Bringing Cancer Care Closer to Home

Patients with cancer face many challenges following diagnosis, and one obstacle that can mean the difference in receiving a lifesaving treatment is location of care. Baylor Scott & White Oncology Program is changing this by bringing the best treatment possible closer to home at its facilities in North and Central Texas.

Its clinical trials stand out among the hematology program, in which the latest treatments are being studied to advance the care of patients with blood cancers.

Throughout the system, there is supportive help through social work and, most recently, a revamped survivorship program to guide people on how to put their lives back together after cancer.

In an interview with CURE®, M. Yair Levy, M.D., who oversees clinical research hematologic malignancies in the North, and Mark Holguin, M.D., in Central Texas, discussed the program and new, promising treatments.

Can you please tell us about the hematology program at Baylor Scott & White Health?

Holguin: Our system has been integrating the oncology services of Baylor Healthcare in North Texas and Scott & White Healthcare in Central Texas since the merger in 2014. Baylor has always had a strong networked oncology program, with Dr. Levy ably leading the hematologic malignancy clinical research efforts at its flagship facility, Baylor University Medical Center in Dallas.

In Central Texas, there is also a network of clinics with our flagship facility in Temple, Texas, and our hematologic malignancy clinical study program led by Dr. Vinit Karur. Since the merger, we have worked to bring these two groups together.

We have a joint membership with the Southwest Oncology Group, which is a National Cancer Institute program that helps to bring clinical trials to large numbers of institutions across our country. We have developed a common (institutional review board) process to permit studies to be shared across the system. We have shared conferences and tumor boards to facilitate sharing of interests and studies across our system Both institutions have had clinical trials programs for years. As researchers, we are interested in trying to develop the new therapies that are coming along and to help bring those new agents out, get them tested and push the field forward to the best therapy for our patients.

You mentioned new agents. Can you discuss these?

Holguin: There are a wealth of new agents being tested, and there is great optimism for treatment of cancers that up until now have not had good options.

Acute myeloid leukemia (AML) is an area in which we are happy to see new treatments being developed. For over 30 years, we have relied on an aggressive chemotherapy regimen that severely affects blood production, requiring about four weeks in the hospital to deliver that treatment support with blood transfusions and treatment for infections until blood counts recover. Our chances for cure in the adult population were only in the 30 to 50 percent range.

In the past year, a new agent called Rydapt (midostaurin) has been studied and approved. This is an agent that helps us target a chromosomal change that we have known is common in AML. Changes in the FLT3 gene occur in approximately 30 percent of adult AML cases and confer a worse prognosis. The addition of Rydapt to standard chemotherapy in patients with AML having certain FLT3 mutations has led to improved cure rates. This has spurred further interest in targeted therapies that target other known AML mutations to enhance treatment for more patients with AML.

Levy: Even though Rydapt was first to market, it will soon face intense competition from gilteritinib, quizartinib and crenolanib. These are newer FLT3 inhibitors that may provide more complete FLT3 inhibition, with more specificity for the target and perhaps better tolerability.

What advances in blood cancer most excite you?

Levy: In AML, there has recently been an approval for Vyxeos (CPX-351). We participated in the study of this drug. It looked at people ages 60 to 75 with either secondary acute leukemia or leukemia with genetic changes suggestive of either chemotherapy as the cause or the emergence from myelodysplastic syndrome. They used the same drugs that we typically use in our induction called 7-plus-3.

They found a synergistic ratio of 5-1 with the cytarabine to the daunorubicin. And the reason it’s interesting is that for the past several decades, people have looked at various combinations of these drugs and various dosing, but they weren’t able to demonstrate a survival benefit. These researchers did demonstrate a survival benefit.

This validates their delivery platform and the importance of drug ratios. That is significant because most of the treatments that we use in oncology are drug combinations. We do that because we know if we use multiple different drugs, we are able to overcome some resistance that can occur in the cancer cells.

This platform shows that how we administer therapies matters. It’s a great platform for optimizing current combinations of therapies.

