Mato Highlights Promise of Investigational Immunotherapeutics in CLL

Anthony R. Mato, MD, MSCE

The promise of immunotherapy in the form of anti-CD20 antibodies, checkpoint inhibitors, and CAR T-cell therapies in patients with chronic lymphocytic leukemia (CLL) cannot be denied, according to Anthony R. Mato, MD, MSCE; however, many of these approaches remain investigational and more data are needed before more options can be added to the treatment arsenal.

“What we are learning from other malignancies is that the immune system is key to achieving long-term disease control,” said Mato. “Restoring immunity to patients with CLL [through the use of immunotherapies] should help to produce that same outcome.”

In an interview with OncLive, Mato, hematologic oncologist and director of the CLL Program at Memorial Sloan Kettering Cancer Center, discussed the different research efforts that are being made with immunotherapy in CLL.

OncLive: Could you provide an overview of immunotherapy in CLL treatment?

Mato: Immunotherapy is a bit of a loose term in CLL. The first immunotherapy for CLL was allogeneic stem cell transplantation. The word “immunotherapy” really means anything that augments the immune system to treat a disease or help the immune system to treat a disease. We have several potential immunotherapies in CLL. For example, CAR T-cell therapies are another way that we can utilize the immune system [to fight the cancer]. Even antibodies, such as anti-CD20 antibodies, can help flag abnormal cells for destruction by using the immune system as one of the mechanisms of action. Immune checkpoint inhibitors can activate T-cells and other cells. We also have bispecific antibodies. All these approaches, with the exception of the anti-CD20 antibodies, are still experimental therapies in CLL, but they have a promising future.

What is some of the work that is being done with CAR T-cell therapy in this disease?

CAR T-cell therapies are not a standard of care for patients with CLL. These products are not yet FDA approved [for use in this space]; they are really only used as an experimental therapy. These T cells are genetically engineered to be directed specifically against the cell surface marker CD19. Very small series at academic medical centers have demonstrated promising data and activity for these cells, [alone] or [in] combination [with] small molecule drugs like ibrutinib (Imbruvica). CAR T-cell therapies may have a future in CLL in [that they may be] used particularly where transplant had been previously thought to be used. However, it remains to be seen how these active cells will be brought into the overall sequencing strategy for patients with CLL and whether or not they will represent a paradigm shift.

Larger series, more data that are generalizable to practices, and the ability to develop these cells and utilize them as more of an off-the-shelf type of product are all the things that we need to see to help make these products more widely available for our patients. With that being said, the general concept of utilizing the immune system and activating it to kill cancer, is very impressive. The major competing factor in CLL is that we have had so many wonderful molecules that have been developed that are active and have already been demonstrated to prolong survival. It is a crowded space, but I do believe they will fit in; at this time, I’m just not sure who will be the best candidates for this approach and in what line of therapy this should be used.

What are your thoughts on the use of biosimilars in this space?

I have not yet used a biosimilar in the management of my patients with CLL. The potential with biosimilars is that they may become more widely available for patients. Clinically, we have limited prospective information on how these drugs perform in patients with similar diseases. It remains to be seen. We will probably need real-world studies to confirm how these drugs perform for patients in clinical practice. Theoretically, they should be the same drug [as the reference product] and, as such, we should see similar outcomes. However, as someone who is relatively new to the idea of using a biosimilar, I am as inexperienced as everyone else.