ASH Clinical News July 2017 V2 | Page 10

CLINICAL NEWS

The U . S . Food and Drug Administration ( FDA ) has lifted its risk evaluation and mitigation strategy ( REMS ) certification requirement for erythropoiesis-stimulating agents ( ESAs ), specifically epoetin alfa and darbepoetin alfa , for anemia related to myelosuppressive chemotherapy . The drugs are approved for anemia resulting from chronic kidney disease , chemotherapy , certain HIV treatments , and reduction in the number of blood transfusions during and after certain major surgeries .

“ The appropriate use of ESAs is supported by the Centers for Medicare and Medicaid Services ’ ( CMS ) National Coverage Determination , the American Society of Clinical Oncology , and the American Society of Hematology clinical guidelines , which are evidence-based guidelines intended to provide a basis for the standard of care in clinical oncology ,” the FDA said in a statement about this revision .

The FDA issued the REMS requirement in 2010 to mitigate the risks of adverse events ( AEs ) associated with ESAs that were identified in pivotal clinical trials , including a shorter overall survival ( OS ) and / or increased risk of progression or recurrence in patients with breast cancer , non-small cell lung cancer , head and neck cancer , lymphoid cancer , and cervical cancer . Under this program , providers and hospitals were required to become certified in the ESA REMS , provide counseling to each patient , and have each patient complete a Patient and Healthcare Provider Acknowledgment Form prior to treatment with the agents .

After conducting a REMS assessment and surveying prescribers , the FDA determined that the ESA REMS was no longer necessary to “ ensure the benefits [ of ESAs ] outweigh the risks .” In data from 2006 to 2014 , Amgen ( the manufacturer of darbepoetin alfa ) demonstrated a decrease in the number of patients receiving chemotherapy who warranted ESAs , suggesting a lower overall risk . In addition , trend analysis showed that the introduction of the REMS had little impact on ESA usage .

“ The prescribing information continues to note an increased risk of tumor progression or recurrence , as well as death , myocardial infarction , stroke , venous thromboembolism , and thrombosis of vascular access ,” the FDA cautioned . The labels for both treatments note that they should only be used with myelosuppressive chemotherapy when at least 2 months of treatment with chemotherapy are planned . The agents also should not

be used in combination with hormonal agents , biologic products , or radiotherapy , unless the patient is also receiving myelosuppressive chemotherapy .

Source : U . S . Food and Drug Administration news release , April 13 , 2017 .

The FDA granted breakthrough-therapy designation for CTL019 , a chimeric antigen receptor T-cell therapy , for adult patients with relapsed / refractory diffuse large B-cell lymphoma ( DLBCL ) for whom ≥2 prior therapies have failed them . The designation was based on results from the multicenter , phase II JULIET study , for which results have not yet been published .

CTL019 also received breakthroughtherapy designation for the treatment of pediatric and young adult patients with relapsed / refractory B-cell acute lymphocytic leukemia ( ALL ). The FDA previously granted a priority-review designation for CTL019 in this patient population based on findings from the global phase II ELIANA study , a multicenter trial conducted in the United States , and a single-institution trial .

The ELIANA trial demonstrated a rate of complete remission ( CR ) or CR with incomplete blood count recovery ( CRi ) of 82 percent with CTL019 , with all patients achieving a CR / CRi becoming minimal residual disease-negative ( 95 % CI 69-91 ; p < 0.0001 ). CTL019 treatment also led to a 6-month OS rate of 89 percent ( 95 % CI 76-95 ) and a disease-free survival rate of 60 percent . The ELIANA study enrolled patients from 25 centers in the United States , Europe , Asia , and Australia . At the time of the assessment , 50 patients ( median age = 12 years ; range = 3-23 years ) received lymphodepleting chemotherapy ( including fludarabine 30 mg / m 2 daily for 4 doses and cyclophosphamide 500 mg / m 2 daily for 2 doses ) prior to CTL019 infusion ( 2.0-5.0x10 6 kg for patients ≤50 kg and 1.0- 2.5x10 8 kg for those > 50 kg ). A majority of patients ( 56 %) had undergone prior hematopoietic cell transplantation , and the median number of prior lines of therapy was three ( range = 1-8 therapies ).

