Personalized Medicine Moving to Forefront of Hematologic Malignancies

Edward A. Stadtmauer, MD

While there are still several questions unanswered surrounding chimeric antigen receptor (CAR) T-cell therapy, the recent FDA approvals of tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (axi-cel; Yescarta) have led to a more promising outlook for patients with acute lymphoblastic leukemia (ALL) and non—Hodgkin lymphoma, respectively, as well as other hematologic malignancies down the line, according to Edward A. Stadtmauer, MD.

“This has been such an exciting time for the treatment of hematologic malignancies, particularly the immunotherapy approaches that have been developed,” said Stadtmauer, section chief of Hematologic Malignancies at Abramson Cancer Center at the University of Pennsylvania. “A lot of them have been, at least to a great extent, developed at the University of Pennsylvania, so it's been very exciting to be there for the last 5 to 10 years.”

OncLive^®: After 2 FDA approvals this year, what does the future hold for CAR T-cell therapy?

In an interview during the 2017 OncLive^® State of the Science Summit^TM on Hematologic Malignancies, Stadtmauer, who was also chair of the event, touched upon the future of CAR T-cell therapy, systemic therapeutic advances in the field of acute myeloid leukemia (AML), and remaining challenges in the multiple myeloma paradigm.Stadtmauer: The first FDA approval of a new cellular therapy was for children, or young adults, with ALL. These patients who have relapsed/refractory disease have very few options. We knew from the first patients we treated how effective this therapy could be, but we had to learn a lot about the potential toxicities and how to manage [them].

Over the last few years, we have become very successful, as evidenced by the approval of that agent in [August] 2017. It was really exciting to have this meeting since we recently got approval for a much larger potential group of patients in need—non-Hodgkin lymphoma (NHL)—which is one of the major success stories of all of medicine. However, when patients relapse, particularly if they become resistant to conventional therapies, it can [be] a very difficult prognosis.

What questions will we need to start answering regarding CAR T-cell therapy in the next few months?

Switching gears, what advancements in AML are you most excited about?

These cellular therapies, even in many subsets of [patients with] NHL, have had beautiful responses with very acceptable toxicities. Having these 2 new agents a part of all the other agents that we have is just going to tremendously improve the hopefulness and the outcome for our patients with hematologic malignancies.Which patients are the ones that we should really focus on for this therapy? Do you we give the treatment relatively early in the course of disease before they become sicklier and have more difficulty with tolerating therapies? Or, should we exhaust most of the therapies that we have already? Experience is going to help us answer that. No matter how good the clinical trials are that get us to this point of FDA approvals, we must think of this approach as so new and so novel that every patient that goes on these treatments is participating in a larger clinical trial to define what is the best treatment for these patients.As a myeloma specialist, I have been so thrilled over the last decade with the tremendous advances that we’ve seen in multiple myeloma and the hope in the outlook for patients with numerous new agents. Unfortunately, for our colleagues and the patients who have myeloid malignancies—particularly AML for the older patients and for patients who have relapsed disease—there has been very little progress, but not without trying. There have been a ton of attempts to come up with a new agent, but it's been very challenging in this patient population.

[However], over this last year, the physicians who care for patients who have AML had a major boost with a number of new agents that are helping the most challenging patients. These patients who are older and have a poor performance status have new agents that are likely to put them in remission and lead to long-term outcomes. The patients who have what used to be considered the poorest prognostic biology now have targeted therapies that are pills, are well tolerated, and are leading to great outcomes.

You specialize in myeloma, where there has been recent progress, as well. But what challenges remain?

Immunotherapy has been so helpful for our lymphoid malignancies. These targeted therapies that are focused on turning off the mutated enzymes [and] are leading to these cells proliferating are 2 prongs in a war against these diseases.In many ways, the most challenging aspect of multiple myeloma right now—we have so many good agents—is how to combine them properly and what sequence we should use them in. The clinical trials that are ongoing are starting to inform that.

It looks like combinations are better than single agents. A lot of the newer agents, when moved upfront or earlier in the disease course, seem to be leading to even better outcomes. There is still a lot to be done in myeloma even though we have a lot of agents, hope, and success with our patients. The next decade is going to look just as bright for them. In fact, the next major disease that we're going to probably have in these CAR T-cell therapies will also be for multiple myeloma, so it's an exciting time there, too.