Efficacy and safety of single-agent pralatrexate for treatment of angioimmunoblastic T-cell lymphoma after failure of first line therapy: a pooled analysis

Figures & data

Table 1. Patient characteristics and efficacy.

	Maruyama et al., 2017	Hong et al., 2019	Combined
Study design	Open-label, non-randomized, multicenter, phase I/II clinical trial	Single-arm, open-label, multicenter, phase 3	N/A
Number of AITL patients	9	20	29
Males % (N)	44.4 (4/9)	50 (10/20)	48 (14/29)
Age Median (range)	71 (59–83)	59 (42–76)	62 (42–83)
Number of previous therapies Median (range)	2 (1–4)	2 (1–8)	2 (1–8)
Efficacy
CR% (N)	11.1 (1/9)	15 (3/20)	13.8 (4/29)
PR% (N)	33.3 (3/9)	40 (8/20)	37.9 (11/29)
SD% (N)	33.3 (3/9)	0	10.3 (3/29)
PD% (N)	22.2 (2/9)	30 (6/20)	27.6 (8/29)
NE% (N)	0	15 (3/20)	10.3 (3/29)
Time to response Median (range)	1.4 months (11–46 days)	1.4 months (39–244 days)	1.4 months (11–244 days)
Time on treatment Median (range)	1.6 months (12–285 days)	2.4 months (1–540 days)	1.87 months (1–540 days)
Duration of response Median (95% CI)	Not reached (4.6 months, not reached)	5.7 months (2.8, not reached)	6.4 months (3.3, not reached)
Progression-free survival, Median (95% CI)	5.6 months (1.4, not reached)	4.8 months (1.5, 7.9)	5.0 months (1.6, 7.9)
Overall survival, Median (95% CI)	Not reached (5.6, not reached)	18.0 months (8.9, not reached)	18.0 months (13.6, not reached)
Follow up time (censored patients) Median (range)	6.0 months (52–359 days)	17.6 months (84–614 days)	11.3 months (52–614 days)

Figure 1. Patient disposition for FOT12-CN-301 and PDX-JP1.

Figure 2. A pooled analysis showed an ORR of 52% (95% confidence interval: 0.34, 0.70) in a population of 29 patients with AITL. The size of each square in the forest plot is proportional to the weight assigned to each study in the model. The diamond symbolizes the aggregate ORR and 95% CI. The p-value from the Q-test was .62 and the I² was 0% (95% CI = 0 to 0%).

Figure 3. Kaplan–Meier analysis of duration of response (panel A, n = 15), progression-free survival (panel B, n = 29) and overall survival (C, n = 29).

Table 2. Safety (mucositis/oral mucositis/stomatitis and hematological toxicities as treatment-related adverse events of interest).

	Maruyama et al., 2017	Hong et al., 2019	Combined
Mucositis/stomatitis
Patients experiencing TRAE of interest, any grade, % (N)	66.7 (6/9)	85.0 (17/20)^a	79.3 (23/29)
Grade 1, % (N)	11.1 (1/9)	20.0 (4/20)	17.2 (5/29)
Grade 2, % (N)	22.2 (2/9)	30.0 (6/20)	27.6 (8/29)
Grade 3, % (N)	33.3 (3/9)	30.0 (6/20)	31.0 (9/29)
Grade 4, % (N)	0	0	0
Patients for whom TRAE of interest led to delay of treatment, % (N)	44.4 (4/9)	55 (11/20)	51.7 (15/29)
Patients for whom TRAE of interest led to dose reduction, % (N)	33.3 (3/9)	10 (2/20)	17.2 (5/29)
Patients for whom TRAE of interest led to discontinuation of treatment, % (N)	11.1 (1/9)	5 (1/20)	6.9 (2/29)
Hematological toxicities
Patients experiencing TRAE of interest, any grade, % (N)	88.9 (8/9)	90 (18/20)	89.7 (26/29)
Grade 1, % (N)	11.1 (1/9)	5.0 (1/20)	6.9 (2/29)
Grade 2, % (N)	11.1 (1/9)	25.0 (5/20)	20.7 (6/29)
Grade 3, % (N)	33.3 (3/9)	15.0 (3/20)	20.7 (6/29)
Grade 4, % (N)	33.3 (3/9)	40.0 (8/20)	37.9 (11/29)
Grade 5, % (N)	0	5.0 (1/20)	3.4 (1/29)
Patients for whom TRAE of interest led to delay of treatment, % (N)	55.6 (5/9)	45 (9/20)	48.3 (14/29)
Patients for whom TRAE of interest led to dose reduction, % (N)	0	5.0 (1/20)	3.4 (1/29)
Patients for whom TRAE of interest led to discontinuation of treatment, % (N)	11.1 (1/9)	10 (2/20; includes 1 death)	10.3 (3/29)