Eighteen patients discontinued treatment because of death ( n = 6 ), relapse ( n = 5 ), beginning new therapy while in CR ( n = 5 ), or patient or guardian decision ( n = 2 ). Two deaths were reported within 30 days of treatment ( 1 from ALL and 1 from cerebral hemorrhage ). Seventy-one percent of patients experienced an AE within the first 8 weeks of treatment , of which 68 percent were deemed treatment related .

Forty-eight percent of patients experienced grade 3 or 4 cytokine release syndrome ( CRS ), but researchers noted that there were no deaths related to CRS . Fifteen percent of patients experienced grade 3 neurologic and psychiatric AEs ( including confusion , delirium , encephalopathy , agitation , and seizure ), but no cerebral edema was reported .

Sources : Novartis press release , March 29 , 2017 ; Novartis press release , April 18 , 2017 .

In March , the National Library of Medicine ( NLM ) implemented a series of changes to how conflict-of-interest ( COI ) information is displayed in PubMedindexed abstracts . COI statements will now be displayed on the front page of an article ’ s abstract to alert readers to any possible industry influence over studies .

The changes are a response to concerns about transparency , which more than 60 scientists raised in a 2016 letter to National Institutes of Health Director Francis Collins , MD , PhD , and NLM Acting Deputy Director Betsy Humphreys , MLS . COI statements are often buried at the end of articles , making it difficult for readers to discern whether studies have potentially been influenced by industry sponsors when they are searching literature databases like PubMed , which includes only study abstracts .

“ Adding disclosures about researchers ’ financial relationships with drug , food , chemical , and other industries makes PubMed search results even more useful than they already are ,” Michael F . Jacobson , PhD , president of the Center for Science in the Public Interest , which cosigned the 2016 letter to Dr . Collins and Ms . Humphreys , said in a statement . “ We thank the NLM for adding this feature and hope journalists who rely on PubMed make consistent use of it when reporting on studies related to nutrition and health .”

Sources : Vox , April 19 , 2017 ; Collins M . PubMed updates March 2017 . NLM Tech Bull . 2017 ; 415 : e2 .

A new rule from CMS proposes increasing transparency of the inspection process of medical facilities by requiring that private health-care accreditors ( the largest of which is The Joint Commission ),

which usually conduct inspections , publicly report outcomes of inspections and hospitals ’ plans to resolve reported problems . The reports would not specifically name staff members , but would include details about medication errors , operations on the wrong patient or body part , and patient abuse .

These reports have long been confidential , but CMS proposed the new rule to address concerns about private accreditors missing major problems at health-care facilities . Though the U . S . Department of Health and Human Services must approve accreditors , they rarely take action against the organizations .

Each year , CMS reviews a sample of hospitals and other health-care facilities accredited by private organizations to validate their findings . In the 2014 inspection of 103 acute-care hospitals , state inspectors found 41 serious deficiencies , 39 of which were missed by private inspectors . This “ raises serious concerns regarding the [ accrediting organizations ’] ability to appropriately identify and cite health and safety deficiencies ,” CMS said in a statement of the draft regulations . “ We believe it is important to continue to lead the effort to make information regarding a healthcare facility ’ s compliance with health and safety requirements .”

The proposed rule would also change regulations “ relating to transparency of accrediting organization survey reports and plans of correction of providers and suppliers ; electronic signature and electronic submission of the Certification and Settlement Summary page of the Medicare cost reports ; and clarification of provider disposal of assets .”

In response to this draft regulation , the American Hospital Association ( AHA ) voiced its support for providing the public “ useful information ” but noted that the reports may not be interpreted easily by the general public . “ It ’ s important that the information shared with consumers has a clear purpose , is transparent , and is readily understood by folks from all walks of life , not just those with deep expertise in health care ,” said Nancy Foster , vice president for quality and patient safety at the AHA , in a statement , recommending the publication of a shorter summary document that explains key findings and significance .

The new requirements would apply to specific Medicare providers , including acute-care hospitals , Prospective Payment System-exempt cancer hospitals , long-term care hospitals , and inpatient psychiatric facilities . ●

Sources : NPR and ProPublica report , April 18 , 2017 ; Federal Registrar Document 2017-07800 , April 28 , 2017 .