Role of lenalidomide in the treatment of peripheral T-cell non-Hodgkin lymphomas

Table 1 Clinical results of approved novel agents as monotherapy for relapsed/refractory T-cell lymphomas

Ref.	Patients, n	Study design	Treatment	Mechanism of action	Histology,	ORR	CR rate	Median PFS	Median DOR	Median OS
					(number of patients)
O’Connor et al[10], 2011	111	Multicenter phase II	Pralatrexate	Antifolate	Total evaluable (109)	29%	11%	3.5 mo	10.1 mo	14.5 mo
					PTCL-NOS (59)
					ALCL (17)	32%	NA
					AITL (13)	35%	NA
					MF (12)	8%	NA
					Other (8)	25%	NA
						38%	NA
Coiffier et al[11], 2014	130	Multicenter phase II	Romidepsin	Histone deacetylase inhibitor	Total evaluable	25%	15%	4 mo	28 mo	11.3 mo
					-130
					PTCL-NOS (69)	29%	14%
					ALCL ALK- (21)	24%	19%
					AITL (27)	30%	19%
					Other (13)	/	/
O’Connor et al[12], 2015	129	Multicenter phase II	Belinostat	Histone deacetylase inhibitor	Total evaluable	25.80%	10.80%	1.6 mo	13.6 mo	7.9 mo
					-120
					PTCL-NOS (77)	23%	NA
					ALCL ALK- (13)	15%	NA
					ALCL ALK+ (2)	/	NA
					AITL (22)	46%	NA
					Other (6)	16.60%	NA
Pro et al[13], 2017	58	Multicenter phase II	Brentuximab vedotin	Monoclonal antibody anti-CD30	ALCL	86%	57%	20 mo	25.6 mo	NR (estimated 5-yr OS 60%)
Kim et al[14], 2018	186	Multicenter, randomized, phase III	Mogamulizumab	Monoclonal antibody anti C-C chemokine receptor 4	MF or Sézary syndrome	28%	2.70%	7.7 mo	14.1 mo	NR

AITL: Angioimmunoblastic T-cell lymphoma; ALCL: Anaplastic T-cell lymphoma; ALK: Anaplastic lymphoma kinase; CR: Complete response; DOR: Duration of response; MF: Mycosis fungoides; NA: Not available; NR: Not reached; ORR: Overall response rate; OS: Overall survival; PFS: Progression-free survival; PTCL-NOS: Peripheral T-cell lymphomas: not otherwise specified.

Table 2 Clinical efficacy of lenalidomide single-agent in T-cell lymphomas

Ref.	Patient, n	Study design	Treatment	Histology (number of patients)	ORR	CR rate	Median PFS	Median DOR	Median OS
Ishida et al[44], 2016	26	Multicenter phase II	25 mg continuously until progression or unacceptable toxicity	ATLL (26)	42%	19%	3.8 mo	NR	20.3 mo
Querfeld et al[52], 2014	32	Multicenter phase II	25 mg for 21 d of a 28-d cycle; initial dose was reduced to 10 mg, with the possibility of increasing by 5 mg every cycle, until a maximum of 25 mg, until progression or up to 2 yr for SD or PR, while patients in CR received two additional cycles	Total evaluable (29)	28%	/	8 mo	10 mo	43 mo
				Mycosis fungoides (19)	36.8%
				Sézary syndrome (13)	15.4%
Zinzani et al[56], 2011	10	Phase II, bi-centric	25 mg for 21 d of a 28-d cycle for 4 cycles as induction phase; After the 4th cycle, patients who achieved at least a SD continued for other eight cycles as maintenance	PTCL-NOS (10)	30%	30%	NA	13 mo	NA
Morschhauser et al[51], 2013	54	Multicenter phase II	25 mg on d 1-21 of a 28-d cycle, until progression or unacceptable toxicity, for a maximum of 2 yr	Total evaluable (54)	22%	11%	2.5 mo (4.6 mo in AITL)	3.6 mo	NA
				AITL (26)	31%	15%
				PTCL-NOS (20)	20%	NA
				CTCL (3)	NA	NA
				ALCL (3)	NA	NA
				Cutaneous ALCL (1)	NA	NA
				Extranodal NK/T-cell, nasal type (1)	NA	NA
Toumishey et al[57], 2015	39	Multicenter phase II	25 mg daily on d 1-21 of a 28-d cycle, until progression or unacceptable toxicity	Total evaluable (39)	26%	7.7%	4 mo	13 mo	12 mo
				ALCL (10)	10%	/
				AITL (9)	33%	11.1%
				PTCL-NOS (14)	43%	14.3%
				Other (6)	/	/

AITL: Angioimmunoblastic T-cell lymphoma; ALCL: Anaplastic T-cell lymphoma; ATLL: Adult T-cell lymphoma/leukemia; CTCL: Cutaneous T-cell lymphoma; CR: Complete response; DOR: Duration of response; NA: Not available; NK: Natural killer; NR: Not reached; OS: Overall survival; PR: Partial response; ORR: Overall response rate; PFS: Progression-free survival; PTCL-NOS: Peripheral T-cell lymphomas: Not otherwise specified; SD: Stable disease.

Table 3 Toxicity profile of lenalidomide in clinical trials for T-cell lymphomas

Toxicity/Adverse event	Ishida et al[44]	Querfeld et al[52]	Morschhauser et al[51]	Toumishey et al[57]
Hematological toxicity
Anemia total	54%	41%	NR	26%
Anemia grade 3-4	19.2%	/	4%	11%
Leukopenia total	50%	22%	NR	NR
Leukopenia grade 3-4	38.5%	3%	4%	NR
Neutropenia total	73%	NR	NR	18%
Neutropenia grade 3-4	65.4%	NR	15%	16%
Thrombocytopenia total	77%	NR	NR	26%
Thrombocytopenia grade 3-4	23.1%	NR	20%	5%
Hypoalbuminemia	35%	28%	NR	NR
Grade 3-4	/	/	NR	NR
Constipation	31%	34%1	17%	44%
Grade 3-4	/	/	NR	3%
Nausea	23.1%	13%	NR	28%
Grade 3-4	3.8%	/	NR	/
Vomiting	23.1%	NR	NR	10%
Grade 3-4	/	NR	NR	/
Skin rash	23.1%	25%	NR	38%
Grade 3-4	7.6%	/	9%	11%
Fatigue	15.4%	59%	NR	56%
Grade 3-4	3.8%	22%	NR	11%
Diarrhea	NR	NR	NR	31%
Grade 3-4	NR	NR	NR	8%
Pain	NR	34%	NR	64%
Grade 3-4	NR	/	NR	21%
Infection	19.2%	34%	NR	26%
Grade 3-4	10.4%	9%	15%	5%
Neuropathy	NR	19%	NR	NR
Grade 3-4	NR	/	NR	NR
Lower leg edema	NR	47%	NR	28%
Grade 3-4	NR	/	NR	3%
Anorexia	NR	16%	NR	28%
Grade 3-4	NR	/	NR	5%
Respiratory disorders	10.4%	NR	NR	26%
Grade 3-4	7.6%	NR	13%	13%
Pulmonary embolism	NR	NR	NR	10%
Grade 3-4	NR	NR	NR	8%
Tumor flare reaction	NR	28%	14%	NR
Grade 3-4	NR	NR	4%	NR

¹Considered together with diarrhea; Gastrointestinal disorders. NR: Not reported.