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Advances in Aggressive Lymphoma from the 2017 American Society Of February 2018 Volume 16, Issue 2, Supplement 5 A SPECIAL MEETING REVIEW EDITION Advances in Aggressive Lymphoma From the 2017 American Society of Hematology Annual Meeting and Exposition A Review of Selected Presentations From the 2017 American Society of Hematology Annual Meeting and Exposition • December 9-12, 2017 • Atlanta, Georgia Special Reporting on: • Long-Term Follow-Up of ZUMA-1: A Pivotal Trial of Axicabtagene Ciloleucel (Axi-Cel; KTE-C19) in Patients With Refractory Aggressive Non-Hodgkin Lymphoma • Primary Analysis of JULIET: A Global, Pivotal, Phase 2 Trial of CTL019 in Adult Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma • A Comparison of One Year Outcomes in ZUMA-1 (Axicabtagene Ciloleucel) and SCHOLAR-1 in Patients With Refractory, Aggressive Non-Hodgkin Lymphoma • High Durable CR Rates in Relapsed/Refractory (R/R) Aggressive B-NHL Treated With the CD19-Directed CAR T Cell Product JCAR017 (TRANSCEND NHL 001): Defined Composition Allows for Dose-Finding and Definition of Pivotal Cohort • Phase 1 Results From ZUMA-6: Axicabtagene Ciloleucel (axi-cel; KTE-C19) in Combination With Atezolizumab for the Treatment of Patients With Refractory Diffuse Large B-Cell Lymphoma • Effect of Rituximab in Primary Central Nervous System Lymphoma—Results of the Randomized Phase III HOVON 105/ALLG NHL 24 Study • Encouraging Early Results From the First in-Human Clinical Trial of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/ Refractory B-Cell Lineage Non-Hodgkin Lymphoma PLUS Meeting Abstract Summaries With Expert Commentary by: Frederick L. Locke, MD Vice Chair and Associate Member Department of Blood and Marrow Transplant and Cellular Immunotherapy Moffitt Cancer Center Tampa, Florida ON THE WEB: hematologyandoncology.net Indexed through the National Library of Medicine (PubMed/MEDLINE), PubMed Central (PMC), and EMBASE IMPORTANT SAFETY INFORMATION (continued) SERIOUS INFECTIONS Severe or life-threatening infections occurred in patients after YESCARTA™ infusion. CYTOKINE RELEASE SYNDROME (CRS) In Study 1, infections (all grades) occurred in 38% of patients. Grade 3 or higher CRS, including fatal or life-threatening reactions, occurred following treatment infections occurred in 23% of patients. Grade 3 or higher infections with an unspecified with YESCARTA™. In Study 1, CRS occurred in 94% (101/108) of patients receiving pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections YESCARTA™, including ≥ Grade 3 (Lee grading system) CRS in 13% (14/108) of in 4%. YESCARTA™ should not be administered to patients with clinically significant patients. Among patients who died after receiving YESCARTA™, four had ongoing active systemic infections. Monitor patients for signs and symptoms of infection before CRS events at the time of death. The median time to onset was 2 days (range: and after YESCARTA™ infusion and treat appropriately. Administer prophylactic anti- 1 to 12 days) and the median duration of CRS was 7 days (range: 2 to 58 days). microbials according to local guidelines. Key manifestations of CRS include fever (78%), hypotension (41%), tachycardia Febrile neutropenia was observed in 36% of patients after YESCARTA™ infusion (28%), hypoxia (22%), and chills (20%). Serious events that may be associated and may be concurrent with CRS. In the event of febrile neutropenia, evaluate with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular for infection and manage with broad spectrum antibiotics, fluids and other tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak supportive care as medically indicated. syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/ macrophage activation syndrome (HLH/MAS) [see Adverse Reactions (6)]. Viral Reactivation Ensure that 2 doses of tocilizumab are available prior to infusion of YESCARTA™. