Blood cancer research has shown improvements in early detection and treatment advancements, which are associated with increased survival. However, more research is needed to improve the overall survival rates for the most difficult-to-treat blood cancers and minimize long-term complications of treatment.
“Approximately every 3 minutes one person in the United States (US) is diagnosed with a blood cancer. An estimated combined total of 178,520 people in the US are expected to be diagnosed with leukemia, lymphoma or myeloma in 2020. New cases of leukemia, lymphoma and myeloma are expected to account for 9.9 percent of the estimated 1,806,590 new cancer cases diagnosed in the US in 2020.”
This article was written in collaboration with the following experts:
Joanna Perkins, MD, MS, Senior Medical Director, Medical Affairs, Hematology-Oncology
Missy Hansen, MSN, APRN, CNP-Pediatrics, Pediatric Strategy Liaison, Scientific Affairs
Martine Dehlinger-Kremer, PhD, Vice President of Scientific Affairs, Pediatric Subject Matter Expert
This month is the Leukemia and Lymphoma Society’s Blood Cancer Awareness Month. September 4 is World Leukemia Awareness Day, and September 15 is World Lymphoma Awareness Day. To honor these therapeutic awareness initiatives, we spoke with a few of our leukemia and lymphoma experts about their experience working with blood cancers and how these diseases affect adult and child populations differently.
Tell us about your experience and what you’ve learned from working with leukemia, lymphoma, and other blood cancers.
JP: I am a pediatric hematologist-oncologist. Prior to joining PRA, I spent years in clinical practice at a large children's hospital system. The majority of my clinical and research work has focused on pediatric leukemias and lymphomas. Part of the reason why Missy and I both have a lot of experience working with pediatric leukemias, particularly pediatric acute lymphoblastic leukemia (ALL), is that it's the most common childhood cancer. Pediatric leukemias account for approximately 25% of new cancer diagnoses in children, the majority of which is ALL. Fortunately, ALL is also one of the most curable diseases.
Since coming to PRA, I’ve been involved primarily with leukemia trials, both in children and adults. Historically, CROs were not routinely involved with most clinical trials in pediatric cancers. The majority of childhood cancer treatment has been administered according to clinical trials conducted by Children's Oncology Group and other large pediatric cancer consortia worldwide. With the implementation of the RACE (Research to Accelerate Cures and Equity) for Children Act, there will be more pharmaceutical-sponsored clinical trials in childhood cancers, where CROs like PRA will be more directly involved.
MH: One thing that always comes to mind for me is that historically, pediatric cancer had only about a 20% overall survival rate. Over the last several decades that has increased to an 80% overall survival rate. I think that is so phenomenal, and now that we have RACE Act, we can work on making that overall survival rate even better.
As we're gearing up to use more precision medicine (or molecularly targeted treatments) in the field of pediatric cancer treatment, one of our first goals should be to target those diseases with a still poor overall survival rate—including some subsets of leukemia and lymphoma.
In terms of overall cure rate, targeted therapy may give those with still poor outcomes a better chance for survival. We also know that approximately 80% of all children treated for cancer have lifelong effects and risks from their initial treatment, so addressing this issue with targeted therapies that continue to cure them of their disease but offer less risk of late effects is paramount as well.
JP: For certain types of diseases like low-risk pediatric ALL, the cure rate is even higher, over 90%. One of the most important reasons behind that cure rate is that rapid progress can’t happen by developing individual treatment plans.
Early pediatric cancer researchers recognized this, due to the rare incidence of these childhood cancers. The researchers formed networks, for example Children's Oncology Group, which is a consortium of major cancer centers that treat children in North America and other parts of the world.
By treating children according to standardized protocols, they were able to streamline efforts to better understand the causes of cancer and constantly improve upon treatments. This is much more efficient than individual cancer centers working in silos. Sharing data and research advancements through consortia led to an incredible improvement in overall survival for children with cancer.
The causal agent for blood cancers such as lymphoma and leukemia are not well known. Can you tell us more about that and provide developments in that area in the recent past?
JP: For the most part, we don't understand what causes cancer. There have been large epidemiological studies looking at underlying etiologies of cancer, but with otherwise very few exceptions, there really isn't an answer as to what causes most cancers.
Cancer encompasses many diseases, all of which behave, develop, and receive treatment differently. The term “cancer” describes an uncontrolled growth of abnormal cells in any part of the body. We believe we all may have some predisposition to the development of diseases like cancer—likely a combination of some environmental factors and underlying genetic factors.
MH: I think it’s also important to prioritize reducing long-term effects of cancer therapies. For example, years ago it was standard for many children with leukemia to get cranial and spinal radiation. We know now that this puts them at risk for learning difficulties and secondary cancers, especially brain tumors. So, cranio-spinal radiation therapy is now only administered to the highest risk patients.
JP: In addition to radiation exposure, there are certain chemotherapy drugs that are known to cause secondary leukemias. As a result of their cancer treatment, a patient is at a higher risk for the development of a second cancer.
