Page 1533 - Hematology_ Basic Principles and Practice ( PDFDrive )

1360 Part VII Hematologic Malignancies

PFS and duration of response were 3.6 and 3.5 months, marked activity. It is likely that a systematic analysis of agents with
respectively. lineage-specific activity in PTCL will form the basis of novel, PTCL-
specific treatment platforms that will create future non-CHOP–based
Sorafenib opportunities for front-line care.
Sorafenib is a multikinase inhibitor that modulates multiple intracel-
lular pathways, including PDGFR/VEGFR and MAP kinase signal-
ing. One report evaluated sorafenib in 12 patients with T-cell CUTANEOUS T-CELL LYMPHOMAS
lymphomas (three with PTCL and nine with CTCL). While the
population was not that heavily treated (median number or prior This portion of the chapter focuses on the disorders that would be
treatments = 2), three achieved a CR and one underwent aSCT. The encompassed by the diagnosis cutaneous T-cell lymphoma (Table 85.4).
median EFS for the entire cohort was 3.5 months. At a median The most common subtypes of CTCLs are the epidermotropic vari-
follow-up of 11.2 months, 10 patients were alive (83%) and disease ants MF and the related leukemic variant, Sézary syndrome (SS).
stabilization or reduction was noted in 75% of patients.

Duvelisib Epidemiology
Duvelisib (IPI-145) is an oral inhibitor of PI3K-δ and -γ. Mutation
in PI3K has been found to be a recurring finding across all of cancer CTCLs account for 71% of the 3844 cutaneous lymphomas diag-
biology, as this pathway plays a critical role regulating many cellular nosed in the United States between 2001 and 2010. MF and SS are
processes including cell survival, proliferation, and differentiation. the most common CTCL subtypes worldwide, constituting 54% of
PI3K-δ and PI3K-γ isoforms are preferentially expressed in leukocytes
with distinct roles in T-cell function. A phase I trial of duvelisib was
performed which included 16 patients with PTCL. The median
number of prior therapies was four. Of the 31 patients evaluable, an TABLE Comparison of EORTC and WHO Classifications of
ORR of 42% was observed and in PTCL, the ORR was 47%, with 85.4 Primary Cutaneous Lymphoma
two CRs and five PRs. EORTC Classification WHO Classification
Plitidepsin Cutaneous T-Cell Lymphoma
Plitidepsin is a cyclic depsipeptide originally isolated from the tuni- Indolent clinical behavior Mycosis fungoides
cate Aplidium albicans and is commercially produced by chemical Mycosis fungoides variants Mycosis fungoides variants
synthesis. It displays a broad spectrum of anticancer activities, includ- Follicular mycosis fungoides Follicular mycosis fungoides
ing induction of apoptosis and G1/G2 cell cycle arrest. Plitidepsin
has demonstrated reproducible activity against a variety of malignant Pagetoid reticulosis Pagetoid reticulosis
+
cell lines, including leukemias and lymphomas. A phase II trial evalu- CTCL, large cell, CD30 + Primary cutaneous CD30 ALCL
+
ated plitidepsin in 67 patients, which included 34 patients with (CD30 lymphoproliferative
relapsed/refractory noncutaneous PTCL. Of the 29 evaluable patients disease, including
with noncutaneous PTCL, six patients demonstrated an objective lymphomatoid papulosis)
response to plitidepsin (two CRs and four PRs; ORR = 20.7%) with Lymphomatoid papulosis
a median PFS and duration of response of 1.6 and 2.2 months, Aggressive clinical behavior
respectively.
Sézary syndrome Sézary syndrome
CTCL, large cell, CD30 − Peripheral T-cell lymphoma,
FUTURE DIRECTIONS unspecified (most); extranodal
NK/T-cell lymphoma, nasal
Over the past several years there has been a remarkable increase in type
our understanding of the diversity within the PTCLs. The apprecia- Provisional Entities
tion that the mature T-cell lymphomas represent a vast spectrum of CTCL, pleomorphic, small/medium
both indolent and aggressive subtypes, commonly associated with sized
diverse clinical pictures with substantial global variation, has shaped
how we now classify and think about these diseases. Even prognosti- Subcutaneous panniculitis-like Subcutaneous panniculitis-like
cating the outcomes of patients with these diseases has become T-cell lymphoma T-cell lymphoma
remarkably complicated, because each subtype of PTCL is now Cutaneous B-Cell Lymphoma
widely recognized as possessing its own unique clinical behavior and Indolent clinical behavior Extranodal marginal zone B-cell
thus its own unique response to different therapeutic approaches. lymphoma
Eventually these prognostic models will be used to better risk-stratify Primary cutaneous immunocytoma
patients at diagnosis, allowing physicians to institute an optimal (marginal zone B-cell
treatment plan earlier, which may include ASCT for select patients lymphoma)
and aSCT for those with relapsed or refractory disease. Follicle center cell lymphoma (any
Unquestionably, however, the increase in the number of new drugs
available for the treatment of this group of diseases has begun to grade)
reshape our options when considering the management of patients Intermediate clinical behavior
with relapsed or refractory disease. As these new drugs are used with Primary cutaneous large B-cell
increasing frequency, each having significant single-agent activity in lymphoma of the leg
these traditionally chemotherapy-resistant diseases, the emergence of Provisional Entities
novel non-CHOP–based drug combinations will likely emerge. Primary cutaneous plasmacytoma Plasmacytoma
Perhaps most exciting is the recent demonstration that combinations
of these agents are associated with marked synergy in the preclinical Intravascular large B-cell Diffuse large B-cell lymphoma
setting, including combinations of drugs such as pralatrexate and lymphoma (intravascular)
romidepsin, hypomethylating agents and HDAC inhibitors, and ALCL, Anaplastic large-cell lymphoma; CTCL, cutaneous T-cell lymphoma;
aurora A kinase inhibitors, and romidepsin, many of which are being EORTC, European Organization for Research and Treatment of Cancer; NK,
natural killer; WHO, World Health Organization.
translated to the clinical setting with early promise of tolerability and