Phillips Discusses Past Progress and Previews the Future in Hematologic Cancers

Tycel Phillips, MD

As the treatment paradigm for patients with hematologic malignancies continues to evolve, emphasizing clinical trial enrollment is a key factor to continue the advancements that have been observed across the space in recent years, according to Tycel Phillips, MD.

“We have clinical trials that are enrolling that will provide patients with opportunities to receive medications that they couldn’t technically get [otherwise],” Phillips said in an interview with OncLive^® following a State of the Science Summit™ on hematology, which he cochaired. “Clinical trial participation is very important to encourage, especially for these harder-to-treat diseases that we can’t cure. It allows us to move the field forward and allows for the improvement of the lives of patients.”

In the interview, Phillips, associate professor, Department of Hematology and Hematopoietic Cell Transplantation, Division of Lymphoma, at City of Hope, in Duarte, California, discussed presentations from his colleagues covering treatment updates and treatment trends across hematologic cancers, including non-Hodgkin lymphoma (NHL), myelofibrosis, and myelodysplastic syndrome (MDS).

OncLive:Your cochair, Alexey Danilov, MD, PhD, discussed BTK as a target in NHL, what has brought forth this new treatment wave?

Phillips: There are [multiple] drugs. One is the non-covalent BTK inhibitor pirtobrutinib [Jaypirca]. It has been shown to be much more efficacious in patients with chronic lymphocytic leukemia [CLL] than [those with] mantle cell lymphoma [MCL] because the mutational changes that covalent BTK inhibitors induce in [patients with] CLL are quite different from those induced in patients with MCL. Non-covalent drugs, which can overcome a site mutation, have been shown to be effective in CLL.

Another [class of] drugs are the BTK degraders. These agents have also been shown to be effective in patients with MCL who progress on the covalent and non-covalent BTK inhibitors. These drugs tag these receptors and target them for proteasome degradation, which eliminates the target vs blocking signaling down the pathway of the receptor. There are several companies who are exploring these drugs and there will be quite a bit of variation available when these drugs get approved.

[These drugs] have made an impact in CLL. Although they’re not curing patients with CLL, they have markedly extended [the time in which] we can shift patients from drug to drug and likely allow [most] patients with CLL to obtain a functional cure, where they die with the disease vs from the cancer.

Idoroenyi Amanam, MD, presented updates in myelofibrosis. What did you learn from this session?

There are some exciting treatments. I [also] found out that some of the drugs that we thought were exciting myelofibrosis have fallen by the wayside, such as the BCL-2 and BCL-XL inhibitor navitoclax.

[Investigators are] still making headway [and] there are several drugs that have been recently approved in myelofibrosis. Many of these are JAK/STAT inhibitors, which had been the mainstay of treatment. As we move forward with myelofibrosis [treatment], we’ll wait to see whether these newer drugs can continue to reverse some of the fibrosis and improve the marrow health of these patients and allow them to not need so many transfusions or other supportive care.

Brian Ball, MD, spoke on managing patients with MDS. What were your primary takeaways from this presentation?

[In terms of] the new agents that are approved in MDS, it was surprising to see how selective some of these drugs may be. MDS is a disease where the goal [of treatment] is to minimize some of the dysmorphic changes within the [bone] marrow and, more importantly, prevent transformation to acute leukemia.

Many of these drugs are slowing the tide of that transformation, which is the most [important] thing because when patients with MDS develop leukemia it is very hard to treat. Anything that can be done to delay or prevent that from happening is very important. A lot of these newer agents that have been approved, especially for certain subsets of these patients, are achieving those goals.

The takeaway for patients and providers is that there is optimism that we are slowly but surely trying to achieve our goal. We are extending survival in a lot of these incurable cancers. The goal is functional cure until we can [achieve] a real cure for these patients.

In the interview, Phillips, associate professor, Department of Hematology and Hematopoietic Cell Transplantation, Division of Lymphoma, at City of Hope, in Duarte, California, discussed presentations from his colleagues covering treatment updates and treatment trends across hematologic cancers, including non-Hodgkin lymphoma (NHL), myelofibrosis, and myelodysplastic syndrome (MDS).