NEWLY APPROVED DRUGS
The Year in FDA Approvals
In 2017 , the U . S . Food and Drug Administration ( FDA ) approved several therapies for the treatment of lymphoid malignancies , including the first two chimeric antigen receptor ( CAR ) T-cell therapies approved for any indication . Below , we review the therapies that became available in the last year .
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 acute lymphocytic leukemia ( ALL ). The agency previously granted inotuzumab ozogamicin priority review and breakthrough-therapy designation .
The safety and efficacy of inotuzumab ozogamicin were evaluated in the randomized , phase III INO-VATE 1022 trial , which enrolled 326 patients who had previously received one or two ALL treatments . Of the 218 evaluated patients , 35.8 percent in the inotuzumab ozogamicin cohort achieved a complete remission ( CR ) for a median of 8.0 months ( range not provided ), compared with 17.4 percent who experienced CR for a median of 4.9 months ( range not provided ) in the alternative chemotherapy cohort .
The most common adverse events ( AEs ) related to inotuzumab ozogamicin include thrombocytopenia , neutropenia , leukopenia , infection , anemia , fatigue , hemorrhage , pyrexia , nausea , headache , and febrile neutropenia . Serious AEs include myelosuppression , infusion-related reactions , and prolonged QT interval .
The drug carries a boxed warning for the risk of severe hepatotoxicity , including veno-occlusive disease and sinusoidal obstruction syndrome . The warning also includes an increased risk of death for patients who take inotuzumab ozogamicin after receiving a hematopoietic cell transplantation .
Tisagenlecleucel
Tisagenlecleucel was approved on August 30 , 2017 , for the treatment of pediatric and young adult patients with B-cell precursor ALL that is refractory or in second or later relapse . This is the first gene therapy available in the U . S . and the first CAR T-cell therapy to receive approval .
The safety and efficacy of tisagenlecleucel ( a CD19-directed CAR T-cell therapy ) were demonstrated in the open-label , phase II ELIANA trial , which included 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL . At three months after infusion , 52 patients ( 83 %) achieved CR or
CR with incomplete blood count recovery .
The most common AEs ( occurring in > 20 % of patients ) were cytokine release syndrome ( CRS ), hypogammaglobulinemia , infections ( pathogens unspecified ), pyrexia , decreased appetite , headache , encephalopathy , hypotension , bleeding episodes , tachycardia , nausea , diarrhea , vomiting , viral infectious disorders , hypoxia , fatigue , acute kidney injury , and delirium .
The drug carries a boxed warning for CRS and neurologic events . Because of the increased risks for these events , tisagenlecleucel was approved with a Risk Evaluation and Mitigation Strategy .
Copanlisib
On September 14 , 2017 , the FDA granted accelerated approval for copanlisib for adults with relapsed follicular lymphoma ( FL ) who have received at least two prior systemic therapies . This is the first approval of an intravenous phosphatidylinositol 3-kinase inhibitor . Copanlisib previously received priorityreview and orphan-drug designations .
The approval was based on results from the single-arm , phase II CHRONOS-1 study , which included people with follicular B-cell non-Hodgkin lymphoma that had relapsed after at least two prior treatments . The overall response rate ( ORR ) among copanlisib-treated patients was 59 percent , with 14 percent achieving a complete response for a median duration of 12.2 months ( range not provided ).
The most common AEs included hyperglycemia , leukopenia , diarrhea , decreased general strength and energy , hypertension , neutropenia , nausea , thrombocytopenia , and lower respiratory tract infections .
Axicabtagene Ciloleucel
On October 18 , 2017 , the FDA approved the CD19-directed CAR T-cell therapy axicabtagene ciloleucel for the treatment of adults with relapsed or refractory large B-cell lymphoma following two or more lines of therapy . The indications include diffuse large B-cell lymphoma ( DLBCL ) not otherwise specified , primary mediastinal large B-cell lymphoma , high-grade B-cell lymphoma , and DLBCL arising from FL .
The safety and efficacy of axicabtagene ciloleucel were demonstrated in the ZUMA-1 trial , in which 101 patients received axicabtagene ciloleucel 2 × 10 6 cells / kg , following conditioning with low-dose cytarabine and fludarabine . The ORR ( assessed by independent central review ) was 72 percent , with a complete response rate of 51 percent . The median duration
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