Recommendations for the Moonshot Initiative
The American Society of Hematology (ASH) is the world's largest professional society serving more than 17,000 clinicians and scientists from nearly 100 countries as they work to conquer blood diseases, including cancers such as leukemia, lymphoma, and multiple myeloma. Hematologists have been pioneers in the fields of cancer immunotherapy, cellular therapy, stem cell transplantation, gene therapy, and stem cell biology with many discoveries made by hematologists translated into other fields of medicine.
With the advances gained through an increasingly sophisticated understanding of how the blood system functions, hematologists have changed the face of medicine. Breakthrough therapies for blood disorders benefit those patients who suffer from leukemia, lymphoma, and multiple myeloma. As a result, children are routinely cured of acute lymphoblastic leukemia (ALL) with chemotherapy and drugs instead of potentially dangerous transplants; more than 90 percent of patients with acute promyelocytic leukemia (APL), a fast-moving, deadly disease can now be cured with a drug derived from vitamin A; previously lethal chronic myeloid leukemia (CML) is effectively treated with well-tolerated pills; new spectacularly effective oral pills have been recently approved for patients with chronic lymphocytic leukemia (CLL); and multiple myeloma survival has been prolonged three- to four-fold by entirely new classes of drugs.
Moonshot Initiative Updates
Vice President Biden Releases Cancer Moonshot Report
Vice President Joe Biden released a report from the Cancer Moonshot Task Force on October 17, outlining the Administration's accomplishments during the last year and the initiative's goals for 2017 and beyond. The report highlights more than a dozen ongoing and future initiatives that have been launched as part of the effort, which was first announced by President Obama during his final State of the Union address in January. The report also notes the challenges posed by a lack of dedicated funding for the effort and calls on congressional leaders to approve additional funding for cancer research. Finally, the report serves as a blueprint for the next administration, offering suggestions about how the initiative could move forward.
Cancer Moonshot Blue Ribbon Panel Recommendations Align with ASH's Priorities
The Cancer Moonshot Blue Ribbon Panel recently released a report highlighting key research opportunities that should be supported so as to accelerate progress against cancer. ASH submitted recommendations to the Panel based on the ASH Agenda for Hematology Research and ASH’s Recommendations to the Moonshot Initiative (see below). The Society is pleased to see that several of its recommendations are in alignment with those of the Blue Ribbon Panel. These include: proper infrastructure for data sharing, robust clinical trials for pediatric hematologic malignancies, development of national clinical trial networks, leveraging novel therapeutic approaches such as immunotherapies for the treatment hematologic malignancies and advancing research on hematologic tumor development and progression. The Society looks forward to working with the federal agencies on these important priority areas highlighted by the Blue Ribbon Panel.
ASH strongly supports the Moonshot Initiative and would be pleased to serve as an additional resource of scientific expertise for the Administration. The following table provides specific examples of possible next steps for the Moonshot Initiative as they relate to all cancers, including hematologic malignancies. ASH recommends the inclusion of these priorities in the Initiative’s roadmap with the ultimate goal of dramatic improvements in cancer care.
Recommended Action Items
- Direct funds for research aimed at understanding the role of inherited predisposition to specific blood cancers and pre-cancerous hematologic conditions such as Fanconi Anemia, MGUS, MBL, CHIP, and MPN.
Understanding inherited predisposition to specific cancers and how a pre-cancerous condition becomes cancer will allow for early intervention and cancer prevention.
- Facilitate approval, broad utilization, and adequate reimbursement of genomic panels for diagnosis and monitoring of hematologic cancers.
Genomic testing is an important tool for diagnosis of hematologic cancers and identification of an appropriate targeted therapy for that cancer. Disease monitoring can vastly improve patient care and save lives. Patients do not have adequate access to these life-saving tests because of their prohibitive out-of-pocket costs.
- Direct funds for basic research, longitudinal genomic natural history studies, and preventive clinical trials to study hematologic models of the progression from normal blood production to blood cancers administered by NCI, NHLBI or NIDDK.
Hematologic diseases provide a unique model for studying pre-cancerous disorders and monitoring disease by non-invasive techniques that involve monitoring circulating blood cells, DNA, RNA, and other biologic material.
Recommended Action Items
- Direct appropriate funds to NCI to implement nationwide clinical trials of targeted therapies for hematologic malignancies.
- Direct funds to discover and validate genomic biomarkers of poor response to standard treatments and biomarkers of response to targeted therapies.
The NCI already has an existing network that could be leveraged for this effort, including infrastructure for supporting large multicenter clinical trials utilizing investigational drugs obtained from multiple private sector partners, consistent sample and data collection, storage, annotation, and sharing.
- Authorize a single Institutional Review Board (IRB) for federally funded cancer research (e.g., NCI IRB).
A single IRB will allow for increased patient access to clinical trials and life-saving treatments.
Recommended Action Items
- Design collaborative opportunities to improve the efficacy and reduce toxicity for patients by identifying optimal molecular targets for existing curative therapies such as allogeneic stem cell transplant, CAR T-cell therapy, and checkpoint blockade strategies. Vaccination strategies at early stages offer the opportunity to confer long-term memory immune protection against the development or recurrence of hematologic cancers.
Blood cancers such as leukemia provided a proof of principle for immunotherapy. There are exciting research opportunities to expand the utility of these novel immunologic approaches in the near term and support their implementation far beyond hematologic diseases.
