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CLINICAL PEARLS (continued)
As with blinatumomab, the severity of CRS following CAR T kg/day of methylprednisolone given at the peak of CRS for short
cells is related to disease burden prior to treatment, in addition intervals is unlikely to impair CAR T-cell efficacy, yet more clinical
to possible associations with the dose of T cells infused and the experience is needed to make a definitive statement regarding the
schedule of cell infusion (100% of target dose infused on day 1 ver- effects of steroids on CAR T-cell efficacy.16 Dexamethasone may
sus administered over 3 days).8,17 The presence of any grade of CRS be preferred over methylprednisolone in the setting of neurologic
following CAR T cells correlates with antitumor effect; however, it toxicity given its greater blood-brain barrier penetration.16
is unclear if patients experiencing severe CRS demonstrate greater
antitumor efficacy than those with lower grade CRS.16 Grade 3 CRS is a complicated and unique toxicity following blinatumomab
CRS following CAR T cells (or grade 2 CRS in an older patient with and CAR T cells, which are two major therapeutic advances in the
comorbidities) is managed with the IL-6 receptor antagonist tocili- management of RR B-ALL. Grade 1–2 CRS is typically managed with
zumab at 8 mg/kg IV administered over 1 hour.16 Targeting IL-6 supportive care, with a low threshold to administer dexamethasone
has become the most common management strategy for moderate in the case of progressive CRS with blinatumomab. Minimal pub-
to severe CRS following CAR T cells due to early clinical experience, lished experience exists for tocilizumab in blinatumomab-related
rapid onset of efficacy, favorable tolerability, and lack of apparent CRS, and thus should be reserved for steroid-refractory CRS. The
detrimental effect on antitumor efficacy (although this remains cornerstone of CRS management following CAR T cells is tocili-
experimental and expert opinion in the absence of randomized zumab. Our practice is to deliver tocilizumab within 15 minutes
data).16 Following tocilizumab, clinical improvement can occur of order entry, with a low threshold to repeat dosing in the setting
quickly (within a few hours), yet some patients with suboptimal of suboptimal response. Siltuximab and ultimately high-dose
response may require an additional dose of tocilizumab within corticosteroids are options for tocilizumab-refractory CRS fol-
several hours of the first dose.18 The IL-6 antagonist siltuximab, lowing CAR T cells. Further research is needed to determine the
administered over 1 hour at 11 mg/kg, also is an option for CRS effects of high-dose steroids on the clinical efficacy of CAR T cells.
refractory to tocilizumab, but the benefit of this addition remains Pharmacists working in centers using blinatumomab and investi-
unclear.16,18 A hallmark of CAR T-cell CRS management has been gational CAR T cells must understand the intricacies of this unique
to limit use of corticosteroids in the first-line setting given the po- AE and be prepared to recommend supportive care despite limited
tential to dampen CAR T-cell efficacy due to the T-cell lymphotoxic clinical experience to maximize patient outcomes with these novel
effect of steroids. On the contrary, recent data suggest up to 2 mg/ therapeutic agents.
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