CAR T-Cell Therapy
found that other patients with CRS also have sky-high levels of IL-6 .”
Once Emily was treated with tocilizumab ( an antibody against the IL-6 receptor used primarily to treat rheumatoid arthritis ), her symptoms rapidly reversed .
“ It was incredibly fortuitous for her , and for the whole field , that tocilizumab was utterly transformative for treating severe CRS ,” said Dr . Grupp . “ Without the ability to block IL-6 , I don ’ t think we could safely give these cells to patients .”
The drug is now part of the standard toxicity
management protocol , and it works with all three available CAR T-cell therapies . Dr . Grupp stressed , however , that the side effects of CAR T cells shouldn ’ t be minimized ; they require sophisticated ICU-level care and an experienced team to manage them , which may limit the number of centers able to administer the treatment .
While cytokine blockade with tocilizumab is effective in reversing CRS , it does not prevent expansion of CAR T cells or reduce their anti-leukemic efficacy .
Dr . Goff has found neurotoxicity to be a bigger issue than CRS , maybe , she speculated , because , “ in leukemia ,
the cell being targeted is freely circulating in the blood and marrow , which may make CRS more evident . In lymphoma , the targets are solid masses , rather than cells floating around in the blood .”
In the latest trial of CAR T-cell therapy conducted at NCI , only three patients ( of 19 ) required any sort of vasoactive medication to counteract CRS , while about half experienced grade 3 or 4 neurotoxicity . 4 “ We ’ ve seen a range of neurotoxicity , varying from mild confusion and word-finding issues to frank encephalopathy , hallucinations , seizures , and extreme agitation ,” she said .
Expanding CAR T-Cell Therapy to Myeloma
At the 2016 ASH Annual Meeting , Adam D . Cohen , MD , from the University of Pennsylvania in Philadelphia , and colleagues presented preliminary safety and efficacy results from an ongoing , phase I study of CAR T cells engineered to target B-cell maturation antigen ( a protein expressed on myeloma cells ) in nine patients with relapsed / refractory myeloma .
“ These patients had few other options – having received a median of nine prior lines of therapy for their myeloma ,” Dr . Cohen told ASH Clinical News .
The complete remission rate was 44 percent , including one patient who has been in stringent complete remission for 12 months . “ This patient was heavily pretreated , having received 11 prior lines of treatment ,” Dr . Cohen noted .
Eight of nine patients developed cytokine release syndrome ( CRS ), which is a well-known toxicity of CAR T-cell therapies . Though most cases were mild ( grade 1 or grade 2 ), three patients developed severe CRS . However , CRS in these patients was successfully managed with the IL-6 receptor tocilizumab , the authors wrote .
Two patients experienced neurotoxicity , which also has been described in other studies of CAR T-cell therapy . “ One of the patients developed severe encephalopathy with edema of the brain ,” Dr . Cohen explained . “ Fortunately , this patient recovered after treatment with steroids and cyclophosphamide . Still , this is a significant toxicity , and we need a better understanding of how it develops and how to prevent it .”
“ Accrual for the first cohort is complete , and we are now enrolling patients in the next cohorts , in which patients will undergo lymphodepletion with cyclophosphamide before being given the CAR T-cell infusion ,” Dr . Cohen said . “ We are hoping this will enhance the expansion and persistence of these cells and improve the overall response rate .”
To watch the full interview with Dr . Cohen , visit ashclinicalnews . org / multimedia . For more coverage of the 2016 ASH Annual Meeting , turn to page 22 .
AML is swarming with challenges
Impact of disease
• Acute myeloid leukemia ( AML ) is the most common type of leukemia in adults , accounting for approximately 25 % of leukemia diagnoses , with an estimated 19,950 new cases in the United States this year 1 , 2
• The 5-year survival rate in patients with AML is about 26 % 1
• An estimated 10,430 patients will die from AML this year 1
AML evolves rapidly because of its polyclonal and heterogeneous features , contributing to the clinical challenges of this disease 3
• As indicators of prognosis , cytogenetic and molecular mutation testing are recommended by the National Comprehensive Cancer Network ® ( NCCN ® ) at diagnosis 4
• Evaluation of molecular mutations may be important for risk assessment and prognosis to help guide treatment decisions 4
32 ASH Clinical News