MEETING NEWS
Highlights from the 2019 ASH Annual Meeting
limited-stage disease have better overall survival (OS)
than those with advanced-stage disease, they can expe-
rience late relapses regardless of treatment strategy.
While National Comprehensive Cancer Network
guidelines recommend these patients receive abbre-
viated R-CHOP followed by radiation therapy, recent
research has suggested that certain patients who have a
negative PET scan after 3 cycles of chemotherapy may
be able to skip radiation therapy. In the S1001 study,
Dr. Persky and investigators evaluated this approach in
patients with newly diagnosed, stage I or II, non-bulky
(< 10 cm in greatest diameter) DLBCL. Patients with
CNS lymphoma, testicular lymphoma, primary medi-
astinal B-cell lymphoma, and concurrent or preceding
indolent lymphoma were excluded. All participants
received standard R-CHOP therapy, then had an inter-
im PET scan performed on days 15 through 18 of cycle
3. If the PET scan was negative (defined as a Deauville
score 1-3), patients proceeded with 1 additional cycle
of R-CHOP; if the PET scan was positive (Deauville
score 4-5), patients received involved-field radiation
therapy (IFRT) within 5 weeks, followed by ibritumomab
tiuxetan.
Initially, 159 patients were enrolled, but 1 was up-
staged by PET and 26 were considered ineligible due to
incorrect histology (n=21), no specimen submitted (n=3),
and bulky bone disease (n=2).
The 132 remaining evaluable patients (median age
= 62 years; range = 18-86) proceeded with 3 cycles of
R-CHOP. Of these patients, 62% (n=82) had stage I
disease. The median largest diameter on imaging was
3.5 cm (range = 1.0-9.7 cm); 43% of patients (n=57)
had extranodal involvement, while 66% (n=87) had
involvement only with head and neck. Stage-modified
international prognostic index (smIPI) was 0 in 27% of
patients, I in 42%, II in 28%, and III in 4% of patients.
The study population also included 4 patients (3%)
with double-hit lymphoma (DHL), either MYC/BCL2
(n=2) or MYC/BCL6 (n=2).
Prior to PET scan, 4 patients went off treatment,
leaving 128 patients who underwent PET scans. Upon
central review, 110 patients were considered PET-negative
and 18 were PET-positive. Dr. Persky noted that, of the
PET-positive patients, 4 were due to infection (Deau-
ville X) and so were treated as having a PET-negative
scan. One patient in the PET-negative arm died, so 113
patients continued R-CHOP per study protocol.
In the “truly PET-positive” group, 2 patients refused
radiation, and the 12 remaining patients received
per-protocol IFRT plus ibritumomab tiuxetan.
During a median follow-up of 4.5 years (range =
1.1-7.5), only 5 patients had progressive disease: 3 who
received 4 cycles of R-CHOP, 1 who was PET-positive
but declined radiation, and 1 who went off treatment
after the first cycle of R-CHOP.
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Focus on Lymphoid & Plasma Cell Malignancies
Two study participants died from lymphoma, while
11 patients died from non-lymphoma causes (including
1 PET-negative patient who died from secondary acute
myeloid leukemia and another who died of lung adeno-
carcinoma that was diagnosed via PET scan). Dr. Persky
pointed out that the patients in the latter group were
older, with a median age of 80 years.
Overall, survival outcomes were similar between
PET-negative and PET-positive patients, confirming the
authors’ hypothesis that PET-directed therapy would
improve survival by guiding intensity of treatment
based on risk. The 5-year progression-free survival (PFS;
primary endpoint) and OS rates for PET-positive and
PET-negative patients, respectively, were:
• PFS: 86% vs. 88%
• OS: 93% vs. 91%
This compared favorably with the historical 5-year PFS
for patients with limited-stage DLBCL, which has been
reported at 85%, Dr. Persky said. He added that survival
outcomes appeared to differ according to disease stage
at enrollment. For example, patients with smIPI stage 0
had a 5-year PFS of 97%, stage I and II had a 5-year PFS
of 86%, and stage III had a 5-year PFS of 30%. At the
time of data presentation, all 4 patients with “dou-
ble hit” lymphoma (DHL) had disease that was still in
remission.
Together with results from the FLYER trial, which
suggested that younger patients with favorable-prognosis
limited stage disease can achieve similarly high 5 year
PFS and OS rates with 4 cycles of R-CHOP plus two cycles
of rituximab monotherapy as with 6 cycles of R-CHOP,
“this NCTN trial establishes four cycles of R-CHOP alone
as the new standard approach to limited-stage disease
for the majority of patients,” Dr. Persky said. 2 He noted,
however, that because of the small number of lymphoma
events, the researchers were unable to draw conclusions
about the prognostic ability of scoring systems like smIPI
or lymphoma subtype. ●
The authors report no relevant conflicts of interest.
References
1. Persky D, Li H, Stephens D, et al. PET-directed therapy for patients with limited-stage
diffuse large B-cell lymphoma - results of intergroup NCTN Study S1001. Abstract #626.
Presented at the 2019 American Society of Hematology Annual Meeting, December 8, 2019;
Orlando, FL.
2. Poeschel V, Held G, Ziepert M, et al. Four versus six cycles of CHOP chemotherapy in
combination with six applications of rituximab in patients with aggressive B-cell lymphoma
with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet.
2020;394:2271-2281.