Clinical genomics, the molecular basis of pediatric cancer and childhood cancer survivorship are among the topics St. Jude Children’s Research Hospital researchers will discuss at the American Society of Clinical Oncology annual meeting beginning May 31 in Chicago.
The presentations will feature updates from the laboratory and the clinic in research reports, lectures, posters and poster discussions. Also, James R. Downing, M.D., St. Jude president and chief executive officer, will receive the 2019 ASCO Pediatric Oncology Award June 2.
Downing is being honored for advancing pediatric cancer care and for his scientific achievements, including his contributions to understanding the molecular landscape of childhood cancer. In a companion lecture, Downing will discuss how that progress can be used to benefit pediatric and adult cancer patients and increase cure rates around the world.
The five-day annual meeting is considered the world’s largest clinical cancer research meeting.
Date: Friday, May 31
Time: 3:57 p.m.
Title: Safety and activity of venetoclax in combination with high-dose cytarabine in children with relapsed or refractory acute myeloid leukemia
Session: Pediatric Oncology I
St. Jude researchers have demonstrated that a novel, combination-therapy strategy for relapsed or non-responsive acute myeloid leukemia (AML) is active and well tolerated in pediatric patients. The Phase I clinical trial tested a combination of the chemotherapies cytarabine and idarubicin with the novel agent venetoclax, an oral BCL-2 inhibitor. Venetoclax has previously demonstrated anti-cancer activity in adults with AML, but this is the first time the drug has been used in children. It is also the first time the drug has been combined with high-dose cytarabine and idarubicin. A phase II study of the combination is underway. “This study is an exciting first step toward the development of a novel treatment option for children with AML for whom standard therapies are frequently ineffective,” said first author Seth Karol, M.D., of the St. Jude Department of Oncology. The abstract will be presented at the conference by senior author Jeffrey Rubnitz, M.D., Ph.D., also of Oncology.
Date: Sunday, June 2
Time: 8 a.m.
Title: Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors, including central nervous system tumors.
Session: Pediatric Oncology II
Giles Robinson, M.D., of Oncology is reporting the results of a multicenter Phase I/IB clinical trial exploring the activity of the drug entrectinib. This study tested the drug against refractory or recurrent pediatric solid tumors, including central nervous system tumors. This drug targets the TrkA/B/C, ROS1 and ALK proteins, which suggested it may be useful in treating tumors that harbor aberrations in the corresponding genes NTRK1/2/3, ROS1 and ALK. The study enrolled 29 children and adolescents whose cancers did and did not have these target aberrations. The 11 patients who had target-associated fusions responded to entrectinib. Patients without the target aberrations did not respond. “For patients whose tumors have fusions in NTRK1/2/3, ROS1 or ALK, entrectinib produced a striking, rapid and durable response regardless of whether the tumor was in the brain or the body,” Robinson said. “We are excited to continue to investigate this drug in patients with these rare but often deadly pediatric solid and brain tumors that carry these fusions.”
Date: Sunday, June 2
Time: 10:12 a.m.
Title: Chronic health conditions and late mortality in survivors of acute lymphoblastic leukemia in the childhood cancer survivor study
Session: Pediatric Oncology II
Research by Childhood Cancer Survivor Study investigators has shown that risk-stratified therapy, which tailors the intensity of therapy based on clinical and biologic markers, has moved the field of pediatric leukemia survivorship in the right direction. As part of the standard treatment of pediatric acute lymphoblastic leukemia (ALL) this approach has improved survival. However, the impact on late morbidity and mortality among survivors was largely unknown.
Investigators at St. Jude recently led the largest known analysis of childhood ALL survivors to determine the impact of risk-stratified therapy approaches on late health outcomes. The researchers evaluated more than 6,000 survivors looking at late mortality, subsequent cancers, chronic health conditions and neurocognitive outcomes. Results showed that risk-stratified therapy reduced late mortality, subsequent cancers and chronic health conditions among long-term survivors of ALL. Survivors whose cancer treatment was most like contemporary standard-risk therapy had health-related mortality and subsequent cancer risks that were similar to that of the general population. “This is good news for survivors, as it suggests that previously well-established late effects, including risk for subsequent neoplasms, have been minimized for standard risk survivors of childhood ALL,” said first author Stephanie Dixon, M.D., of St. Jude Oncology.
St. Jude Cloud
The clinical value of comprehensive genomic sequencing is highlighted in St. Jude research included in the June 1 morning poster session. The poster (No. 401) will also be featured in the afternoon poster discussion, which begins at 1:15 p.m. The research reported on clinical genomic information available through St. Jude Cloud (www.stjude.cloud/), the hospital’s secure, online data-sharing and collaboration platform. The report included comprehensive whole genome, exome and transcriptome genomic sequencing data from tumor and normal tissue of more than 1,000 pediatric cancer patients along with clinical patient information. An analysis of data from the first 253 St. Jude cases found 78% of patients had clinically relevant mutations, including 11% to 16% that less comprehensive sequencing might have missed. The report marks the beginning of a new clinical genomics era at St. Jude. “We anticipate adding comprehensive clinical sequencing data from additional cases at regular intervals, totaling about 500 each year,” said first author Scott Newman, Ph.D., of St. Jude Computational Biology. “Our goal is to make this large and richly annotated dataset available sooner, rather than waiting months or years for it to accompany a publication.”
Other poster sessions will also include St. Jude research on childhood cancer survivors, including kidney function, thyroid cancer risk, heart failure screening guidelines, frailty, protein supplementations and other topics.
Alberto Pappo, M.D., director of the St. Jude Developmental Biology and Solid Tumor Program, and Tara Brinkman, Ph.D., of St. Jude Epidemiology and Cancer Control, are scheduled to lead poster discussion sections.
Pappo will discuss pediatric solid tumor research from a single institution to international collaboration June 1 at 1:45 p.m. Brinkman will discuss adolescent and young adult cancer survivors June 3 at 4:30 p.m.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20 percent to 80 percent since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food — because all a family should worry about is helping their child live. To learn more, visit stjude.org or follow St. Jude on social media at @stjuderesearch.