Literature Scan
( IQR = 0.49-2.79 months ), respectively ( HR = 0.99 ; 95 % CI 0.68-1.43 ; p = 0.94 ). “ Similar overall AE rates were observed with each treatment , and no new safety signals were identified ,” the researchers reported . Forty-four ( 45 %) and 12 ( 26 %) AEs were suspected to be related to study treatment in the eltrombopag and placebo cohorts , respectively ( see TABLE 1 on previous page ).
Thirty-three eltrombopag-treated ( 34 %) and seven placebo-treated ( 15 %) patients had one or more AEs that led to study discontinuation , most often because of sepsis ( n = 5 ) and increased alanine transaminase ( n = 3 ) in the eltrombopag group and general physical health deterioration ( n = 2 ) in the placebo group . Among patients who experienced serious AEs , two in the eltrombopag group were fatal and suspected to be related to treatment ; no serious , fatal AEs were deemed related to placebo .
“ Despite the modest results with respect to platelet transfusion – independence and hematologic improvement , the ASPIRE study suggests that eltrombopag might represent an appropriate monotherapy treatment option for some patients with MDS or AML and thrombocytopenia who have limited therapeutic alternatives ,” the researchers concluded . “ Given the requirement for an effective thrombocytopenia treatment for this high-risk population with expected poor outcomes , ASPIRE and other clinical studies might support the potential for oral eltrombopag monotherapy , … but further research is needed into alternative options .”
The study is limited by its small patient cohorts and limited duration of follow-up . The open-label design also may have introduced bias . Novartis provided funding for the study .
The corresponding authors report financial support from Amgen , Celgene , GlaxoSmithKline , Janssen , Novartis , and Roche . Novartis provided editorial support .
REFERENCE
Mittelman M , Platzbecker U , Afanasyev B , et al . Eltrombopag for advanced myelodysplastic syndromes or acute myeloid leukaemia and severe thrombocytopenia ( ASPIRE ): a randomised , placebo-controlled , phase 2 trial . Lancet Haematol . 2017 December 11 . [ Epub ahead of print ]
38 ASH Clinical News
Long-Term FOLL05-Up : R-CHOP Best for Advanced-Stage FL
In 2005 , the FOLL05 trial sought to determine the optimal immunochemotherapy ( ICT ) regimen for firstline treatment of advanced-stage follicular lymphoma ( FL ): R-CVP ( rituximab , cyclophosphamide , vincristine , prednisone ), R-CHOP ( rituximab , cyclophosphamide ,
The first FDA-approved
CAR-T cell therapy
Child portrayed is not a real KYMRIAH patient .
CONTRAINDICATIONS None
KYMRIAH
CAR-
TRANSFORM TREATMENT
IMPORTANT SAFETY INFORMATION FOR KYMRIAH doxorubicin , vincristine , prednisone ), or R-FM ( rituximab , fludarabine , mitoxantrone ).
After a median follow-up of 84 months ( range = 1-119 months ), patients with advanced-stage FL experienced an eight-year progression-free survival
TRANSFORM TOMORROW
INDICATION
KYMRIAH™ ( tisagenlecleucel ) is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia ( ALL ) that is refractory or in second or later relapse .
WARNING : CYTOKINE RELEASE SYNDROME AND NEUROLOGICAL TOXICITIES
• Cytokine Release Syndrome ( CRS ), including fatal or life-threatening reactions , occurred in patients receiving KYMRIAH . Do not administer KYMRIAH to patients with active infection or inflammatory disorders . Treat severe or life-threatening CRS with tocilizumab .
• Neurological toxicities , which may be severe or life-threatening , can occur following treatment with KYMRIAH , including concurrently with CRS . Monitor for neurological events after treatment with KYMRIAH . Provide supportive care as needed .
• KYMRIAH is available only through a restricted program under a Risk Evaluation and Mitigation Strategy ( REMS ) called the KYMRIAH REMS .
WARNINGS AND PRECAUTIONS Cytokine Release Syndrome : CRS , including fatal or life-threatening reactions , occurred following treatment with KYMRIAH . In Study 1 , CRS occurred in 79 % ( 54 / 68 ) of patients receiving KYMRIAH , including grade 3 or 4 ( Penn grading system ) CRS in 49 % ( 33 / 68 ) of patients . The median time to onset of CRS was 3 days ( range : 1-22 days ). Of the 54 patients with CRS , 27 ( 50 %) received tocilizumab ; 7 ( 13 %) patients received 2 doses of tocilizumab , 3 ( 6 %) patients received 3 doses of tocilizumab and 14 ( 26 %) patients received addition of corticosteroids ( e . g . methylprednisolone ). The median time to resolution of CRS was 8 days ( range : 1-36 days ).
Key manifestations of CRS may include high fever , lower than normal blood pressure , difficulty breathing , and may be associated with hepatic , renal , and cardiac dysfunction , and coagulopathy . Risk factors for severe CRS are high pre-infusion tumor burden , uncontrolled or accelerating tumor burden following lymphodepleting chemotherapy , active infections , and / or inflammatory processes . Delay KYMRIAH infusion after lymphodepleting chemotherapy if patient has unresolved serious adverse reactions from preceding chemotherapies , active uncontrolled infection , active graft vs host disease , or worsening of leukemia burden .
Ensure tocilizumab is available on-site prior to KYMRIAH infusion . Monitor patients for signs or symptoms of CRS for at least 4 weeks after treatment . Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur . At the first sign of CRS , immediately evaluate the patient for hospitalization and institute treatment with supportive care , tocilizumab and / or corticosteroids as indicated .
Neurological Toxicities : Neurological toxicities , which may be severe or life-threatening , can occur following treatment with KYMRIAH . The majority of neurological toxicities occurred within 8 weeks following KYMRIAH infusion . In Study 1 , neurological toxicities within 8 weeks after KYMRIAH infusion occurred in 65 % of patients , including grade 3 or 4 neurological toxicities in 18 % of patients , and 75 % of events resolved within 12 days . The most common neurological toxicities were headache ( 37 %), encephalopathy ( 34 %), delirium ( 21 %), anxiety ( 13 %), and tremor ( 9 %). Other manifestations of neurological toxicities included disturbances in consciousness , disorientation , confusion , agitation , seizures , mutism and aphasia . Monitor patients for neurological events and exclude other causes for symptoms . Provide supportive care as needed for KYMRIAH-associated neurological events .
Please see Brief Summary of Prescribing Information , including Boxed WARNING , and additional Important Safety Information for KYMRIAH on following pages .