The Current State of Hematologic Malignancies

A Conversation With Carl Freter, MD, PhD

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Carl Freter, MD, PhD

Our advancing technology and electronic learning systems will exponentially evolve, giving us tools we can only dream of. But I’m a bit old-fashioned and a huge believer in the personal touch of oncology, creating a bond between physician and patient.

—Carl E. Freter, MD, PhD

Due in part to the refinement of bone marrow transplantation and its many innovations, some leukemias that once were death sentences now have cure rates of up to 90%. As research in transplantation and other promising areas accelerates, we are on the verge of breaking new clinical boundaries in blood cancers.

To shed light on the current state of hematologic malignancies, The ASCO Post recently spoke with Carl E. Freter, MD, PhD, FACP, Professor and Director of the Division of Hematology/Oncology and Bone Marrow and Stem Cell Transplantation, Saint Louis University School of Medicine (SLU), and Associate Director and Rosalie Fusz Chair of Hematology, Saint Louis University Cancer Center.

From Music to Molecular Biology

Tell the readers a bit about your background before joining SLU.

I wasn’t one of these people who dreamed of a career in medicine from an early age. I was a serious musician, eventually becoming a classically trained flutist. I left college and was teaching music and playing in the San Diego Symphony. When I tried out for my first serious position at the Los Angeles Philharmonic, I thought I was a shoe in, but I wasn’t even close. After that reality check, I was largely directionless for a while until my parents insisted that I finish college.

I took some requisite science courses and a lab course in animal physiology, which I found very interesting. The professor asked me to work in his own lab; I accepted and worked with him over the summer. We published some papers together, and I became interested in pursuing molecular biology, which in the early 1970s was an emerging field. I finished college, having changed my degree from music and romance languages to cell biology, and went to graduate school at the University of California at San Diego, with my sights set on becoming a molecular biologist.

A Host of Mentors

What reshaped your career path into becoming a physician?

That decision was also a journey. I had an opportunity to work in a lab program at Washington University. After speaking with the head of the lab, I was introduced to the famous biochemist Louis Glaser, who was also the Director of the MD/PhD program. He invited me into his program, which offered a fabulous scholarship, but I turned him down because it required that I attend medical school, and I had no desire to become a doctor.

When I told my parents, my father said to call Dr. Glaser immediately and accept the offer. I did, and as I completed my MD and PhD, I discovered I really loved medicine and was also committed to doing laboratory work. I did my internship and residency at Stanford University, where I developed my interest in hematologic malignancies and became enchanted by the idea that you could use biochemistry to treat a widely metastatic disease like Hodgkin lymphoma.

One of my mentors at Stanford was former ASCO President Dr. Saul Rosenberg, who said that a fellowship at the National Cancer Institute would broaden my horizons. So I applied and was accepted to the National Cancer Institute, where I had the incredible fortune to work with notables such as Vincent DeVita, Dan Longo, Bob Young, and Marc Lippman, to name a few.

I was specializing solely in blood cancers, but then Marc Lippman’s mentorship influenced my decision to do breast cancer research as well. I left the National Cancer Institute with Dr. Lippman and others to rebuild Georgetown University’s cancer program, which eventually received its National Cancer Institute designation as a comprehensive cancer center. And then I actually went into private practice, ultimately building a community cancer center in Yakima, Washington.

After about 6 years, I got homesick for being in an academic setting and was recruited by Mike Perry to the University of Missouri, where I was Director of the Hematology Division for another 6 years. After that, I was eventually led to my position here at SLU.

An Assortment of Duties

Please describe your current work at the Center for Blood and Marrow Outpatient Transplant?

I essentially do the three legs of the academic mission: care for patients in the clinic, both with hematologic malignancies and breast cancer; teach fellows and residents; and perform clinical research as head of our clinical trials program. Then there are the administrative duties, which can be quite challenging, but I took some courses at Harvard, which have helped me in such a way that I now actually enjoy the administrative challenges.

I also have my own laboratory, which is focused on a novel approach to identifying new anticancer drugs by making alterations in lipid metabolism in cancer cells, altering the lipid composition of cell membranes to which cancer cells are particularly sensitive. This approach limits cancer cell growth, kills cancer cells, and also acts to reverse chemotherapy drug resistance.

Newer Therapies

Currently, few therapeutic strategies exist for patients with hematologic malignancies who relapse after allogeneic hematopoietic stem cell transplant. Are we making progress in this tough clinical scenario?

Yes we are. There are some newer developing therapies coming down the pike that will be helpful to these patients who are now in an unfavorable relapse position. They include immune therapies that specifically target relapsed, resistant cells, like CAR (chimeric antigen receptor) cells, for instance. Patients with acute myeloid leukemia and high-grade lymphomas are in populations that will increasingly likely benefit from being on immunotherapy clinical trials. In fact, for my patients in whom another bone marrow transplant might not be advised, I steer them to clinical trials that are looking at novel immune and monoclonal antibody therapies.

From Dismal to Hopeful

Please share a perspective of where we were and where we are today in the treatment of hematologic malignancies.

At the beginning of my career, we had a few standard chemotherapy regimens using drugs that were very toxic and relatively ineffective, except for bright spots such as Hodgkin and non-Hodgkin lymphomas and sometimes adult acute leukemias. However, over the past few decades, the dismal outlook has changed to one of more hope, in which we have actually transformed many of these once deadly cancers into curable diseases, such as acute promyelocytic leukemia. Also, the array of effective therapies we have today for chronic lymphocytic leukemia is stunning, whereas in my early years, we only had one drug, chlorambucil ­(Leukeran), for chronic lymphocytic leukemia.

The current overall picture is robust and positive. We’re in a renascence in which large clinical trials have looked at specific patient populations and have developed effective therapies for them. Moreover, we’ve seen an extraordinary process of patient population subdivision, primarily on a genetic basis, which shares properties that show us how sensitive they will be to certain chemotherapies.

Genetics With a Personal Touch

Building on our growing knowledge of genetics, what’s the next step?

Big data collection and having everybody’s genome sequenced. It will be a new paradigm for the future, the promise of truly individualized medicine. To do that, however, we’ll need to find better ways to analyze these massive data sets and apply them in a way that’s reproducible for clinicians and their patients. The sequencing of the human genome was one of the most important scientific endeavors of this century. It has opened many doors previously locked shut, and, among other things, the knowledge it has given us will ultimately make the way we currently do clinical trials obsolete. It’s really a big deal.

Are there any downsides in this new eve of genomic knowledge and rapidly deployed information?

Our advancing technology and electronic learning systems will exponentially evolve, giving us tools we can only dream of. But I’m a bit old-fashioned and a huge believer in the personal touch of oncology, creating a bond between physician and patient. I like to look past the marvelous technology and engage the patient as one person to another, taking notice of all the complex issues that go along with a diagnosis of cancer. That is the fundamental work of a doctor, and it’s very important that we never lose sight of that. But the future of oncology has never been more promising. ■

Disclosure: Dr. Freter reported no potential conflicts of interest.