ASH Clinical News ACN_4.11_Full Issue_web | Page 28

CLINICAL NEWS

The FDA granted priority-review designation to the combination of ibrutinib and rituximab for the treatment of Waldenström macroglobulinemia ( WM ). The Bruton tyrosine kinase inhibitor ibrutinib is approved as a single agent for this indication .

The supplemental new drug application was supported by data from the phase III iNNOVATE trial , which included 150 patients with relapsed / refractory and treatment-naive WM . Patients were randomized to receive either 420 mg ibrutinib or placebo ; all patients also received once-weekly 375 mg / m 2 intravenous rituximab for four consecutive weeks , followed by rituximab administered every four weeks after a three-month interval .

At 30-month follow-up , the progressionfree survival ( PFS ) rates among patients receiving the ibrutinib combination or placebo were 82 percent and 28 percent , respectively . The median PFS was not reached in the combination cohort , compared with 20.3 months in the placebo cohort ( ranges not reported ; hazard ratio [ HR ] = 0.20 ; 95 % CI 0.11-0.38 ; p < 0.0001 ).

Rates of adverse events ( AEs ) were similar in each group : All patients experienced at least one AE , and 45 and 46 patients ( 60 % and 61 %) in the combination and placebo arms , respectively , experienced a grade ≥3 AE . The most frequent grade ≥3 AEs to occur in the combination group compared with the placebo group included atrial fibrillation ( 12 % vs . 1 %; p value not reported ) and hypertension ( 13 % vs . 4 %; p value not reported ).

Sources : AbbVie press release , June 25 , 2018 ; Dimopoulos MA , Tedeschi A , Trotman J , et al . Randomized phase 3 trial of ibrutinib / rituximab vs placebo / rituximab in Waldenström ’ s macroglobulinemia . Abstract # 8003 . Presented at the 2018 American Society of Clinical Oncology Annual Meeting , June 1 , 2018 ; Chicago , IL .

The U . S . Food and Drug Administration ( FDA ) recently announced an initiative to better integrate the patient experience into clinical trials . The agency has released the first of four new guidance documents to improve the collection and use of this type of information in product development and regulatory decision-making . The documents were

developed with input from patients , patient-advocacy groups , and clinicians from more than 20 disease areas .

The first guidance , “ Patient-Focused Drug Development : Collecting Comprehensive and Representative Input ,” provides recommendations about effective approaches for obtaining patient input , standardizing data collection , and implementing these approaches into routine biologic and drug development .

“ Our work demands that we must continue to reflect on how we can make the science of drug development and review more modern and more patient-centered , so that approved products impact the metrics that real-world patients and families value most ,” FDA Commissioner Scott Gottlieb , MD , said in a press release announcing the new guidance documents .

As part of its patient-focused drug development initiative , the agency plans to release three additional guidance documents :

• Guidance 2 will discuss methods for obtaining information from patients and gathering information about issues important to such patients .

• Guidance 3 will cover the development of “ fit-for-purpose clinical outcome assessments ” to appropriately measure patient-experience data .

• Guidance 4 will discuss patientexperience data interpretation and the development of endpoints that reflect patients ’ priorities .

There is no public timeline for the release of these supplemental guidances , but the public comment period for the first draft guidance is now open .

Source : FDA news release , June 12 , 2018 .

On June 26 , 2018 , the U . S . Supreme Court voted to uphold President Donald Trump ’ s travel ban , restricting immigration from seven “ high-risk ” countries ( Syria , Iran , North Korea , Libya , Yemen , Venezuela , and Somalia ), five of which are predominantly Muslim . Several medical societies condemned the ban in its previous iterations and are now expressing concerns that this decision will endanger the U . S . health-care system .

“ We are seeing a chilling effect from the travel ban not just in the Muslim countries but a number of other countries

where people used to travel to the U . S ., not only to study and practice medicine but also other math and science careers ,” said Association of American Medical Colleges ( AAMC ) Chief Health Care Officer Janis Orlowski , MD . “ The intolerance to immigrants has raised concerns for many people who would normally come to the U . S . and study .”

Leaders from other medical organizations also warned that the policy will exacerbate the looming physician shortage in the U . S . With medical students restricted in their ability to come to the U . S . for their studies , some may choose to receive their medical education elsewhere , limiting the number of incoming healthcare providers and researchers .

The American Society of Hematology ( ASH ) has consistently opposed this policy , and previously joined with the AAMC and 33 other health-care organizations in filing an amicus brief urging the Supreme Court to oppose the order . ASH President Alexis A . Thompson , MD , released a statement on the decision . “[ The ] ruling by the Supreme Court is disappointing ,” she said . “ Every year , talented medical professionals come to the U . S . to learn , collaborate , and advance the fields of science , health , and medicine . ASH recognizes the contributions of all scientists and caregivers , regardless of national origin , and will work with lawmakers on Capitol Hill to find legislative solutions that keep our borders strong while ensuring the U . S . attracts the strongest possible biomedical research workforce from around the globe .”

Sources : ASH press release , June 27 , 2018 ; Medscape , July 2 , 2018 .

Under an emergency-use authorization , the FDA approved the use of freeze-dried plasma by the U . S . military . The authorization , requested by the U . S . Department of Defense and members of Congress , covers only the use of these plasma products for U . S . military service members during combat – not other clinical situations .

Plasma transfusions are used to treat hemorrhage and coagulopathy , which represent serious mortality threats in combative trauma situations . However , because the plasma itself typically needs to be refrigerated or frozen prior to its use , transfusions are often unavailable and impractical . The freeze-drying process eliminates the need for refrigeration or thawing , allowing plasma to be deployed

rapidly and remotely .

In a press release announcing the decision , FDA Commissioner Scott Gottlieb , MD , said that the agency is committed to expediting both the production and availability of priority medical products for the care of the U . S . military . “ This is especially true when it comes to products used to treat injuries in a potential battlefield setting ,” he noted . “ Through our collaborative program with the Department of Defense , they ’ ve made clear the importance of access to freeze-dried plasma in initial efforts to control hemorrhage from battlefield trauma .”

Sources : FDA news release , July 10 , 2018 ; Medscape , July 10 , 2018 .

The FDA approved ivosidenib , a small-molecule IDH1 inhibitor , for the treatment of adult patients with relapsed or refractory acute myeloid leukemia ( AML ) and an IDH1 mutation . This is the first IDH1 inhibitor approved for this indication , and the agent was approved simultaneously with the RealTime IDH1 Assay , a companion diagnostic designed to detect the IDH1 mutation .

The FDA based their decision on data from a single-arm study that evaluated the efficacy of ivosidenib in 174 patients with relapsed or refractory , IDH1-mutated AML . After a median follow-up of 8.3 months ( range not provided ), 32.8 percent of patients experienced complete remission ( CR ; defined as no disease evidence at follow-up and full recovery of posttreatment blood counts ) or CR with partial hematologic recovery . These responses lasted for a median of 8.2 months ( range not reported ).

In addition , of the 110 participants who were transfusion-dependent at baseline , 37 percent went at least 56 days without requiring a transfusion after ivosidenib treatment .

The most common AEs associated with ivosidenib ( ≥20 %) included fatigue , leukocytosis , arthralgia , diarrhea , dyspnea , edema , nausea , mucositis , prolonged electrocardiogram QT , rash , pyrexia , cough , and constipation . ●

Source : FDA news release , July 20 , 2018 .