Javier Pinilla, MD, PhD, Highlights MRD in Patient Care for a Variety of Blood Cancers

Javier Pinilla, MD, PhD, senior member and head of the lymphoma program, Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, Florida, discusses the importance of minimal residual disease (MRD) in patient care as well as its significance as a pivotal endpoint in clinical trials for new immunotherapies to treat a variety of blood cancers, including chronic lymphocytic leukemia (CLL).

Transcript

Hi there. My name is Dr. Javier Pinilla. I'm a hematologist at the H. Lee Moffitt Cancer Center in Tampa, Florida, where I lead the lymphoma group and I'm director of immunotherapy. In my clinic, I see chronic leukemia's, specifically chronic lymphoid leukemia's (CLL) as well as low-grade lymphomas.

MRD (minimal residual disease) is relatively new in the last couple of decades' as a way to measure disease when we don't see the disease itself. Thanks to new technologies, initially, hematologic malignancies, we have the incorporation of flow cytometry where the pathology, we see that we can count them.

Now, with the new technologies for molecular medicine, in this case, a PCR, we have that already for years in chronic myeloid leukemia. More recently, with the next-generation sequencing, we can detect very small amount of disease represented by these few cells that are still remaining in the body that can predict the time to next therapy or at least progression.

As well, we can follow patients over time in case we want to prevent or we want to see how the disease is going, even without seeing at the real level or the classical levels with PET scan or blood work.

There is no doubt that there are multiple targeted therapies that are coming specifically in CLL. We have, in the last year, incorporation of BTK inhibitors— reversible and irreversible. They are the ones who are coming to overcome some of the mutation.

However, the introduction already a few years of BCL-2 inhibitors have been a fundamental aspect of how we are improving outcomes in CLL patients, mainly referring to MRD and how MRD's now used in most of the clinical trials, if not most of them who are using venetoclax as part of the strategy to overcome or to eliminate as much disease as we have.

This is 1 of the 2 drugs revolutionized the treatment of CLL. We have these new immunotherapeutic strategies. We have the famous CAR-T cells also used in lymphomas and also in trials in CLL. More recently, we have the TRANSCEND data reported.

On those, once again, MRD with these next-generation sequencing technologies—like a ClonoSEQ that is the one approved—give us a fantastic way to see how these patients are doing. More recently, I will have to comment that biospecific monoclonal antibodies also target the B-cells, as well as the P cell immune system are getting a lot of attention because they are off-the-shelf. They're readily available. I think we're going to see very interesting data in the next meetings

We have some updates on the BTK inhibitors trials with long-term follow ups . I would say that maybe the new thing was the GLOW study that compared the new combination of BTK, in this case, ibrutinib, with venetoclax against standard-of-care obinutuzumab/chlorambucil.

Some trial that, in my opinion, is important because it's going to hopefully will bring this first approval of 2 oral or dual oral target therapy for the treatment of CLL with the goal to try to get undetectable or minimal residual disease at the best levels so we can make our patient have limited therapy but a long potential to have long period of time with no therapy.

This data already presented, so I think the question, “What are we going to see in ASH?”

It still is a mystery. For sure, we're looking forward to see the updates of irreversible inhibitors. I think we're going to see very interesting data on pirtobrutinib.

I'm sure we're going to receive data of a biospecific monoclonal antibody. For sure, we're going to see updates of these doublets, triplet's trial that are being ongoing, combining BTK, BCL-2 inhibitors, as well monoclonal antibodies in a different way.

Most of them, all these trials have been done and incorporate MRD as a way to perform these trials. Patients get therapy until they go MRD. They stratify, they use MRD, and we're going to see much more data in this next meeting of ASH coming in December.