Literature Scan
Early Evidence Suggests PD-1 Inhibitors May Be Effective
in Relapsed/Refractory Mediastinal Gray-Zone Lymphoma
Mediastinal gray-zone lymphoma, nodu-
lar sclerosis classic Hodgkin lymphoma
(cHL), and primary mediastinal B-cell
lymphoma have overlapping clinical,
histologic, and molecular features,
including the frequency of 9p24.1
copy-number alterations associated
with susceptibility to immune check-
point inhibition. Such alterations
occur in approximately 61 percent of
patients with mediastinal gray-zone
lymphoma, which is typically resis-
tant to treatment.
In a Letter to the Editor published
in the New England Journal of
Medicine, Christopher Melani, MD,
of the National Cancer Institute in
Bethesda, Maryland, and colleagues
noted “recent findings indicate that
mediastinal gray-zone lymphoma may
be more closely related to cHL than to
primary mediastinal B-cell lymphoma”
and therefore may respond to immune
checkpoint inhibition.
Dr. Melani described three case
studies that demonstrate “early
evidence for using PD-1 inhibition
[with agents like nivolumab and
pembrolizumab] in relapsed or
refractory mediastinal gray-zone
lymphoma.”
• Case 1: An 18-year-old woman
with mediastinal gray-zone
lymphoma (confirmed after a
biopsy of a mediastinal mass
showed an immunophenotype
intermediate between diffuse large
B-cell lymphoma [DLBCL] and
cHL, which was positive for CD20,
CD30, and CD15) experienced a
partial response (PR) to dose-
adjusted etoposide, doxorubicin,
and cyclophosphamide with
vincristine and prednisone plus
rituximab (DA-EPOCH-R).
However, six weeks after salvage
radiotherapy, her disease
progressed. She was then treated
with pembrolizumab and had
a complete metabolic response
(defined as normalization of
an abnormal positron emission
tomography scan). After 235
days of treatment, she underwent
allogeneic hematopoietic cell
transplantation. Fluorescence in
situ hybridization (FISH) detected
rearrangement of the genes
encoding the PD-1 and PD-2
ligands.
• Case 2: A 76-year-old man
with mediastinal gray-zone
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ASH Clinical News
lymphoma (confirmed after a biopsy
of a subcarinal mass showed DLBCL
with an immunophenotype of cHL,
which was positive for CD30 and
PAX5 and negative for CD10, CD20,
and CD15) also experienced a PR
to DA-EPOCH-R, but his disease
subsequently progressed. After
treatment with pembrolizumab, he
had a complete metabolic response
and continues to be in remission after
381 days of treatment. FISH detected
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