NcXHF

NOVEL TREATMENTS FOR T-CELL LYMPHOMA
FIGURE 1. WHO 2008 Classification of Mature T-Cell Neoplasms According to Typical Presentation
mature T-cell and NK-cell neoplasms
nodal extranodal leukemic cutaneous
Peripheral T-cell lymphoma,
NOS
Angioimmunoblastic T-cell
lymphoma
Anaplastic large cell lymphoma,
ALK positive
Anaplastic large cell lymphoma,
ALK negative
Extranodal NK/T-cell lymphoma,
nasal type
Enteropathy-associated T-cell
lymphoma
Hepatosplenic T-cell lymphoma
Subcutaneous panniculitis-like T-
cell lymphoma ( subtype only)
T-cell prolymphocytic leukemia
T-cell large granular lymphocytic
leukemia
Aggressive NK-cell leukemia
Adult T-cell leukemia/lymphoma
Mycosis fungoides
Sézary syndrome
Primary cutaneous CD30-positive T-
cell lymphoproliferative disorders
Primary cutaneous anaplastic large cell
lymphoma
Lymphomatoid papulosis
Primary cutaneous peripheral T-cell
lymphomas, rare subtypes Primary
cutaneous gamma-delta T-cell
lymphoma
Primary cutaneous CD8 aggressive
epidermotropic T-cell lymphoma
Primary cutaneous CD4 small/medium
T-cell lymp homa
KEY POINTS
Outcomes for patients with peripheral T-cell lymphoma
treated with cyclophosphamide/doxorubicin/vincristine/
prednisone (CHOP)-like induction regimens with and without
front-line consolidative stem cell transplantation will be
summarized.
Clinical data supporting the regulatory approval of
pralatrexate, romidepsin, brentuximab vedotin, and
belinostat for patients with relapsed/refractory disease will
be reviewed.
Trials combining these novel agents in combination with
CHOP-like chemotherapy in previously untreated patients
will be outlined.
Studies using combinations of new agents in biologic
doublets as salvage regimens will be described.
Emerging clinical data on agents with promising clinical
efficacy in phase I studies will be highlighted.
and autologous stem cell transplantation (ASCT) in patients
who achieve a response has been explored. The ORR following
induction ranged from 66% to 82%, 41% to 72% of patients
received ASCT, and the median OS was 3 to 5
years. 6,10-14 Reimer et al treated 83 patients (32 with PTCL-
NOS) with CHOP induction followed by cyclophosphamidetotal
body irradiation conditioning and ASCT. At a median
follow-up of 33 months, the 3-year PFS and OS were 36% and
48% respectively. 13 The Nordic Lymphoma Group treated
160 patients with PTCL (excluding ALK ALCL) with biweekly
CHOP with etoposide (CHOEP-14). 11 At a median
follow-up of 60.5 months, the 5-year PFS and OS were 44%
and 51% respectively, with marginal improvement in PFS
(p 0.04) and OS (p 0.03) among patients with ALK
ALCL compared with other PTCL subtypes. In both studies,
patients who had transplants had markedly superior outcomes
compared with those who did not; however, the latter
group consisted mostly of patients whose disease did not respond
to induction therapy or had comorbidities precluding
SCT. The U.S. multicenter consortium reported that outside
of clinical trials, only 33/341 patients (10%) treated at large
academic centers received ASCT in fırst remission; this was
associated with improvement in both PFS (hazard ratio [HR]
0.48; 95% CI, 0.27 to 0.84, p 0.01) and OS (HR 0.48, 95% CI,
0.24 to 0.98, p 0.04), although the typical limitations of a
retrospective study apply. 7 Smith et al analyzed data collected
by the Center for International Blood and Bone Marrow
Transplant Research (CIBMTR) for 241 patients with mature
T-cell lymphomas who underwent transplantation. 15 Patients
in complete response (CR)1 had favorable outcomes
(3-year PFS and OS of 58% and 70% respectively), indicating
a major role for ASCT in patients with PTCL (other than
those with primary cutaneous or ALK ALCL) who are in
fırst remission. However, it should be noted that no prospective
randomized data demonstrating a clear advantage for
transplant over induction chemotherapy alone currently
exist.
Up-front allogeneic stem cell transplantation (alloSCT)
has been explored in a prospective phase II study in which
Corradini et al randomly assigned patients age 60 or older
whose disease responded to induction therapy to either
ASCT (14 patients) or alloSCT (23 patients) based on donor
availability. 10 The reported 4-year OS (92% vs. 69%, p 0.10)
and PFS (70% vs. 69%, p 0.92) were not signifıcantly different;
however, the study was neither designed nor powered
for this comparison. The CIBMTR multicenter retrospective
study attempted to compare outcomes for 115 patients who
received ASCT and 126 who received alloSCT; patients in the
alloSCT group were younger, but had more unfavorable features.
The 3-year PFS for ASCT versus alloSCT in this analysis
was 47% versus 33%, but only 17% of the patients who
received ASCT and 14% of those with alloSCT had received
just one prior line of treatment. 15 Thus, whether alloSCT as
front-line consolidation offers additional disease control
over ASCT remains controversial and is being addressed by
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