Based on what we’ve learned about risks for second cancers, we’ve modified our treatment plans over time to maintain or improve overall survival while reducing late effects. For example, we know that girls and young women who receive chest radiation for Hodgkin lymphoma have a high risk for secondary breast cancer. As a result, we’ve tried to minimize the amount of radiation that's administered. As with leukemia patients, radiation is now reserved for only the highest risk patients.
MH: Sometimes the difficult conversations, or the ones that take the longest, are when you're trying to explain the risks associated with a patient’s treatment. When you talk to a patient and their family who want to know what caused his/her cancer, you can’t give them a definitive answer because we simply don’t have one. Reviewing the likelihood of risks and the potential short- and long-term effects of the recommended treatment can be especially difficult.
How do blood cancers affect adult and child populations differently, and how will the RACE Act address these differences?
JP: The incidence of specific types of leukemia and lymphoma are different in children versus adults. For example, the majority of pediatric leukemia cases are acute lymphoblastic leukemia (ALL), with a smaller percentage being acute myelogenous leukemia (AML), and rarely chronic myelogenous leukemia (CML). We see the reverse pattern in adults. The majority of leukemia cases in adults are AML, whereas ALL makes up a much smaller percentage. Adults also have a higher incidence of CML, as well as chronic lymphocytic leukemia (CLL), a disease rarely seen in pediatrics. Adults tend to have more aggressive types of leukemia.
Another difference is that overall, children tend to have higher survival rates. They generally endure the toxicities of treatment better than someone who's older or has other co-morbidities.
MDK: In high-income countries, children are diagnosed at an early stage. But in low-income countries, children are often diagnosed at a later stage, so the survival rate is frequently lower. Even with diagnoses like solid tumors or lymphomas, children in low-income countries tend to be diagnosed at a much later stage when the disease has metastasized and poses a potentially higher risk. This of course affects outcomes.
MH: In talking about the consortia and how they treat many children, for example with Children's Oncology Group clinical trials, we know that those kids and adolescents often fare better if treated on a trial. A trial is often a first-line treatment option for many newly diagnosed with a pediatric cancer, which is different when compared to other therapeutic areas.
JP: There is research to show that young adults with certain kinds of leukemia like ALL have superior outcomes if they’re treated at pediatric cancer centers. At these centers, young adults are more likely to be enrolled in clinical trials. That's not to say that clinical trials aren't important in adult oncology as well, but it’s common practice that clinical trials are offered at initial diagnosis for most pediatric cancer patients. This contributes to learning and advancing our knowledge much more quickly than when patients are not a part of a clinical trial.
MDK: The RACE for Children Act will have a significant impact on the way those oncology clinical trials will be conducted. It will also have effect on the number of oncology pediatric clinical trials.
JP: Previously, pharmaceutical companies were not obligated to study a new cancer drug in children if the cancer of interest did not occur in children. Now, they’re required to follow clinical trial development according to molecular targets of the cancer as opposed to the specific disease. For example, we know that certain cancers share molecular targets even if they aren't the same disease. If the molecular target of a drug that's being developed in adults is also present in a pediatric cancer, they would need to include children in those trials, regardless of the diagnosis.
MH: The goal of the RACE for Children Act, according to the FDA, is to get more pediatric cancer drugs in the pipeline. Adults with cancer historically have been offered precision medicine therapies for much longer. It’s time to uniformly apply this to children.
Can any of you speak to how precision medicine has changed treatment paradigms, such as with Chimeric Antigen Receptor T-Cell (CAR-T) therapy? What’s the future of this precision medicine and how will it change these treatments?
JP: The historical approach to cancer treatment has involved using primarily cytotoxic (killing cells) chemotherapy. This type of treatment kills the cancer cells, but also injures many healthy “innocent bystander” cells in the body as well. This may result in numerous side effects and risk of long-term complications. With precision medicine, rather than exposing the whole body to drugs that kill all types of cells, we look at the cancer’s specific molecular makeup—what specific targets the cancer might have. Then, we develop drugs that attack just those targets. The hope then becomes efficiently curing the cancer with less side effects to the healthy cells of the body, as well as a lower risk for long-term complications.
CAR-T cell therapy involves harvesting a person's own immune cells and programming them to target the patient’s leukemia cells. This process is a much more targeted treatment against that patient's own specific leukemia than conventional cytotoxic chemotherapy.
MH: Leukemia is really just an umbrella term representing many different diseases. When targets are identified for a patient’s leukemia, they may be treated based on that molecular abnormality. Two patients may have the same type of leukemia, but they get different treatments because they do or don't have a specific target related to their disease. That contributes to overall prognosis and the short and long-term effects years later.
Addressing the clinical needs of children based only on what works in adults is no longer acceptable. Our Center for Pediatric Clinical Development has unparalleled pediatric expertise built on a foundation of analytics, partnerships, and experience. We help our clients save time and resources by determining the feasibility and effectiveness of pediatric studies at every phase of a program. Our global experience allows us to develop and execute country-specific, customized recruitment and retention initiatives to help study teams meet or exceed goals.
CAR T-Cell Therapies – The Holy Grail of Therapeutic Innovation in Hemato-Oncology and its Challenges from a CRO Perspective
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