The most common pediatric cancer is acute lymphoblastic leukemia (ALL), a diagnosis that 50 years ago was devastating with a bleak five-year relative survival rate. Through the course of my career, I have provided medical care for children with ALL, directed a laboratory at the National Cancer Institute studying the basis for the malignant transformation of cells leading to ALL, and worked to develop drugs relevant to the treatment of patients with ALL at Amgen, all building to my current role as the Senior Vice President of Translational Medicine at Adaptive.
As a pediatric oncologist it has been highly rewarding to bear witness to what has become a success story in cancer treatment. Today 85-90% or more of children diagnosed with ALL can be cured. However, this progress has not been without some cost. Treatment regimens lasting 2-3 years have been aggressive, and for some survivors there have been long term sequelae, or complications. For children with another 80 years to live, we must strive to develop effective therapies with the least associated toxicity possible.
September is both Childhood Cancer Awareness Month and Blood Cancer Awareness Month. For me, while it’s a special time to celebrate how far we’ve come, I keep my focus on how much further we have to go. I am proud to be able to continue to pursue my commitment to childhood cancer patients through my work at Adaptive.
The cure of childhood ALL has been achieved in large part by regimens initially utilizing a mix of radiation and combination chemotherapy, and, more recently, the introduction of more targeted therapies to kill leukemia cells and put the disease into remission.
To enable us to reconsider aggressive non-specific therapies, it is critical to employ risk stratification strategies to allow for tailoring a therapeutic approach for each specific patient, augmenting treatment in some patients or reducing treatment in others. Standardized, highly sensitive, and accurate assays that measure residual disease (MRD) such as flow cytometry and next generation sequencing (NGS) (such as clonoSEQ®) provide critical insights into tumor burden, tumor response to therapy, and tumor growth kinetics over time, if serial measurements are employed.
These assessments are now becoming routinely incorporated into the care of children with leukemia. For example, I recently spoke with Kasey Leger, MD, an attending physician at Seattle Children’s Hospital who uses clonoSEQ to monitor high risk patients prior to and following transplant or CAR T cell therapy. For her, clonoSEQ has been a valuable tool for measuring treatment responsiveness and identifying lower levels of residual or recurrent leukemia than was previously possible. Importantly, she notes, “Families really appreciate the insight it offers. Once a child’s family knows about clonoSEQ and understands the weight we’re starting to put in it, they are definitely interested in those results.” Dr. Leger is now also the site leader for an ongoing study being run by the Children’s Oncology Group researching how clonoSEQ can guide upfront treatment for patients with standard risk ALL. The use of advanced MRD methods for assessment of standard risk patients offers a more personalized treatment plan and may lead to improved outcomes with less toxicity.
This September, for those working to improve the lives of children with blood cancers, we recognize the progress that’s been made, but the battle is not over. Research and advocacy for disease monitoring will continue to strengthen and personalize therapeutic approaches to improve efficacy and reduce toxicity for childhood ALL patients, and hopefully improve long-term quality of life.
clonoSEQ® is available as an FDA-cleared in vitro diagnostic (IVD) test service provided by Adaptive Biotechnologies to detect minimal residual disease (MRD) in bone marrow from patients with multiple myeloma or B-cell acute lymphoblastic leukemia (B-ALL) and blood or bone marrow from patients with chronic lymphocytic leukemia (CLL). clonoSEQ is also available for use in other lymphoid cancers and specimen types as a CLIA-validated laboratory developed test (LDT). For important information about the FDA-cleared uses of clonoSEQ including test limitations, please visit clonoSEQ.com/technical-summary.