Management of CML: New Agents and Monitoring for MRD

At the 2022 Lymphoma, Leukemia & Myeloma Congress, Ehab Atallah, MD, Medical College of Wisconsin, Milwaukee, provides an update on the management of patients with chronic myeloid leukemia (CML), highlighting new available agents and the role of monitoring for minimal residual disease (MRD).

Transcript:

Hello everyone. I'm Ehab Atallah from the Medical College of Wisconsin. I'm at the 2022 Lymphoma, Leukemia, and Myeloma Congress in New York. My talk today is about [chronic myeloid leukemia] CML and new drugs in CML. I’ll also talk a little bit about monitoring.

First of all, do we really need new drugs in CML? And I would argue yes, because we know that the survival for our patients with CML is still less than the general population. Patients who need to stay on these drugs continue to have issues with their quality of life. And we also know from patients that they really do want the cure. They don't want to take pills forever. 

We do have several studies going on and a new drug that was just approved. The new drug that was just approved is asciminib, which was approved a few months ago. And asciminib has shown activity in patients who have had more than 2 drugs, and in patients with a T315I mutation. Overall, it seems to be pretty well tolerated with side effects, mainly related to gastrointestinal upset, headache, and some cytopenias and elevation in lipids. This approval was based on a randomized trial known as the ASCEMBL trial where patients were randomized to asciminib or bosutinib. And the responses with asciminib were about 15% to 20% different than bosutinib in this patient population. We do have other TKIs that are currently in clinical trials, olverembatinib and vodobatinib. And other than the TKIs, we're also investigating other mechanisms to cure patients with CML, including ruxolitinib, an MDM2 inhibitor and PD-1 inhibitors. In summary, looking at improving the treatment for CML, we are looking at newer TKIs, one of them is already FDA approved. And we're also looking at adding other drugs to the TKI in order to improve these responses.

The second part we'll talk about monitoring. Monitoring for CML is really straight-forward based on guidelines, it is mainly done through peripheral blood PCRs. And the response really depends on how deep the response is and how long has the patient been on treatment. If you're on treatment for 3, 6, 12 months, how deep should the response be in PCR? We only recommend a bone marrow if someone is not responding well. But if patients are responding well, peripheral blood PCR is great for monitoring.

The other important part to know about monitoring is in patients who are TFR, or treatment-free remission. These are patients who have been on-drug for at least 3 years and have had a deep response for at least 2 years. Those patients can attempt stopping drug. And if we choose to stop drug in those patients, their monitoring is different than if they're on-drug. If they're eligible and they choose to stop, then we would monitor them monthly for the first 6 months, every 2 months for 6 to 12 months after that, and then every 3 months forever.

The reason that monitoring is so close in the first 6 months is that most relapses happen in these first 6 months. Then, we need to continue monitoring them forever, because there have been reports, in a very small percentage of patients, of late relapses. So therefore, PCR monitoring really needs to essentially continue forever. 

In summary, for CML, we do need better therapies. We need to cure patients. And cure means that we get patients off-drug and they don't have any evidence of disease. And we need to monitor patients closely. And it's different when we're monitoring patients on-drug as opposed to when they're attempting treatment-free remission. Thank you for listening.

Source:

Atallah E. 2022 Update on Management of CML: New Agents and Monitoring for MRD. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-22, 2022. New York, NY.