ASH Clinical News June 2016 | Page 17

CLINICAL NEWS

The International Cancer Genome Consortium ( ICGC ) announced plans to launch the ICGC for Medicine ( ICGCmed ), a new phase of the consortium that will link genomics to clinical information and health . The collaborative project will build upon the vast database of genomic discoveries of the ICGC , which , since its launch in 2007 , has been mapping 25,000 different cancer genomes in 50 different tumor types and making this data freely available to qualified researchers around the world .

By linking the ICGC data with clinical information , ICGCmed aims to accelerate the movement of this information into the clinic to guide prevention , early detection , diagnosis and prognosis , and provide the information needed to match patients ’ disease to the most effective combinations of therapy . ICGCmed research will apply to a broad spectrum of cancers , from early cancers through to metastases .

Source : UC Davis Health System press release , April 17 , 2016 .

The U . S . Food and Drug Administration ( FDA ) approved venetoclax for the treatment of patients with chronic lymphocytic leukemia ( CLL ) who harbor the 17p deletion ( del17p ) and who have received at least one prior therapy . This is the first U . S . FDAapproved treatment that targets the B-cell lymphoma 2 protein . Previously , venetoclax had received orphan drug status for the treatment of CLL and was granted breakthrough therapy designation for the del17p CLL .

The drug ’ s approval was based on the results of a phase II , single-arm clinical trial of 106 patients with del17p CLL . Patients had been treated with a median of 2.5 prior treatments ( range = 1-10 ). Patients received venetoclax 20 mg orally each day , with the dosage increasing to 400 mg over a five-week period .

The overall response rate was 80 percent ( 8 % experienced a complete remission ), with a median time to first response of 0.8 months . After approximately 12 months of follow-up , the median duration of response has yet to be reached .

The most common ( ≥20 %), any-grade adverse events ( AEs ) were neutropenia , diarrhea , nausea , anemia , upper respiratory tract infection , thrombocytopenia , and fatigue . Serious AEs were reported in 44 percent of patients ; the most common ( ≥2 %) were pneumonia , febrile neutropenia , pyrexia , autoimmune hemolytic anemia , anemia , and tumor lysis syndrome .

Patients receiving venetoclax should not be given live attenuated vaccines .

Source : U . S . FDA press release , April 11 , 2016 .

The U . S . FDA approved defibrotide sodium for adults and children with hepatic veno-occlusive disease ( VOD ) with additional kidney or lung abnormalities after they have received hematopoietic cell transplantation ( HCT ). This is the first FDA-approved treatment for severe hepatic VOD . Hepatic VOD is a condition in which some of the veins in the liver become blocked , causing swelling and a decrease in blood flow inside the liver , which may lead to liver damage .

The approval was based on the results of three studies – two prospective clinical trials and one expanded access study – that examined overall survival ( OS ) in 528 patients who had undergone HCT . In the three studies , 38 to 45 percent of patients treated with defibrotide sodium were alive at 100 days post-HCT . Based on published reports and analyses of patientlevel data , the expected survival rates 100 days after HCT would be 21 to 31 percent for patients with severe hepatic VOD who received only supportive care or interventions other than defibrotide , the study researchers noted .

The most common AEs associated with defibrotide sodium include hypotension , diarrhea , vomiting , nausea , and epistaxis . Serious AEs include hemorrhage and allergic reactions .

Patients with bleeding complications or those taking blood thinners or other medications to reduce blood clots should not receive defibrotide sodium .

Source : U . S . FDA press release , March 30 , 2016 .

The National Comprehensive Cancer Network ( NCCN ) released its 2016 Clinical Practice Guidelines in Oncology for Multiple Myeloma , which includes several new treatment options and broadens the management of patients with several plasma cell dyscrasias , including solidary plasmacytoma , smoldering myeloma , multiple myeloma ( MM ), systemic light chain amyloidosis , and Waldenström macroglobulinemia .

The definition of patients with active myeloma is expanded to include patients with :

• > 60 % bone marrow plasmacytosis

• > 100-fold free light chain ratio

• > 1 bone lesion on positron emission tomography or computed tomography of magnetic resonance imaging scanning

Using the revised International Staging System , the NCCN guidelines now include cytogenetics to define prognosis following treatment , which includes serum lactate dehydrogenase and high-risk chromosomal abnormalities ( defined by fluorescence in situ hybridization ) to the serum albumen and beta 2 microglobulin .

The updated guidelines also include , for the first time , the following treatment options for relapsed / refractory MM :

• Carfilzomib , lenalidomide , dexamethasone combination therapy

• Daratumumab

• Ixazomib , lenalidomide , dexamethasone combination therapy

• Elotuzumab with lenalidomide and dexamethasone

• Pomalidomide plus low-dose dexamethasone

• Pomalidomide plus carfilzomib

For both HCT-eligible and transplantineligible patients , the triplet combination therapy of lenalidomide , bortezomib , and dexamethasone is included

as Category 1 treatment for initial MM . Maintenance therapy following induction is also considered “ standard practice ” whether or not the patient proceeds to transplant .

Source : Anderson KC , Alsina M , Atanackovic D . NCCN Guidelines Insights : Multiple myeloma , Version 3.2016 . J Natl Compr Canc Netw . 2016 ; 14:389-400 .

The U . S . FDA granted breakthrough therapy designation for pembrolizumab – a humanized monoclonal anti-PD-1 therapy – for the treatment of patients with relapsed / refractory classic Hodgkin lymphoma .

The designation was granted based on results of the ongoing phase Ib KEY- NOTE-013 and phase II KEYNOTE-087 studies evaluating pembrolizumab as a single-agent therapy for classic Hodgkin lymphoma . In data from KEYNOTE-013 , which were presented at the 2015 ASH Annual Meeting , treatment with pembrolizumab led to an objective response rate ( ORR ) of 64.5 percent in patients with previously treated classic Hodgkin lymphoma . Findings from KEYNOTE-087 are yet to be presented .

This is the fourth breakthrough therapy designation for pembrolizumab . It is also indicated for the treatment of patients with :

• Unresectable or metastatic melanoma

• Metastatic non-small cell lung cancer whose tumors express PD-L1

Source : Merck press release , April 18 , 2016 .