Literature Scan
Can Risk-Adapted EPOCH-R Replace Intensive
Therapy for Burkitt Lymphoma?
A dose-adjusted regimen of etoposide, doxorubicin,
cyclophosphamide, vincristine, prednisone,
and rituximab (EPOCH-R, or R-EPOCH) led to high
rates of event-free and overall survival (EFS; OS)
in adults with treatment-naïve Burkitt lymphoma,
regardless of age or HIV status. However, patients
with cerebrospinal fluid (CSF) involvement by
lymphoma had a high risk for treatment failure
and toxicity-related death, suggesting that these
patients may require a different approach.
Mark Roschewski, MD, Clinical Director of
the Lymphoid Malignancies Branch of the National
Cancer Institute’s Center for Cancer Research and
coauthors published their findings in the Journal
of Clinical Oncology.
Adults with Burkitt lymphoma are typically
treated with dose-intensive combination chemotherapy
derived from pediatric leukemia regimens,
which the study investigators noted is
“acutely toxic with late sequelae.” With this
study, they hypothesized that risk-adapted,
dose-adjusted EPOCH-R could obviate the need
for highly dose-intensive chemotherapy, therefore
reducing toxicity.
The phase II trial enrolled 113 patients (median
age = 49 years; range = 18-86) with previously untreated
Burkitt lymphoma from across 22 centers.
Most participants (n=98; 87%) were considered to
have high-risk disease (defined as stage ≥3 disease,
an Eastern Cooperative Oncology Group performance
status score ≥2, or tumors measuring ≥7 cm).
Per study protocol, patients with low-risk disease
received 3 cycles of dose-adjusted EPOCH-R
without central nervous system (CNS) prophylaxis,
while patients with high-risk disease received 6
treatment cycles with intrathecal CNS prophylaxis.
High-risk patients who had leptomeningeal
involvement received extended intrathecal
treatment.
Of the patient population, 11 people (10%) had
CSF involvement and 28 (25%) were positive for
HIV.
The investigators reported efficacy results
for the 13 low-risk patients who received all 3
planned cycles and 80 high-risk patients who
TABLE. 4-Year Event-Free Survival
According to Prognostic Variables
Interim PET scan
4-Year Event-Free Survival, %
Negative 90.0
Positive 78.7
HIV status
Negative 84.5
Positive 84.9
Age group
18-39 years 81.1
40-59 years 87.5
≥60 years 85.4
received all 6 planned cycles. In the high-risk population,
5 patients died of adverse events early
in the treatment, including 3 patients with CSF
involvement.
At a median follow-up of 58.7 months,
the 4-year EFS rate for all 113 patients was
84.5%, while the 4-year OS rate was 87%.
The authors noted that all patients with
low-risk disease are in remission and the
EFS and OS rates in the high-risk population
were 82.1% and 84.9%, respectively.
“Relapses in the CNS after therapy
were uncommon,” they added, with only 2
relapses in the brain parenchyma among the
81 patients with high-risk disease who had no
pretreatment evidence of CSF involvement.
“Highly dose-intensive
chemotherapy is
unnecessary for cure,
and carefully defined
low-risk patients may be
treated with limited
chemotherapy.”
—Mark Roschewski, MD
As part of their analysis, the researchers
also explored variables associated with survival,
including interim PET scans in 14 low-risk and
85 high-risk patients. All scans were interpreted
as negative in the low-risk group, while 60% were
interpreted as negative in the high-risk group.
However, the 4-year EFS rate was not significantly
different between those high-risk patients with
a positive or negative interim PET scan (90% vs.
79%; p=0.12).
Similarly, HIV infection, age, and International
Prognostic Index score had no effect on survival.
CSF involvement was the only variable that was
strongly associated with survival, the authors concluded
(TABLE). In the group of 11 patients who had
CSF involvement at presentation, 6 experienced
disease progression or died.
As expected with the lower-intensity EPOCH-R
regimen used in this study, the authors reported
that the treatment was “tolerable” in this patient
population, across all age groups. While highly
dose-intensive regimens typically lead to serious
infections in 15 to 20% of patients during each
cycle of therapy, “serious infections were observed
in 6% of cycles in our study, despite the inclusion
of patients with HIV,” they wrote.
Other hematologic adverse events observed
across the 562 treatment cycles administered
during the study included grade 3/4 thrombocytopenia
(96 cycles; 17%) and febrile neutropenia (89
cycles; 16%). Nonhematologic toxicity included:
• tumor lysis syndrome: 5 patients (5%)
• grade 3/4 mucositis: 21 patients (19%)
• grade 3/4 sensory neuropathy: 5 patients (5%)
“Most serious complications occurred early in
therapy and were associated with impaired performance
status,” the researchers noted. However,
they added that, of 7 patients with ECOG scores of
3 or 4, 5 were alive without disease at last followup,
suggesting that impaired performance status
does not preclude successful treatment with doseadjusted
EPOCH-R.
“[Our results] suggest highly dose-intensive
chemotherapy is unnecessary for cure, and carefully
defined low-risk patients may be treated with
limited chemotherapy,” the authors wrote, adding
that the findings also support a strategy of riskadapted
intrathecal therapy (without the use of
high-dose methotrexate) to prevent CNS relapses.
The findings of the study are limited by
the nonrandomized design and the lack of a
head-to-head comparison between dose-adjusted
EPOCH-R and highly dose-intensive regimens.
The authors report no relevant conflicts of interest.
The study was sponsored by the National Cancer
Institute.
Reference
Roschewski M, Dunleavy K, Abramson JS, et al. Multicenter study of risk-adapted
therapy with dose-adjusted EPOCH-R in adults with untreated Burkitt lymphoma.
J Clin Oncol. 2020 May 26. [Epub ahead of print]
16 ASH Clinical News July 2020 Bonus Mid-Year Edition