Recommended Action Items
- Develop incentives to facilitate data sharing among all stakeholders to enable research and improve clinical care. Specifically, provide financial support for administrative costs of collecting, analyzing, and storing clinically and genomically profiled patient data. Provide resources for bioinformatics training for researchers and health-care providers.
- Support efforts aimed at designing proper infrastructure to host sequencing data to enable more efficient interpretation and integration of genomic information into clinical care.
- Provide additional training and education to hematologists and oncologists on using these new therapies to provide high-quality patient care and on the use of genomic assays to inform clinical care.
- ASH could be a partner in training hematologists and oncologists to manage patients undergoing treatment with these novel therapies that require different expertise from administering standard chemotherapy.
Accurate genomic data linked to clinical features is essential to advance curative strategies and delivery of personalized medicine. Collaboration is required from multiple stakeholders committed to curing cancer (e.g., philanthropy, foundations, academia, industry, medical associations, etc.). Hematologic disorders and hematologic cancers are all orphan and heterogeneous diseases. Therefore collaboration to collect clinical and genomic data on large numbers of patients with follow-up is required to ultimately deliver on the promise of precision targeted therapy.
Recommended Action Items
- Direct funds for basic and translational research to enable the discovery of new therapeutic targets in childhood leukemia.
Leukemia is the second leading cause of cancer-related death in children. New therapeutic approaches are needed to treat high-risk leukemias, to treat relapse, and to expand on the success of immunotherapy (e.g., B cell lineage ALL)
- Direct funds to support precision medicine trials in children with hematologic malignancy and/or expand the pediatric NCI MATCH trial to include this population.
Precision medicine trials are ongoing for children with solid tumors but have yet to be systematically performed for children with leukemia in part due to the complexity of treatment regimens.
- Facilitate approval, broad utilization, and adequate reimbursement of genomic panels for diagnosis and monitoring of pediatric hematologic cancers.
Genomic testing is an important tool for the diagnosis of pediatric hematologic malignancies and may aid in the identification of targeted therapies for these children (e.g., Ph-like ALL)
- Support incentives to pharmaceutical companies to test early-phase drugs in children with blood cancers. Provide support for the conduct of clinical trials testing novel therapies in children with hematologic malignancies.
Access to novel therapies is limited in pediatric cancers. There is a marked disincentive for pharmaceutical companies to develop drugs for this population.
- Provide funding to identify the determinants of toxicity and develop the next phase of precision medicine trials that de-intensify therapy for those curable with standard chemotherapy.
Toxicities of therapy for childhood leukemia are a major cause of long-term morbidity and mortality.
Recommended Action Items
- Provide the FDA with additional regulatory flexibility to speed up approvals of novel targeted agents and personalized cell therapies for hematologic malignancies. This should include a detailed assessment of current regulatory endpoints for clinical trials to ensure trial use of the best endpoints for rapid approval of effective, less toxic therapies.
- Allocate appropriate resources to the FDA to support regulatory changes and additional training required for expedited review of these therapies, and increase dialogue between hematologists, the FDA, and patient groups with a vested interest in the development of new therapies.
- ASH could be a partner in educating FDA staff; currently, ASH organizes quarterly ASH/FDA speaker series events and brings ASH member experts to the FDA to present scientific information on hematologic topics to regulators who review and approve novel therapies in hematology and oncology.
The FDA will need to expedite review and approval of novel targeted therapies by increased inter-agency collaboration.
The field of hematology has made significant contributions to human health over the last hundred years. Learn how advances in the understanding of the blood system have led to improved outcomes for patients with hematologic diseases.
Priorities for the Next Era of Hematology Research Support
- ASH Agenda for Hematology Research
ASH's research agenda serves as a roadmap for the prioritization of research support across the hematology community and includes recommendations for dedicated resources that will equip researchers to make practice-changing discoveries.
- Immunologic Treatments of Hematologic Malignancies: Moving Beyond Salvage Therapy to Curative Eradication of Minimal Residual Disease
Next-generation clinical studies will address important questions about emerging immunologic therapies but require an improved understanding of the basic biology of the immune system, including adaptive immunity, innate immunity, adjuvants, and tumor immune-surveillance.
- Precision Medicine: Tailoring Treatment and Monitoring Response to Therapy
Enhancing precision medicine efforts in hematology will require that sequencing technologies be adopted in drug discovery efforts, and in the assessment of disease predisposition, and response to therapy. In addition, appropriate infrastructure must be developed to integrate genomic and epigenomic medicine into the clinic.
- ASH Submits Recommendations to the NCI on the Cancer Moonshot Initiative
In response to a request for information from the National Cancer Institute (NCI) to advance progress against cancer through the Cancer Moonshot Initiative. ASH submitted recommendations to address research and clinical gaps that could accelerate the treatment of hematologic malignancies in precision, prevention, and early detection, expanding clinical trials, cancer immunology and prevention, enhanced data sharing, pediatric cancers, and tumor evolution and progression. ASH’s recommendations were based on the ASH Agenda for Hematology Research and ASH’s Recommendations to the Moonshot Initiative and were submitted through the NCI cancer research ideas platform. Members are encouraged to visit the NCI platform to read and/or comment on ideas submitted by ASH – the database can be filtered using keywords (e.g., ASH, hematology, blood disorders).