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STANDARDS OF CARE
Cyclophosphamide, doxorubicin, vincristine, and prednisone
Combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is
currently considered the standard of care based on a large, randomized phase 3 study led by Fisher et al.
that explored the value of different intensified chemotherapy regimens compared to CHOP in patients with
intermediate- and high-grade NHL that included both B-cell and T-cell lymphomas . End points of the
[48]
study were overall response rate (ORR), time to treatment failure (TTF), disease-free survival (DFS), overall
survival (OS), and incidence of severe or life-threatening toxicity. This landmark trial showed no difference
in ORR, PFS, and DFS, but patients treated with CHOP developed fewer adverse events. At the time of the
study, there was no standardized differentiation between aggressive B-cell and T-cell lymphomas, and
CHOP chemotherapy has become the default standard of therapy for both subtypes for the past 30 years.
PTCL patients treated with doxorubicin-based chemotherapy have a 3-year PFS of 32% and overall survival
(OS) of 55% . Since then, there has been better characterization of lymphomas, e.g., diffuse large B-cell
[49]
lymphoma (DLBCL) and addition of anti-CD20 monoclonal antibody rituximab with improvement in
survival, but much less progress has been made for the T-cell lymphomas compared to the B-cell
counterpart.

Cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone
Adding more chemotherapy to the CHOP backbone has been studied as a means to improve outcomes. In a
secondary analysis of the German High-Grade NHL Study Group trials, the addition of etoposide to
standard CHOP chemotherapy has been shown to improve the 3-year event-free survival (EFS) to 75% from
51% with CHOP alone (P = 0.003) in patients younger than 60 with normal lactate dehydrogenase though
there was not a significant difference in OS . This finding is mostly because of treatment effect on patients
[50]
with ALK-positive ALCL, where treatment with Cyclophosphamide, doxorubicin, vincristine, etoposide,
and prednisone (CHOEP) was associated with a 3-year EFS of 91% compared to 57% when treated with
CHOP (P = 0.012); the effect was no longer significant in other subtypes of PTCL . An additional
[50]
retrospective study of Danish and Swedish patients with ALK-positive ALCL treated with CHOEP was
associated with better PFS (hazard ratio [HR] 0.48, P = 0.034) and OS (HR 0.34, P = 0.008) compared to
[51]
treatment with CHOP . In a meta-analysis performed in Asian patients, however, the addition of
etoposide did not improve response rates when compared to CHOP .
[52]
Infusional etoposide, doxorubicin, and vincristine with cyclophosphamide and prednisone
Given evidence of multidrug resistance by expression in relapsed and refractory lymphoma, prolonged
exposure to doxorubicin and vincristine over a 4-day infusion may overcome resistance mechanism
compared to the 1-day infusion used in CHOP . In the phase II study of dose-adjusted Infusional
[53]
etoposide, doxorubicin, and vincristine with cyclophosphamide and prednisone (EPOCH), 41 previously
untreated patients with PTCL (excluding ATLL) were treated, leading to an ORR of 78% (with 61%
achieving a complete response [CR]). The most common grade 3 or higher adverse events included
neutropenia (75%), anemia (41%), and thrombocytopenia (22%). After a median follow-up of 2 years, the
median PFS and OS were not reached. The 2-year PFS and OS were 53% and 73%, respectively. The decision
to choose CHOP, CHOEP, or EPOCH is usually dependent on the provider and/or institution.

Brentuximab vedotin plus CHP
Adding brentuximab vedotin (an antibody drug conjugate linking a monoclonal antibody against cluster of
differentiation 30 (CD30) and cytotoxic agent, monomethyl auristatin E [MMAE], Bv) to
cyclophosphamide, doxorubicin, and prednisone (Bv-CHP) compared to CHOP in the phase 3 frontline
ECHELON-2 trial met its primary endpoint and was the first regimen to get FDA approval in frontline
[6]
CD30-positive (defined as 10% of more expression by immunohistochemistry) PTCL . The median