ASH Clinical News ACN_4.6_Full_Issue_web | Page 28

Adult patients undergoing hematopoietic cell transplantation ( HCT ) can safely delay platelet transfusion until the first sign of bleeding , according to an update to clinical practice guidelines from the American Society of Clinical Oncology ( ASCO ). According to guideline authors , the recommendation is “ the most substantial change ” to previous guidelines published in 2001 , which recommended prophylactic platelet transfusions for this patient population .

“ The [ 2001 ] guideline recognized the important role of platelet transfusion in the prevention and treatment of bleeding in patients with treatment-related thrombocytopenia , but also sought to avoid the overuse of platelet transfusions by identifying patients who are most likely to benefit ,” the authors wrote of their recommendations , which were published in The Journal of Clinical Oncology . “ The expense of platelet transfusions , coupled with potential [ adverse events ( AEs )], such as febrile and allergic reactions , transfusion-related acute lung injury , and bacterial contamination , point to the importance of evidence-based transfusion practice .” Prophylactic platelet transfusion at defined platelet count thresholds is still recommended for children undergoing autologous HCT and patients undergoing allogeneic HCT ( alloHCT ).

To create the new guidelines , ASCO convened an expert panel to review 11 clinical questions related to the preparation , prophylactic use , and appropriate thresholds for the use of platelet transfusions in patients with cancer . They reviewed medical literature published from September 1 , 2014 , through October 26 , 2016 , and built on two 2015 systematic reviews that were conducted by AABB and the International Collaboration for Transfusion Medicine Guidelines .

This guideline update confirms the validity of several earlier recommendations but modifies others in the areas of :

• Prevention of Rh alloimmunization : This can be achieved through the exclusive use of platelet products collected from RhD-negative donors or via anti-D immunoprophylaxis ( evidence quality : intermediate ; strength of recommendation : moderate )

• Leukoreduction : It is appropriate to provide leuko-reduced blood products to patients with acute myeloid leukemia

( AML ) receiving induction therapy to reduce the risk of alloantibody-mediated refractoriness to platelet transfusion ( evidence quality : high ; strength of recommendation : strong )

• Platelet transfusion threshold in patients with solid tumors : The panel recommends a threshold of < 10 × 10 9 / L for prophylactic platelet transfusion to minimize the risk of bleeding from chemotherapyinduced thrombocytopenia in patients with solid tumors ( evidence quality : low ; strength of recommendation : moderate )

• Monitoring for refractoriness to platelet transfusion : Platelet counts performed 10-60 minutes after transfusion should be obtained after all transfusions when refractoriness is suspected , although there are no empirical data to suggest that monitoring and acting on the post – platelettransfusion count decreases the incidence of hemorrhagic events ( evidence quality : insufficient ; strength of recommendation : moderate )

Source : Schiffer CA , Bohlke K , Delaney M , et al . Platelet transfusion for patients with cancer : American Society of Clinical Oncology clinical practice guideline update . J Clin Oncol . 2018 ; 36:283-99 .

A report published in Proceedings of the National Academy of Sciences found that funding from the National Institutes of Health ( NIH ) contributed to published research associated with every drug approved by the U . S . Food and Drug Administration ( FDA ) between 2010 and 2016 . This amounts to 210 drug approvals , 84 of which were first-in-class agents .

Researchers at Bentley University conducted a literature review for mentions of each new molecular entity , as well as studies of their molecular targets . They then cross-checked to determine which of those studies had received any NIH funding . More than $ 100 billion in NIH funding went supported research that contributed – directly or indirectly – to the 210 drugs approved in the six-year study period . The R01 grant was the most common source of this funding , and 90 percent of the publications were related to the biological targets of the drugs , rather than the drugs themselves .

“ This work underscores the breadth and significance of public investment in

the development of new therapeutics ,” the authors concluded , “ and the risk that reduced research funding would slow the pipeline for treating morbid disease .”

Source : STAT News , February 12 , 2018 ; Cleary EG , Beierlein JM , Khanuja NS , et al . Contribution of NIH funding to new drug approvals 2010 – 2016 . Proc Nat Acad Sci . 2018 February 6 . [ Epub ahead of print ] February 14 , 2018 .

A new report from the U . S . Centers for Medicare and Medicaid Services ( CMS ) projects that health-care spending will increase 5.3 percent in 2018 – up nearly one percentage point from the 2017 projections . The researchers cite three primary drivers for this higher projection : an aging population that will expand the number of eligible Medicare beneficiaries , hikes in the prices for medical goods and services , and more disposable personal income .

CMS projects that health-care spending will rise , on average , 5.5 percent annually between 2017 and 2026 ; by 2026 , health spending will comprise 19.7 percent of the U . S . economy , reaching $ 5.7 trillion . Spending on prescription drugs is expected to see the fastest annual growth over the next decade , rising an average of 6.3 percent per year because of higher drug prices and increased use of specialty drugs .

The report also predicts that a slightly higher portion of the population will be uninsured in 2026 .

Source : Reuters , February 14 , 2018 .

The U . S . Food and Drug Administration ( FDA ) cleared the use of the Trevo clot retrieval device to treat certain stroke patients up to 24 hours after symptom onset – an increase from the original clearance of up to six hours after symptom onset .

“ Time is critical following the onset of stroke symptoms ,” said Carlos Peña , PhD , director of the Division of Neurological and Physical Medicine Devices at the FDA ’ s Center for Devices and Radiological Health . “ Expanding the treatment window from six to 24 hours will significantly increase the number of stroke patients who

may benefit from treatment .”

The Trevo device is approved for use as an initial therapy for ischemic strokes to help reduce paralysis , speech difficulties , and other stroke-related disabilities . In 2012 , the FDA initially approved the device to remove blood clots and restore blood flow in stroke patients who could not receive tissue plasminogen activator ( t-PA ) therapy or for those who did not respond to this treatment . In 2016 , the FDA expanded the window of treatment to within six hours of symptom onset when used with t-PA .

The decision to further expand the treatment window was based on clinical trial data comparing 107 patients treated with the Trevo device and medical management versus 99 patients treated only with medical management . Approximately 48 percent of patients treated with the Trevo device were functionally independent ( ranging from no symptoms to slight disability ) three months post-stroke , compared with 13 percent of patients who were treated with medical management alone .

AEs associated with the device include a failure to retrieve the blood clot , embolization to new territories in the brain , arterial dissections and vascular perforations , and access site complications at the femoral artery entry point .

Source : U . S . Food and Drug Administration press release , February 15 , 2018 .

The FDA granted priority review to ivosidenib for the treatment of relapsed / refractory IDH1-mutated AML . The decision was based on results from an ongoing , single-arm , phase I trial that included 258 patients ( 78 in the dose-escalation phase and 180 in the dose-expansion phase ). As of May 12 , 2017 ( data cutoff ), 24 percent of patients ( n = 62 ) were continuing treatment , and the median duration of ivosidenib exposure was 3.5 months ( range = 0.1-33.5 months ). Twenty-two patients ( 8.5 %) discontinued treatment and went on to receive alloHCT .

The most common any-grade AEs ( occurring in ≥20 % of patients ) were diarrhea ( 33 %), leukocytosis ( 30 %), nausea ( 30 %), fatigue ( 29 %), and febrile neutropenia ( 25 %). Twenty-nine participants ( 11.2 %) reported differentiation syndrome ( DS ), 14 ( 5.4 %) of which were grade ≥3 .