NEWLY APPROVED DRUGS
The Year in FDA Approvals
The excitement over immunotherapy for cancer treatment shows no signs of waning , with several agents approved by the U . S . Food and Drug Administration ( FDA ) this year . Below is a list of immunotherapies that were recently approved by the FDA for the treatment of hematologic conditions or whose indications were expanded .
Leukemia Tisagenlecleucel : On August 30 , 2017 , the chimeric antigen receptor ( CAR ) T-cell therapy tisagenlecleucel for the treatment of pediatric and young adult patients with B-cell precursor acute lymphocytic leukemia ( ALL ) that is refractory or in second or later relapse became the first FDA-approved gene therapy available in the United States . The drug carries a boxed warning for cytokine release syndrome ( CRS ) and neurologic events and , because of these risks , the drug was approved with a Risk Evaluation and Mitigation Strategy . On the same day as the approval , the FDA also expanded the indication for tocilizumab , a monoclonal antibody to treat CAR T-cell – induced , severe or life-threatening CRS in patients ≥2 years of age . ( For more about CAR T-cell therapy for hematologic malignancies , see “ Entering A New Era of Immunotherapy ” on page 4 .)
Gemtuzumab ozogamicin : On September 1 , 2017 , the FDA approved gemtuzumab ozogamicin ( GO ), a recombinant anti- CD33 drug conjugate , for the treatment of CD33-positive acute myeloid leukemia ( AML ). The agent was originally approved under the FDA ’ s accelerated approval program in 2000 , but the manufacturer voluntarily withdrew the drug in 2010 following reports of adverse events and failure of the drug to show improvement in complete response ( CR ) rate , disease-free survival , or overall survival ( OS ) when combined with induction and consolidation chemotherapy for younger adults with AML in the Southwest Oncology Group S0106 phase III clinical trial . The present recommendation is based on results from the phase III ALFA-0701 trial , which evaluated GO in combination with daunorubicin for the treatment of de novo AML . At three-year follow-up , patients treated with GO had a longer median eventfree survival ( EFS ) than patients who received chemotherapy alone ( 17.3 months vs . 9.5 months ; p value not reported ). The label contains a boxed warning for hepatotoxicity .
Inotuzumab ozogamicin : On August 17 , 2017 , the FDA approved inotuzumab ozogamicin , an anti-CD22 monoclonal antibody for the treatment of adults with relapsed or refractory B-cell precursor ALL . Previously , the FDA granted the drug priority review , as well as orphan-drug and breakthrough-therapy designations . Approval was based on data from the INO-VATE ALL trial , in which patients with Philadelphia chromosome ( Ph )– positive or – negative relapsed or refractory B-cell precursor ALL were randomized to receive either inotuzumab ozogamicin ( n = 164 ) or investigator ’ s choice of chemotherapy ( n = 162 ). In the inotuzumab arm , 35.8 percent of patients achieved complete remission , lasting for a median of eight months ( range not provided ). Also , 89.7 percent of responders were negative for minimal residual disease ( MRD ). In the investigator-choice arm , only 17.4 percent of patients achieved complete remission , lasting a median of 4.9 months , and 31.6 percent were MRD negative . The drug carries a boxed warning for hepatotoxicity and an increased risk of death for use after a hematopoietic cell transplantation .
Blinatumomab : The bispecific T-cell engager blinatumomab received accelerated approval in December 2014 for the treatment of Ph-negative relapsed or refractory B-cell precursor ALL , and , on July 11 , 2017 , the FDA granted regular approval to blinatumomab for the treatment of relapsed or refractory B-cell precursor ALL in adults and children . The supplemental approval confirms clinical benefit required under accelerated approval and expands the indication to include Ph-positive relapsed or refractory B-cell precursor ALL . Clinical benefit was confirmed in the TOWER trial , in which blinatumomab lengthened OS , compared with standard-of-care chemotherapy ( 7.7 months vs . 4.0 months ; p = 0.012 ). The decision to expand the approval to patients with Ph-positive ALL was based on results from the ALCANTARA trial , in which 36 percent of patients with disease that was resistant or intolerant to treatment with second-generation tyrosine kinase inhibitors achieved a complete remission with complete or partial hematologic recovery .
Lymphoma Rituximab and hyaluronidase combination : On June 22 , 2017 , the FDA approved the subcutaneous injection formula of rituximab and hyaluronidase for the treatment of adults with relapsed or refractory , previously untreated , or stable follicular lymphoma ; previously untreated diffuse large B-cell lymphoma ; or previously untreated or previously treated chronic lymphocytic leukemia . The approval offers patients a subcutaneous route of rituximab administration that shortens administration time from several hours to five to seven minutes . The approval was based on multiple randomized clinical trials in which rituximab and hyaluronidase demonstrated rituximab trough concentration levels that were non-inferior to intravenous ( IV ) rituximab 375 mg / m 2 and IV rituximab 500 mg / m 2 . Efficacy and safety outcomes were also comparable between the two products .
Pembrolizumab : On March 15 , 2017 , the FDA granted accelerated approval to pembrolizumab , an anti-PD-1 monoclonal antibody , for adults and children with classic Hodgkin lymphoma that is refractory to treatment or has relapsed after three or more prior lines of therapy . This is the only anti-PD-1 therapy approved for this population . The approval was based on results from the KEYNOTE-087 trial , which included patients who received pembrolizumab 200 mg every three weeks . After a median follow-up of 9.4 months , the overall response rate was 69 percent ( 95 % CI 62-75 ), which included a complete remission rate of 22 percent and a partial remission rate of 47 percent . The median duration of response was 11.1 months ( range = 0-11.1 months ). ●
2 Focus on Immunotherapy