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months or longer and do not have another identifiable non-hematologic cause of the disease .
Mepolizumab is the first therapy in nearly 14 years to be approved for patients with this heterogenous group of rare disorders , which is associated with persistent eosinophilia and organ damage . Symptoms of HES can include congestive heart failure , deep vein thrombosis , and anemia . The treatment received orphan drug designation .
This approval is based on results from a phase III trial that compared the proportion of patients with at least one HES flare over a 32-week period in those treated with mepolizumab versus those receiving placebo . HES flares were defined as worsening symptoms or increasing eosinophils on at least two occasions . Fewer patients receiving mepolizumab experienced flares than patients in the placebo group ( 28 % vs . 56 %). The average time to first flare also was later in the mepolizumab group than the placebo group .
AEs associated with mepolizumab include upper respiratory tract infection and extremity pain . The FDA advises clinicians to consider shingles vaccination for patients receiving mepolizumab , if medically appropriate .
Sources : FDA press release , September 25 , 2020 ; ClinicalTrials . gov , NCT00086658 .

Idecabtagene Vicleucel Granted Priority Review for Myeloma

The FDA has granted priority review to the biologics license application of idecabtagene vicleucel ( ide-cel ), for the treatment of adult patients with MM who have received at least three prior therapies , including an immunomodulatory agent , a proteasome inhibitor , and an anti-CD38 antibody .
Ide-cel , formerly known as bb2121 , is an investigational B-cell maturation antigen ( BCMA )- directed chimeric antigen receptor ( CAR ) T-cell therapy .
The FDA ’ s acceptance for regulatory review is based on results from the phase II KarMMa study , which were presented as part of EHA25 Virtual , the 25th Annual Congress of the European Hematology Association .
In this open-label , single-arm study of 128 patients with triple-class – exposed MM , ide-cel was administered at target doses of 150 to 450 × 10 6 cells / kg . Ninety-three patients ( 73 %) responded to treatment with ide-cel , including 26 % of patients who became negative for measurable residual disease . Median progression-free survival was 8.8 months , and the median duration of response was 10.7 months among all responders . The most common any-grade AEs included cytopenias ( 97 %) and cytokine release syndrome ( 84 %). Twenty-three patients ( 18 %) developed neurotoxicity .
Ide-cel was granted breakthrough therapy designation by the FDA and has been granted PRIME ( PRIority MEdicines ) designation by the E . U .’ s European Medicines Agency .
Source : Bristol Myers Squibb press release , September 22 , 2020 .

Crizotinib Receives Priority Review for Pediatric ALCL

The FDA has granted priority review to a supplemental new drug application for crizotinib to treat pediatric patients with relapsed / refractory systemic anaplastic large cell lymphoma ( ALCL ) that is ALK-positive .
“ Despite high survival rates for children with ALK-positive ALCL , many will relapse , requiring novel treatment approaches ,” said Chris Boshoff , MD , PhD , Chief Development Officer of Oncology at Pfizer . If approved , crizotinib would be the first biomarker-driven therapy for this indication .
In May 2018 , crizotinib received breakthrough therapy designation from the FDA for systemic ALK-positive ALCL in pediatric patients . The E . U .’ s European Medicines Agency also agreed to a pediatric investigational plan for crizotinib for this indication .
The FDA ’ s decision is based on results from the phase I / II ADVL0912 study and phase I A8081013 study . ADVL0912 tested the maximum safe dose of crizotinib in pediatric patients with relapsed or refractory solid tumors and ALCL . A8081013 evaluated crizotinib in adult and pediatric patients with ALK-positive cancers other than nonsmall cell lung cancer , including in patients with relapsed / refractory ALCL .
Sources : Pfizer press release , September 23 , 2020 ; ClinicalTrials . gov , NCT00939770 ; ClinicalTrials . gov , NCT01121588 .

NASEM Releases Sickle Cell Disease Report

The National Academies of Sciences , Engineering , and Medicine ( NASEM ) recently released a report titled “ Addressing Sickle Cell Disease : A Strategic Plan and Blueprint for Action ,” examining the prevalence of and genetic and societal factors associated with sickle cell disease ( SCD ) and sickle cell trait . The report , which was commissioned by the U . S . Department of Health and Human Services ( HHS ), also evaluated the current state of care for people with SCD by looking at clinical practice guidelines , best practices , and programs available for patients .
The American Society of Hematology ( ASH ) commends NASEM on its report , with 2020 ASH President Stephanie Lee , MD , MPH , issuing the following statement : “ Conquering SCD is a clear priority for ASH and the ASH Research Collaborative , and this NASEM strategic plan and blueprint for addressing SCD in the United States is an important milestone toward improvement . ASH applauds HHS and HHS ’ s Office of Minority Health for the foresight to commission this report to help set a path forward toward better care for the approximately 100,000 Americans with the disease and their loved ones .”
Specifically , the Society noted that the report prioritizes the need to further identify and address barriers to access to quality care , especially for adults with SCD , who often face challenges accessing appropriate and coordinated care when they have to switch from pediatric to adult providers . “ Individuals living with SCD not only are burdened with the pain and disability from a chronic disease , but they also have few treatment options and most lack access to appropriate care due to a fragmented health care system and insufficient SCD knowledge and experience in the clinician workforce ,” Dr . Lee said . “ The status quo is unacceptable .”
ASH also applauded the committee for prioritizing the need for expanded data collection .
“ ASH appreciates that NASEM engaged multiple stakeholders , including many ASH members working in SCD , to craft a blueprint for finally improving the health of this population ,” Dr . Lee continued . “ Now we must work together to enact these recommendations .”
Source : American Society of Hematology press release , September 10 , 2020 .

“ Off-the-Shelf ” CAR T-Cell Therapy for Myeloma Receives Fast Track Designation

The FDA has granted fast track designation to PBCAR269A , an allogeneic CAR T-cell therapy for the treatment of patients with relapsed or refractory MM whose disease failed to respond to two prior therapies , including an immunomodulatory agent and a proteasome inhibitor .
Unlike currently approved CAR T-cell therapies , PBCAR269A is a donor-derived therapy that uses T cells from healthy donors , which allows for the production of an “ off-the-shelf ” treatment . The therapy is being evaluated in an open-label , nonrandomized phase I / IIa trial at starting doses of 6 × 10 5 cells / kg , escalating to 6 × 10 6 cells / kg in subsequent cohorts .
PBCAR269A also received orphan drug designation . The treatment is being investigated in a phase I / IIa trial ( NCT04171843 ) enrolling 48 participants across five U . S . institutions .
Sources : Precision BioSciences press release , September 21 , 2020 ; ClinicalTrials . gov , NCT04171843 .

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42 ASH Clinical News November 2020