An update on the management of peripheral T-cell lymphoma and emerging treatment options

Figures & data

Table 1 Mature T- and NK-cell neoplasms: the World Health Organization (WHO) classification 2001 and 2008^1,2

	WHO classification 2001	WHO classification 2008
Leukemic	T-PLL	T-PLL
	T-LGLL	T-LGL
	Aggressive NK-cell leukemia	Chronic LPDs of NK-cells^b
	ATLL (HTLV-1+)	Aggressive NK-cell leukemia
		ATLL (HTLV-1+)
		Systemic EBV-positive T-cell LPDs of childhood^b
Nodal	AITL	AITL
	ALCL, systemic type	ALCL, ALK-positive
	PTCL-U	ALCL, ALK-negative^c
		PTCL-NOS
Extranodal	Extranodal NK-/T-cell lymphoma, nasal type	Extranodal NK-/T-cell lymphoma, nasal type
	Enteropathy-type T-cell lymphoma	Enteropathy-associated T-cell lymphoma
	Hepatosplenic γδ T-cell lymphoma	Hepatosplenic T-cell lymphoma
	Subcutaneous panniculitis-like T-cell lymphoma	Subcutaneous panniculitis-like T-cell lymphoma
Cutaneous	Mycosis fungoides	Mycosis fungoides
	Sézary syndrome	Sézary syndrome
	Primary cutaneous CD30+ T-cell LPD ALCL, cutaneous type Lymphomatoid papulosis^a Borderline lesions	Primary cutaneous CD30+ T-cell LPD Primary cutaneous aggressive epidermotropic CD8+ TCL^c Primary cutaneous small/medium CD4+ TCL^c Primary cutaneous γδ TCL^b
Uncertain	Blastic NK-cell lymphoma

Notes:

a Not considered a neoplastic disorder;

b new distinct entity;

c provisional entity.

Abbreviations: T-PLL, T-cell prolymphocytic leukemia; T-LGLL, T-cell large granular lymphocytic leukemia; T-LGL, T-cell large granular lymphocytic leukemia; ATLL, adult T-cell leukemia/lymphoma; HTLV-1, human T lymphotropic virus, type I; LPD, lymphoproliferative disorder; PTCL, peripheral T-cell lymphoma; PTCL-U, peripheral T-cell lymphoma, unspecified; PTCL-NOS, peripheral T-cell lymphoma, not otherwise specified; ALCL, anaplastic large-cell lymphoma; ALK, anaplastic lymphoma kinase.

Table 2 Major lymphoma subtypes by geographic region in the International T-cell lymphoma project⁶

PTCL subtype	Overall (%)	North America (%)	Europe (%)	Asia (%)
PTCL-NOS	25.9	34.4	34.3	22.4
AITL	18.5	16.0	28.7	17.9
ALCL, ALK+	6.6	16.0	6.4	3.2
ALCL, ALK–	5.5	7.8	9.4	2.6
NKTCL	10.4	5.1	4.3	22.4
ATLL	9.6	2.0	1.0	25
Enteropathy-type TCL	4.7	5.8	9.1	1.9
Hepatosplenic TCL	1.4	3.0	2.3	0.2
Primary Cutaneous ALCL	1.7	5.4	0.8	0.7
SCPTCL	0.9	1.3	0.5	1.3

Abbreviations: PTCL-NOS, peripheral T-cell lymphoma, not otherwise specified; AITL, angioimmunoblastic T-cell lymphoma; ALCL, anaplastic large-cell lymphoma; ALK, anaplastic kinase; NKTCL, natural killer T-cell lymphoma; ATLL, adult T-cell leukemia/lymphoma; TCL, T-cell lymphoma; SCPTCL, subcutaneous panniculitis-like T-cell lymphoma+; PTCL, peripheral T-cell lymphoma.

Note: Adapted from Vose J, Armitage J, Weisenburger D. International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26(25):4124–4130. Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.

Table 3 Selected studies of first-line therapies in PTCL

Study	Agent	Patient number (n)	ORR	Notable toxicities
Kim^Citation64	CHOEP + gemcitabine	26	77%	Grade 4 neutropenia (54%)
Sung^Citation63	CEOP-B	52	63.5%	Neutropenia
Gallamini^Citation66	Alemtuzumab + CHOP	24	75%	Grade 4 neutropenia and CMV reactivation
				Other major infections-JCV, pulmonary invasive aspergillosis, staph sepsis and pneumonia
Kim^Citation65	Alemtuzumab + CHOP	20	80%	90% grade 4 neutropenia 55% febrile neutropenia 25% CMV reactivation*
Simon^Citation62	VIP-rABVD vs CHOP 21	88 patients randomized	62%, no difference between two arms	Hematologic toxicity, transfusion requirement, and hospitalizations higher in VIP-rABVD arm
Takamatsu^Citation67	THP-COP	53	66%	Grade 3/4 cytopenias
Kluin-Nelemans^Citation68	Alemtuzumab + CHOP(intensified)	20	90%	Neutropenic fever, CMV reactivation/disease, EBV-related lymphoma

Note:

* Study closed due to adverse events.

Abbreviations: ORR, overall response rate; CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; CHOEP, cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide; CEOP-B, modified cyclophosphamide, epirubicin, vincristine, prednisone; VIP-rABVD, alternative therapeutic schedule including etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, dacarbazine; THP-COP, pirarubicin, cyclophosphamide, vincristine, prednisolone; CMV, cytomegalovirus; JC, John Cunningham virus; EBV, Epstein–Barr Virus; PTCL, peripheral T-cell lymphoma.

Table 4 Selected studies of novel therapies in relapsed or refractory PTCL

Study	Agent	Patients (n)	ORR
Mercieca^Citation92	Pentostatin	145	34%
Sallah^Citation93	Gemcitabine	10	60%
Enblad^Citation83	Alemtuzumab	14	35%
Arkenau^Citation94	Gemcitabine combination	16	69%
Dang^Citation86	Denileukin diftitox	27	48%
Bartlett^Citation84	Anti-CD30, iratumumab	24	17%
Kim^Citation95	Alemtuzumab + DHAP	24	50%
Zinzani^Citation76	Gemcitabine	20	55%
D’Amore^Citation87	Anti-CD4, zanolimumab	21	24%
Dueck^Citation90	Lenalidomide	24	30%
O’Connor^Citation74	Pralatrexate	115	29%
Piekarz^Citation81	Romidepsin	47	38%
Coiffier^Citation96	Romidepsin	131	30%

Abbreviations: DHAP, dexamethasone-cytarabine-cisplatin; PTCL, peripheral T-cell lymphoma.

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