Cutting-edge advances in diagnostics and treatment make this an exciting time to be practicing medicine, especially for hematologists.
“All of the things abuzz in medicine are happening in hematology,” said Aaron Gerds, MD, chair of the American Society of Hematology Committee on Communications.
Among the hottest trends in the treatment of blood diseases are chimeric antigen receptor (CAR) T-cell therapy for malignancies, which has U.S. Food and Drug Administration (FDA) approval for some indications, and clustered regularly interspaced short palindromic repeats (CRISPR) gene therapy for treating sickle cell and beta-thalassemia, which is in clinical trials.
Additionally, scientists have discovered clonal hematopoiesis of indeterminate potential (CHIP) in bone marrow cells, which has been linked to atherosclerotic cardiovascular disease.
“We are pushing the forefront of new treatments,” Gerds said.
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CAR-T therapy is a gene-based treatment that reprograms the patient’s immune system’s T cells to eliminate cancer cells. The cells are removed and reprogrammed. Then the genetically modified cells are infused back into the patient, where they will attack cancer cells and replicate.
“CAR-T is part of the wave of immunotherapy,” said Gerds, adding that CAR-T has been a huge success for certain malignancies. “We’ve seen some long-term durable remissions. It is revolutionary and has opened up a new field in hematology of cellular therapies.”
In May 2018, the FDA expanded approval for the CAR-T therapy KYMRIAH™ (tisagenlecleucel) to treat adult patients with relapsed or refractory large B-Cell lymphoma after two or more lines of systemic therapy, diffuse large B-cell lymphoma (DLBCL), and high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma.
The FDA had already approved tisagenlecleucel for children and young adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.
Although the treatment is available in clinical practice, it is expensive and reimbursement can prove challenging, Gerds explained.
“In the case where it has worked well, the tumor has been undetectable so far,” said J. Joseph Melenhorst, PhD, a researcher at the University of Pennsylvania in Philadelphia. He explained the first two patients treated with this therapy, seven years ago, have no signs of leukemia and continue to have CAR-T cells.
While CAR-T can be lifesaving for some patients, others do not respond. For instance, in clinical trials, only 26 percent of patients with advanced chronic lymphocytic leukemia had a durable response, without recurrence. Penn Medicine researchers may have found the reason some people respond and others do not.
“We figured it out, and I’m elated,” said Melenhorst, senior author of the paper in Nature Medicine, explaining the findings.
Those patients with a subset of vital, healthier T cells prior to CAR-T cell therapy had a partial or complete clinical response to the treatment, while those lacking enough of those T cells did not respond.
“We have done our discovery and validated the biomarker in a small cohort of patients,” Melenhorst said. “What we would like to do is screen patients prior, to see who will respond and see the response.”
After additional clinical trials, the Penn researchers’ discovery may lead to a hematology test that will help practicing hematologists determine which patients will benefit from CAR-T therapy, and then choose other therapies for those patients who will not respond.
Penn researchers also have found CAR-T produces high rates of durable remission in non-Hodgkin’s lymphoma and are continuing to investigate the therapy with different targeting molecules to treat different types of cancers. Other centers also are investigating CAR-T therapies.
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Researchers have identified mutations in bone marrow cells, CHIP, associated with cardiac disease and all-cause mortality. Hematology tests are currently available to determine if the patient has this mutation, Gerds said.
While treatments are not currently available, hematologists can increase monitoring of blood counts and address modifiable cardiac risk factors.
In the not-too-distant future, hematologists may have another option to offer patients with a severe form of beta-thalassemia and sickle cell disease -- gene editing, using a technology known as CRISPR.
The technique cuts a cell’s DNA and inserts a new sequence. Studies involving beta-thalassemia and sickle cell were selected, because the gene mutation is known in these two blood diseases. This year, three companies are conducting clinical trials in the United States, Europe and China.
“CRISPR is a scientific tool,” Gerds said. “Treatments spinning off CRISPR are moving toward the clinic.”
Careers in hematology
A hematology career offers opportunities to treat a variety of malignancies and non-cancerous blood diseases.
“Hematology is cool, because it has a little bit for everyone,” Gerds said. “No matter your interests in medicine, you can find it in hematology.”
Hematology is a field with tremendous research taking place, with the goal of improving patient outcomes.
“It is a research-driven field, and our understanding of the biology of these diseases is changing,” Gerds said. “When we learn something new, we try to apply that as rapidly as possible to make patients better.”
As hematology pushes forward, it remains rooted in history and the scientists who have made the discoveries that have shaped the current field.
“We are pushing the bounds of science fast, and we are incorporating new technologies and treatments at an unbelievable pace,” Gerds said. “But yet, we still have a foot in history and understand where we are coming from. That is unique to the field.”
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