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PAPER SPOTLIGHT
Is “Watching and Waiting” Enough for Patients
With Nodular Lymphocyte-Predominant
Hodgkin Lymphoma?
For patients with nodular
lymphocyte-predominant Hodgkin
lymphoma (NLPHL), active sur-
veillance appeared to be a feasible
initial management strategy, ac-
cording to an analysis published in
Blood by researchers at Memorial
Sloan Kettering Cancer Center
(MSKCC). Furthermore, NLPHL,
which comprises just 5% of
Hodgkin lymphoma cases, has an
excellent prognosis regardless of
treatment strategy, corresponding
author David J. Straus, MD, told
ASH Clinical News.
“Opinions differ about initial
management of patients diag-
nosed with NLPHL [because]
many patients present with local
disease and are treated with
radiation therapy or with com-
bined modality treatment with
chemotherapy and radiotherapy,”
he explained. “Patients with more
advanced disease are treated with
systemic treatments including
chemotherapy, rituximab alone,
or rituximab in combination with
chemotherapy.”
In this report, the researchers
retrospectively analyzed treat-
ment outcomes for 163 patients
(median age = 40 years; range
= 16-75 years) who were newly
diagnosed with NLPHL between
1974 and 2016.
“Because of the frequent
indolent course of NLPHL and the
question of whether interventions
affect ultimate outcome, we have
adopted a conservative approach
at MSKCC, like that for low-grade
non-Hodgkin lymphoma (NHL),
with active surveillance of pa-
tients presenting with low tumor
bulk and without symptoms,” he
added. “For such patients, the
important question may be ‘when
and if,’ rather than ‘what.’ In our
retrospective experience, 23% of
patients were successfully man-
aged with this approach and had
excellent outcomes.”
Management strategies, deter-
mined by the treating physicians,
in the entire cohort were:
• radiotherapy alone (46%)
• active surveillance (23%)
• chemotherapy (16%)
• combined modality (12%)
• rituximab monotherapy (4%)
Primary outcomes included
progression-free survival (PFS;
defined as time from diagnosis to
biopsy-proven disease progres-
sion, initiation of additional
treatment, or death from any
cause) and second PFS (PFS2;
defined as time from disease
progression to relapse to second
biopsy-proven disease progres-
sion, second initiation of further
treatment, or death from any
cause). Rates of transformation,
secondary malignancies, and
death (associated with or not
associated with lymphoma) were
also evaluated throughout the
study period.
Most patients (74%) had stage
I/II disease, including 23 of the 37
patients (62%) who received active
surveillance. Baseline character-
istics were similar for patients
across the treatment groups, but
patients managed with active
surveillance were more likely to
have advanced-stage (Ann Arbor
stage III/IV) disease (38% vs. 22%;
p=0.09) and to be older (median
age = 47 vs. 39 years; p=0.03).
Of the nearly one-quarter
of patients who received active
surveillance, 28 (76%) never re-
quired treatment, and those who
did were mostly managed with
local radiotherapy or rituximab
monotherapy, with a median time
to first treatment of longer than
five years.
During a median follow-up
of 69 months (range = 4-512
months), the authors observed 40
PFS events, 13 PFS2 events, and
seven overall survival (OS) events.
This included 10 PFS events, one
PFS2 event, and no OS events
in the active surveillance group.
Thirty-seven of the 40 PFS events
were considered disease relapses
or progressions; the other three
patients died without experienc-
ing disease progression or relapse.
Overall, the five-year esti-
mates for PFS, PFS2, and OS were
85%, 97%, and 99%, respectively.
Survival outcomes were
excellent in all treatment groups,
and median PFS was not reached
in any group. Specifically, in
patients who received active
surveillance, 27% progressed
during follow-up, eight of whom
had NLPHL and two of whom
had transformed disease. Only
one patient experienced a second
relapse event.
“As could be expected, active
surveillance was associated with
a shorter PFS when compared
with any other treatment,” the
authors wrote, with five-year
PFS rates of 77% and 87%, re-
spectively (p=0.017). PFS2 was
similar between the groups,
with five-year PFS2 rates of
95% with active surveillance
and 97% with any other treatment
(p=0.71). No patient in the ac-
tive surveillance group died, while
five-year OS for any other treat-
ment group was 98% (p=0.38).
Looking at risk factors for PFS,
the authors found that bulky
disease ≥5 cm (hazard ratio [HR] =
3.0; 95% CI 1.3-7.0; p=0.01) and ex-
tranodal disease (HR=7.5; 95% CI
2.1-27.4; p=0.002) were associated
with shorter PFS. If patients who
initially received active surveillance
required additional treatment, the
addition of radiotherapy improved
PFS (HR=0.34; 95% CI 0.17-0.66;
p<0.001), particularly in those with
early-stage disease (HR=0.43; 95%
CI 0.19-0.97; p=0.035).
This was an exploratory analy-
sis, though, and “in keeping with
PERSPECTIVES
In this single-institution retrospective analysis, interestingly, patients who received active
surveillance as their primary management strategy had a remarkably favorable outcome.
Only 27% of these patients required treatment, and despite a lower PFS, there was no
difference in OS compared with patients receiving initial treatment. Notably, only two
patients managed with active surveillance experienced transformation and no patients
died because of lymphoma. These results support a “watch-and-wait” strategy in select
patients with NLPHL, similar to standard practice in patients with indolent NHL.
Given the retrospective nature of this study and the modest cohort size, criteria
for optimal patient selection for active surveillance cannot be determined. In addi-
tion, treatment allocation was individualized based on physician discretion and was
ASHClinicalNews.org
likely influenced by clinical characteristics that may be difficult to control for within
the context of multivariable analyses. Nonetheless, given the rarity of this entity,
observational data such as this must be relied on to guide clinical practice, and the
extremely favorable outcome seen in patients undergoing active surveillance provides
reassurance for the safety of this approach.
Laurie Sehn, MD, MPH
Medical Oncologist, BC Cancer Agency
Clinical Associate Professor, University of British Columbia
Vancouver, BC
ASH Clinical News
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