Literature Scan
1×10 6 dose level (n=11; p<0.001). “The data provided
no evidence to suggest that previous chemotherapy or
CD19-based immunotherapy diminishes the likelihood
of remission induction following administration of bio-
active doses of CD22 CAR T cells,” the authors reported,
with nine of 10 anti-CD19 CAR T-cell–treated patients
experiencing CR.
The researchers detected anti-CD22 CAR T cells in the
peripheral blood of 19 treated patients, which peaked by
day 14 after infusion. The median peak expansion was 62
percent of circulating T cells expressing CD22 CAR (range
= 1-91%), and the median number of
circulating CAR T cells was 316 cells/µL
(range = 1-3,593 cells/µL).
“These results
are the first to
establish that
CAR T cells
targeting
antigens other
than CD19
can mediate
similarly potent
antineoplastic
effects ... open-
ing the way for
dual-targeted
immuno-
therapeutics.”
—TERRY J. FRY, MD
By day 28, CAR T cells remained
detectable in the peripheral blood in 15
of 21 patients (72%), in the bone marrow
in 15 of 19 patients (79%), and in the
cerebrospinal fluid in 12 of 17 patients
(71%). CAR T cells remained detectable
in the blood of seven of nine patients
evaluable at three months post-infusion,
in two of three patients at six months, in
one patient evaluable at nine months, and
in one patient evaluable at 18 months.
Remission lasted for a median of six
months (range not provided), with eight
patients relapsing at 1.5 to 12 months
after infusion. Most of those who
relapsed had leukemia cells that had
diminished CD22 surface expression
(n=7). The researchers also found that
10 of the 15 patients previously treated
with CD19-targeted CAR T-cell therapy
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ASH Clinical News
no longer expressed any CD19, suggesting that antigen loss
limits treatment efficacy.
“These results are the first to establish that CAR T cells
targeting antigens other than CD19 can mediate similarly
potent antineoplastic effects,” the authors concluded. The find-
ings also “demonstrate that resistance to immunotherapy
via antigen loss can be overcome by treatment with CAR T
cells targeting an alternative antigen, opening the way for
dual-targeted immunotherapeutics.”
This phase I study is limited by its small patient popula-
tion. “Future studies are needed to determine whether the
high response rates observed with CD22 CARs in B-ALL
will translate into similarly sizeable response rates in dif-
fuse large B-cell lymphoma, in which CD22 expression is
common,” the authors noted.
Two of the authors are inventors on a patent for the CD22-
directed CAR T-cell therapy.
REFERENCES
• Fry TJ, Shah NN, Orentas RJ, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or
resistant to CD19-targeted CAR immunotherapy. Nat Med. 2017 November 20. [Epub ahead of print]
• Stanford Medicine press release, November 20, 2017.