FDA Pipeline: Mammography Policies, Designations for Leukemias and Myelodysplastic Syndrome


This week, the U.S. Food and Drug Administration (FDA) announced policy changes to modernize mammography policies and issued a Breakthrough Therapy designation, an Orphan Drug designation, and an investigational new drug application.

FDA Advances Policy Changes to Modernize Mammography Services

The FDA announced important new steps to modernize breast cancer screening and help empower patients with more information when they are considering important decisions regarding their breast health care.

For the first time in more than 20 years of regulating mammography facilities, the agency is proposing amendments to key regulations that would help improve the quality of mammography services for millions of Americans. These actions would expand the information mammography facilities must provide to patients and health-care professionals, allowing for more informed medical decision-making. It would also modernize mammography quality standards and better position the FDA to enforce regulations that apply to the safety and quality of mammography services.

“Breast cancer is one of the most worrisome health concerns facing women. The FDA plays a unique and meaningful role in the delivery of quality mammography to help patients get accurate screening to identify breast health problems early, when they can be effectively addressed,” said FDA Commissioner Scott Gottlieb, MD. “As part of our overall commitment to protecting the health of women, we’re proposing new policies to modernize our oversight of mammography services, by capitalizing on a number of important advances in mammography, like the increased use of [three-dimensional] digital screening tools and the need for more uniform breast density reporting. We’re committed to making sure patients have access to high-quality mammography. [This] proposed rule would help ensure patients continue to benefit from advances in new tools and robust oversight of this field.”

The FDA’s proposal would amend regulations issued under the Mammography Quality Standards Act of 1992 (MQSA), which Congress passed to ensure quality mammography for early breast cancer detection. The MQSA authorizes FDA oversight over mammography facilities, including their accreditation, certification, annual inspections, and enforcement of standards to help ensure mammography facilities provide quality care.

Among the proposed amendments to improve communication and medical decision-making is the addition of breast density information to the mammography lay summary letter provided to patients and to the medical report provided to their referring health-care professionals. The FDA is proposing specific language that would explain how breast density can influence the accuracy of mammography and would recommend patients with dense breasts talk to their health-care provider about high breast density and how it relates to breast cancer risk and their individual situation.

The proposed amendments also seek to enhance information provided to health-care professionals by proposing to codify three additional categories for the assessments of mammograms, including adding an important category titled “known biopsy-proven malignancy,” which would help identify for health-care professionals those cases where cancer being mammographically evaluated for therapy are already known and identified. In addition, under the proposed regulations, both health-care professionals and patients would receive in their reports and lay summary letters more detailed identifying information about the mammography facility to aid in postexam communications.

The proposed amendments would also modernize mammography quality standards and better position FDA to enforce the MQSA regulations and take action when violations are found. Some of these proposed changes include:

  • Expressly stating that the FDA can directly notify patients and their health-care professionals, should facilities be unwilling or unable to do so, that mammography at a facility did not meet quality standards and that reevaluation or repeat of the mammogram at another certified facility may be needed
  • Requiring that only digital accessory components specifically FDA-approved or -cleared for mammography be used, or that facilities use components that otherwise meet the requirements under the rule
  • Strengthening record-keeping requirements to minimize information loss and improve access to and transfer of patient mammography records.

“Once finalized, these proposed amendments will enhance our oversight of mammography facilities, including in the key area of enforcement and patient communication,” said Jeff Shuren, MD, JD, Director of the FDA’s Center for Devices and Radiological Health. “While the majority of certified mammography facilities are dedicated to providing high levels of patient care, today’s proposed regulations would enhance the FDA’s ability to communicate directly, if needed, with patients and their health-care professionals in cases where facilities did not meet our quality standards and are not adequately communicating with patients about their facilities’ deficiencies. This is intended to help ensure important information that could affect decisions about patient care—such as the potential need for further evaluation or a repeat of a mammogram—is communicated as quickly as possible.”

The proposed rule is available online at for public comment for 90 days from publication.

Breakthrough Therapy Designation for Ivosidenib in Combination With Azacitidine in IDH1-Mutated AML

The FDA granted Breakthrough Therapy designation to ivosidenib in combination with azacitidine for the treatment of newly diagnosed acute myeloid leukemia (AML) with an IDH1 mutation in adult patients who are aged 75 years or older or who have comorbidities that preclude use of intensive induction chemotherapy. Ivosidenib is an isocitrate dehydrogenase-1 (IDH1) inhibitor.

Results from a phase I/II study of ivosidenib in combination with azacitidine were last presented at the 17th International Symposium on Acute Leukemias. In the ivosidenib arm of the phase Ib portion of the study, 23 patients received 500 mg of ivosidenib daily plus azacitidine. The median age was 76 years old, and 52% of patients were aged 75 or older. The safety profile of combination therapy remains consistent with the safety profile of ivosidenib and azacitidine alone in this patient population.

As of the August 1, 2018 data cutoff, mean neutrophil and platelet counts were maintained near or above thresholds for complete response with partial hematologic recovery while on study treatment with ivosidenib and azacitidine. Overall, 78% of patients had a response and 57% of patients had a complete response. The median duration of complete response had not been reached. The 12-month survival rate was 82%.

Orphan Drug Designation for Tinostamustine in T-Cell Prolymphocytic Leukemia

The FDA granted Orphan Drug designation to tinostamustine, a potentially first-in-class alkylating deacetylase inhibiting molecule being studied in early-phase clinical trials, for the treatment of T-cell prolymphocytic leukemia (T-PLL).

T-PLL affects approximately 2% of all patients with mature lymphocytic leukemias. It is characterized by the out-of-control growth of T-lymphocytes. The majority of patients present with hepatosplenomegaly and generalized lymphadenopathy, with skin infiltration, anemia, and thrombocytopenia often seen. T-PLL affects older adults, with a median age at diagnosis of 61 years, and it is more common in men than in women. T-PLL typically has rapid progression and does not respond well to standard multiagent chemotherapy.

Preclinical studies have shown that tinostamustine has the potential to improve access to the DNA strands within cancer cells, break them, and counteract damage repair. The preclinical data also suggest that these complementary and simultaneous modes of action have the potential to overcome resistance toward some other cancer treatments.

Investigational New Drug Application for SEL120 for AML or High-Risk Myelodysplastic Syndrome

The FDA cleared an investigational new drug application to conduct a phase I study of the selective cyclin-dependent kinase 8 (CDK8) inhibitor SEL120 in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome. The open-label, dose-escalation study is designed to evaluate safety and tolerability of SEL120 as well as to establish the recommended dose of SEL120 for subsequent clinical development.

“In preclinical studies, including studies with patient-derived xenografts, SEL120 has demonstrated strong promise using a novel and differentiated approach to treatment in AML,” commented Steffen Heeger, MD, Chief Medical Officer of Selvita. “This dose-finding study will help provide data in patients to potentially support the high selectivity of SEL120 for its target, a property that suggests potential for either stand alone or combination treatments. We expect to initiate dosing of the first patient with SEL120 in the third quarter of 2019. In addition, because of the recognized importance of CDK8 as a therapeutic target, we are optimistic about the potential for SEL120 to be evaluated in multiple indications beyond AML as the properties of this candidate in clinical settings become clear.”

The phase I study is a multicenter, dose-finding study of SEL120 in adult patients with AML or high-risk myelodysplastic syndrome who are refractory to or have relapsed after previous therapy. Patients will be enrolled in the study independent of specific cancer mutation status at baseline.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.