Romidepsin is effective and well tolerated in older patients with peripheral T-cell lymphoma: analysis of two phase II trials

Figures & data

Table 1. Patient demographics and characteristics.

	Pivotal trial^a			NCI trial
	≥60 years old (n = 71)	<60 years old (n = 59)	p	≥60 years old (n = 23)	<60 years old (n = 24)	p
Age, median (range), years	67 (60–83)	50 (20–59)	NA	68 (61–84)	51 (27–59)	NA
Male, n (%)	49 (69)	39 (66)	.72	14 (61)	11 (46)	.39
ECOG performance status, n (%)^b			.02			.92
0	21 (30)	25 (42)		9 (39)	9 (38)
1	44 (62)	22 (37)		11 (48)	13 (54)
2	6 (9)	11 (19)		3 (13)	2 (8)
Missing	0	1 (2)		0	0
No. prior therapies, median (range)	2 (1–8)	2 (1–8)	.17	3 (1–7)	2 (1–6)	.27
Type of prior therapy, n (%)
Chemotherapy	70 (99)	59 (100)	1.00	23 (100)	24 (100)	NA
Monoclonal antibody therapy	8 (11)	12 (20)	.22	1 (4)	1 (4)	1.00
Other immunotherapy	6 (9)	8 (14)	.40	1 (4)	2 (8)	1.00
Other	3 (4)	1 (2)	–	1 (4)	3 (33)	–
Prior stem cell transplant, n (%)	7 (10)	14 (24)	.05	8 (35)	11 (46)	.56
Prior radiation therapy, n (%)	15 (21)	16 (27)	.54	11 (48)	8 (33)	.38
Duration of PTCL, median (range), years	1.3 (0.1–6.4)	1.3 (0.1–17.0)	.04	1.4 (0.4–15.1)	1.8 (0.2–17)	.70
PTCL subtype, n (%)^b			.02			.01
PTCL-NOS	40 (56)	29 (49)		13 (57)	14 (58)
AITL	19 (27)	8 (14)		5 (22)	2 (8)
ALK-negative ALCL	9 (13)	12 (20)		4 (17)	0
Other	3 (4)	10 (17)		1 (4)	8 (33)

ALCL: anaplastic large cell lymphoma; ALK: anaplastic lymphoma kinase; AITL: angioimmunoblastic T-cell lymphoma; ECOG: Eastern Cooperative Oncology Group; NA: not applicable; NCI: National Cancer Institute; NOS: not otherwise specified; PTCL: peripheral T-cell lymphoma.

a PTCL histologically confirmed by central pathology review. One patient <60 years old diagnosed with diffuse large B-cell lymphoma was excluded from the efficacy assessment.

b Percentages may not sum to 100 due to rounding.

Figure 1. Waterfall plots for best response in the (A) pivotal and (B) National Cancer Institute (NCI) trials. Blue bars represent younger patients and red bars represent older patients. For the pivotal trial, nodal responses are shown, while in the NCI trial, the composite responses including both nodal and non-nodal disease are shown. Hash marks indicate breaks in the y-axis. Patients with complete response have been normalized to −100%. It is evident that patients aged ≥60 can be found at both ends of the spectrum.

Table 2. Response rates.

	Pivotal trial^b			NCI trial^c
Best response category^a	≥60 years old (n = 71)	<60 years old (n = 59)	p	≥60 years old (n = 22)	<60 years old (n = 23)	p
ORR, n (%)	18 (25)	16 (27)	.82	7 (32)	10 (43)	.42
CR^d	10 (14)	10 (17)	.65	3 (14)	5 (22)	.47
PR	8 (11)	6 (10)	–	4 (18)	5 (22)	–
SD, n (%)	22 (31)	10 (17)	–	2 (9)	3 (13)	–
Time to response, median (range), days
Time to first response	56 (49–162)	56 (43–126)	.59	58 (48–135)	58 (45–345)	.65
Time to CR^d	109 (49–281)	104 (50–185)	1.00	56 (48–1246)	233 (56–345)	.65
Duration of response, median (range), months
All responders	NE (<1^e–56+)	NE (<1^e–46+)	.99^f	5 (3–55+)	12 (2–76+)	.55^f
Patients with CR^d	NE (<1^e–56+)	NE (2–46+)	1.00^f	NE (3–55+)	74 (9–76+)	.46^f

CR: complete response; NCI: National Cancer Institute; NE: not evaluable; ORR: objective response rate; PR: partial response; SD: stable disease.

a Response rates in the pivotal trial were assessed by independent review; response rates in the NCI trial were investigator assessed.

b PTCL histologically confirmed by central pathology review. One patient <60 years old diagnosed with diffuse large B-cell lymphoma was excluded from the efficacy assessment.

c One patient was discovered to be ineligible for enrollment after receiving first dose; one patient was reclassified as having diffuse large B-cell lymphoma.

d Includes patients with confirmed and unconfirmed CR in the pivotal trial.

e Patient elected to undergo stem cell transplant following the first response assessment of CR.

f Log-rank test.

Figure 2. Kinetic analysis for patients aged <60 and ≥60 years in the pivotal trial. Lymph node measurements obtained at baseline and restaging were summed at each time point and then equations were applied [20] to determine growth and regression rate constants (g and d, respectively). (A) A patient with first regression and then progression, where both g and d could be determined. (B) A patient in whom only d, regression rate, could be determined. (C) A patient in whom only g, growth rate, could be determined. (D) Data are summarized in this panel. (E) Calculated rates of d, tumor shrinkage, and g, growth, are shown in box plots. As shown, there was no statistical difference between the two age groups. IQR: interquartile range.

Table 3. Grade ≥3 adverse events.

	Pivotal trial		NCI trial^b
Adverse event^a n (%)	≥60 years old (n = 72)	<60 years old (n = 59)	≥60 years old (n = 23)	<60 years old (n = 24)
Thrombocytopenia	15 (21)	17 (29)	8 (35)	10 (42)
Neutropenia	13 (18)	13 (22)	12 (52)	10 (42)
Infections (all types pooled)	15 (21)	11 (19)	8 (35)	7 (29)
Anemia	6 (8)	8 (14)	4 (17)	9 (38)
Asthenia/fatigue	8 (11)	3 (5)	3 (13)	5 (21)
Leukopenia	4 (6)	4 (7)	11 (48)	11 (46)
Pyrexia	7 (10)	1 (2)	2 (9)	3 (13)
Vomiting	2 (3)	4 (7)	3 (13)	2 (8)

NCI: National Cancer Institute.

a Reported in ≥5% of patients in the pivotal trial.

b Reported all abnormalities as adverse events regardless of clinical significance.

Stein WD, Wilkerson J, Kim ST, et al. Analyzing the pivotal trial that compared sunitinib and IFN-alpha in renal cell carcinoma, using a method that assesses tumor regression and growth. Clin Cancer Res. 2012;18:2374–2381.

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