^aFor one of the Chinese patients who experienced oral mucositis/stomatitis, the grade of this TRAE was not available.

Table 3. Efficacy of single agent treatment options for r/r AITL. NA indicates that this data is not available for the subgroup of r/r AITL patients (may be only available for the r/r PTCL group as a whole).

Treatment	Number of R/R AITL patients	ORR	Median DoR	Median PFS	Median OS
Belinostat
O’Connor et al., 2015 [16]	22	46%	NA	NA	NA
Brentuximab vedotin
Horwitz et al., 2014 [6]	13	54%	5.5 months	6.7 months	NA
Chidamide
Shi et al., 2017 [17]	65	49%	NA	4.8 months (144.5 days)	NA
Shi et al., 2015 [18]	10	50%	NA	NA	NA
Forodesine
Maruyama et al., 2019 [19]	18	33%	NA	NA	NA
Mogamulizumab
Zinzani et al., 2016 [20]	12	17%	NA	NA	NA
Ogura et al., 2014 [21]	12	50%	NA	NA	NA
Pralatrexate
Zhu et al., 2020 (this analysis)	29	52%	6.4 months	5 months	18 months
O’Connor et al., 2018 [22]	13	8%	NA	NA	9.8 months
Romidepsin
Coiffier et al., 2014 [23]	27	30%	NA	NA	NA
Piekarz et al., 2011 [24]	6	17%	23 months	NA	NA

O'Connor OA, Horwitz S, Masszi T, et al. Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma: results of the pivotal phase II BELIEF (CLN-19) study. J Clin Oncol. 2015;33(23):2492–2499.

 PubMed Web of Science ®Google Scholar

Horwitz SM, Advani RH, Bartlett NL, et al. Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin. Blood. 2014;123(20):3095–3100.

 PubMed Web of Science ®Google Scholar

Shi Y, Jia B, Xu W, et al. Chidamide in relapsed or refractory peripheral T cell lymphoma: a multicenter real-world study in China. J Hematol Oncol. 2017;10(1):69.

 PubMedGoogle Scholar

Shi Y, Dong M, Hong X, et al. Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma. Ann Oncol. 2015;26(8):1766–1771.

 PubMed Web of Science ®Google Scholar

Maruyama D, Tsukasaki K, Uchida T, et al. Multicenter phase 1/2 study of forodesine in patients with relapsed peripheral T cell lymphoma. Ann Hematol. 2019;98(1):131–142.

 PubMed Web of Science ®Google Scholar

Zinzani PL, Karlin L, Radford J, et al. European phase II study of mogamulizumab, an anti-CCR4 monoclonal antibody, in relapsed/refractory peripheral T-cell lymphoma. Haematologica. 2016;101(10):e407–e410.

 PubMed Web of Science ®Google Scholar

Ogura M, Ishida T, Hatake K, et al. Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-CC chemokine receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma. J Clin Oncol. 2014;32(11):1157–1163.

 PubMed Web of Science ®Google Scholar

O’Connor O, Marchi E, Volinn W, et al. Strategy for assessing new drug value in orphan diseases: an international case match control analysis of the PROPEL study. JNCI Cancer Spectr. 2018;2(4):pky038.

 PubMed Web of Science ®Google Scholar

Coiffier B, Pro B, Prince HM, et al. Romidepsin for the treatment of relapsed/refractory peripheral T-cell lymphoma: pivotal study update demonstrates durable responses. J Hematol Oncol. 2014;7(1):11.

 PubMed Web of Science ®Google Scholar

Piekarz RL, Frye R, Prince HM, et al. Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood. 2011;117(22):5827–5834.

 PubMed Web of Science ®Google Scholar