would be great.

For community oncologists, what is important to keep in mind when treating such patients?

One thing to keep in mind would be to always look for a clinical trial if there is one close because all these options have come from clinical trials. The second would be again to tailor treatment options to one’s patient's needs. All of these, whether it be a BTK inhibitor, venetoclax, various antibodies, etc., can be tailored to each patient and their own unique features.