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, Monitor patients at least daily for 7 days at the certified healthcare facility hepatic failure and death, can occur in patients treated with drugs directed against B following infusion for signs and symptoms of CRS. Monitor patients for signs or cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines symptoms of CRS for 4 weeks after infusion. Counsel patients to seek immediate before collection of cells for manufacturing. medical attention should signs or symptoms of CRS occur at any time [see PROLONGED CYTOPENIAS Patient Counseling Information (17)]. At the first sign of CRS, institute treatment Patients may exhibit cytopenias for several weeks following lymphodepleting with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated chemotherapy and YESCARTA™ infusion. In Study 1, Grade 3 or higher [see Dosage and Administration (2.3)]. cytopenias not resolved by Day 30 following YESCARTA™ infusion occurred in NEUROLOGIC TOXICITIES 28% of patients and included thrombocytopenia (18%), neutropenia (15%), and INTRODUCING A NEW Neurologic toxicities, that were fatal or life-threatening, occurred following anemia (3%). Monitor blood counts after YESCARTA™ infusion. treatment with YESCARTA™. Neurologic toxicities occurred in 87% of patients. HYPOGAMMAGLOBULINEMIA Ninety-eight percent of all neurologic toxicities occurred within the first 8 weeks B-cell aplasia and hypogammaglobulinemia can occur in patients receiving of YESCARTA™ infusion, with a median time to onset of 4 days (range: 1 to 43 treatment with YESCARTA™. In Study 1, hypogammaglobulinemia occurred in 15% days). The median duration of neurologic toxicities was 17 days. Grade 3 or higher of patients. Monitor immunoglobulin levels after treatment with YESCARTA™ and neurologic toxicities occurred in 31% of patients. manage using infection precautions, antibiotic prophylaxis and immunoglobulin CAR T THERAPY The most common neurologic toxicities included encephalopathy (57%), replacement. headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), The safety of immunization with live viral vaccines during or following insomnia (9%) and anxiety (9%). Prolonged encephalopathy lasting up to 173 days YESCARTA™ treatment has not been studied. Vaccination with live virus vaccines was noted. Serious events including leukoencephalopathy and seizures occurred is not recommended for at least 6 weeks prior to the start of lymphodepleting Find a list of authorized treatment centers with YESCARTA™. Fatal and serious cases of cerebral edema have occurred in chemotherapy, during YESCARTA™ treatment, and until immune recovery patients treated with YESCARTA™. following treatment with YESCARTA™. at YESCARTA.com/centers Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of neurologic toxicities. Monitor SECONDARY MALIGNANCIES patients for signs or symptoms of neurologic toxicities for 4 weeks after infusion Patients treated with YESCARTA™ may develop secondary malignancies. Monitor and treat promptly [see Management of Severe Adverse Reactions (2.3); Neurologic life-long for secondary malignancies. In the event that a secondary malignancy Toxicities]. occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient INDICATION samples to collect for testing. YESCARTA™ REMS YESCARTA™ is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult Because of the risk of CRS and neurologic toxicities, YESCARTA™ is available EFFECTS ON ABILITY TO DRIVE AND USE MACHINES patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large only through a restricted program under a Risk Evaluation and Mitigation Due to the potential for neurologic events, including altered mental status or B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, Strategy (REMS) called the YESCARTA™ REMS [see Boxed Warning and Warnings seizures, patients receiving YESCARTA™ are at risk for altered or decreased and DLBCL arising from follicular lymphoma. and Precautions (5.1 and 5.2)]. The required components of the YESCARTA™ REMS consciousness or coordination in the 8 weeks following YESCARTA™ infusion. Limitation of Use: YESCARTA™ is not indicated for the treatment of patients with primary central nervous system lymphoma. are: Advise patients to refrain from driving and engaging in hazardous occupations • Healthcare facilities that dispense and administer YESCARTA™ must be or activities, such as operating heavy or potentially dangerous machinery, during IMPORTANT SAFETY INFORMATION enrolled and comply with the REMS requirements. Certified healthcare this initial period. facilities must have on-site, immediate access to tocilizumab, and ensure ADVERSE REACTIONS WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES that a minimum of two doses of tocilizumab are available for each patient for The most common adverse reactions (incidence ≥ 20%) include CRS, fever, • Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving infusion within 2 hours after YESCARTA™ infusion, if needed for treatment of hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, YESCARTA™. Do not administer YESCARTA™ to patients with active infection or inflammatory
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