In addition, Idhifa (enasidenib), an IDH2 inhibitor, was approved. IDH2 is a mutation that occurs in a fraction of patients with AML. This is a drug that inhibits this pathway, providing these cells with a survival advantage. The response rates were impressive enough to earn an approval from the Food and Drug Administration (FDA) on early-phase data.

Also, Mylotarg (gemtuzumab ozogamicin) was recently re-approved. This is an antibody with an attached chemotherapy payload, functioning like a smart bomb that targets the leukemia cells directly. The Oncologic Drug Advisory Committee, which provides recommendations to the FDA, ruled in favor of it following a phase 3 trial that showed a progression-free survival benefit. Mylotarg was a drug previously on the market in the United States, but it was withdrawn because of toxicity.

Immunotherapy has become a huge area of interest. What lies ahead in this treatment?

Holguin: For decades, there has been hope that we could somehow modify or support the body’s own immune system to recognize cancer cells as foreign and destroy them using our own body without having to add to toxic agents. This has been steadily developing, and in the past couple of years, there seems to have been an explosion.

There are different techniques for this. The first techniques were to use antibodies that could be directed against proteins that live on the surface of cancer cells that would help the immune system recognize those cells and get rid of them. Rituxan (rituximab) was one of the first and most successful antibodies that helped us to find a protein on the surface of many lymphoma cells. It has revolutionized treatment for B-cell lymphomas.

More recently, we now have monoclonal antibodies directed against other proteins that are active in Hodgkin lymphoma. An agent known as Adcetris (brentuximab) is an antibody that is coupled with a toxin that will bind to the CD30 protein. This has provided an option for relapsed Hodgkin disease and is effective as maintenance therapy after highdose chemotherapy.

Although AML comprises the majority of acute leukemia in adults, a significant minority can develop acute lymphoid leukemia (ALL). Patients who do not respond or relapse after initial chemotherapy have not had many options outside allogeneic bone marrow transplantation. Recently, a new bispecific antibody has been developed that can bind to CD19 on ALL cells and can also bind to CD3 on normal T cells of the immune system. This double-ended antibody allows the immune system to target ALL cells more effectively and has shown improved survival for relapsed and refractory patients with ALL. Multiple myeloma has also benefited from monoclonal antibody therapy development. The most exciting is Darzalex (daratumumab), which targets the CD38 protein on the surface of myeloma plasma cells.

Finally, chimeric antigen receptor T-cell therapy, or CAR-T cell therapy, has shown remarkable responses in patients with a variety of hematologic malignancies including ALL, chronic lymphocytic leukemia, lymphomas and myeloma.

What are some of the biggest concerns that patients have about clinical trials?

Levy: Anytime people enter a clinical trial, they are concerned about being on a placebo — an inactive treatment — controlled study, but those are quite rare in oncology trials, and all treatment arms should at least contain what would be considered a standard treatment.

I explain to patients that every clinical trial is an experiment, but it is a controlled experiment with known parameters. A physician’s job is educating patients on their disease and treatment options. We explain standard-of-care options as well as clinical trials (when applicable).

My bias, as a researcher, is to enroll patients in studies that seem promising and applicable to their situation. We have participated in many studies that have led to approved therapies (including all the drugs mentioned in this article), which allowed patients to be treated with these new treatments before they were commercially available. The only way to get better treatment is to continue trying novel approaches.

M. YAIR LEVY, M.D., is a physician on the medical staff at Baylor University Medical Center at Dallas, where he serves as the medical director of the Blood Cancer Research and Treatment Center. The center specializes in advanced research and the latest treatments in hematologic malignancies, including acute leukemia, lymphoma and myeloma.MARK HOLGUIN, M.D., is a medical oncologist on the staff of the Scott & White Medical Center in Temple. He is the director for the Division of Hematology/Oncology at Scott & White and is a clinical associate professor of medicine at the Texas A&M Health Science Center College of Medicine.