Lack of impact of type and extent of prior therapy on outcomes of mogamulizumab therapy in patients with cutaneous T cell lymphoma in the MAVORIC trial

Figures & data

Table 1. Classification of immediate prior systemic therapies in the MAVORIC trial for subgroup analyses.

Immunostimulatory (n = 33)	Immune-neutral (n = 55)	Immunoinhibitory (n = 49)			HDAC inhibitors (n = 13)
Interferon ○Interferon gamma-1β ○Interferon gamma Nivolumab ECP ECP + bexarotene ECP + peg-intron + topical steroids Interferon + bexarotene Lenalidomide	Retinoids ○Bexarotene ○Acitretin ○Isotretinoin ○Etretinate Brentuximab vedotin PUVA + low-dose bexarotene Oral bexarotene + NB-UVA Bucladesine sodium	Chemotherapy ○Doxorubicin ○Cladribine ○Gemcitabine ○ESHAP ○Sterile ifosfamide ○CHOP ○CVP ○Chlorambucil + prednisone ○TAC ○Procarbazine ○Cyclophosphamide ○Selinexor Methotrexate Pralatrexate Alemtuzumab	Oral steroids ○Prednisolone ○Triamcinolone topical ○Oral prednisolone ○Prednisone 20 mg ○Fludrocortisone ○Prednisone ○Prednisolone 5 mg MLN9708 (ixazomib) Forodesine hydrochloride Hydroxychloroquine Romidepsin + lenalidomide	Romidepsin Quisinostat Belinostat Vorinostat

CHOP: cyclophosphamide, doxorubicin, vincristine, prednisone; CVP: cyclophosphamide, vincristine, prednisone; ECP: extracorporeal photopheresis; ESHAP: etoposide, methylprednisolone, high-dose cytarabine, cisplatin; HDAC: histone deacetylase; NB-UVA: narrowband ultraviolet A; PUVA: psoralen plus ultraviolet A; TAC: Taxotere, Adriamycin, cyclophosphamide.

Table 2. Baseline disease stage and median PFS, confirmed ORR, and median DOR after mogamulizumab treatment by number of prior systemic therapies in patients randomized to mogamulizumab (ITT population).

	Baseline			After mogamulizumab treatment
Number of prior CTCL therapies	Stage IB/II	Stage III/IV	Total	ORR, % (95% CI)		Median PFS, months
	n (%)	n (%)	n (%)					Median DOR, months
	(n = 68)	(n = 118)	(N = 186)					(95% CI)
				n		n		n
0	0	0	0	0	–	0	–	0	–
1	12 (17.6)	16 (13.6)	28 (15.1)	28	25.0 (10.7, 44.9)	28	5.67	28	13.1 (3.8, 13.1)
2	13 (19.1)	27 (22.9)	40 (21.5)	40	17.5 (7.3, 32.8)	40	9.37	40	19.9 (6.1, 20.6)
3	17 (25.0)	23 (19.5)	40 (21.5)	40	35.0 (20.6, 51.7)	40	9.00	40	18.0 (4.7, 18.0)
4	3 (4.4)	19 (16.1)	22 (11.8)	9	40.9 (20.7, 63.6)	22	10.30	22	19.2 (3.8, –)
5	4 (5.9)	8 (6.8)	12 (6.5)	12	16.7 (2.1, 48.4)	12	5.77	12	14.0 (–, –)
≥6	19 (27.9)	25 (21.2)	44 (23.7)	44	29.5 (16.8, 45.2)	44	8.43	44	9.4 (4.5, –)
Median	3.0	3.0	3.0
Minimum	1	1	1
Maximum	18	15	18

CI: confidence interval; CTCL: cutaneous T-cell lymphoma; DOR: duration of response; ORR: overall global response rate; PFS: progression-free survival.

Figure 1. (A) Confirmed global ORR, (B) median PFS, and (C) DOR to mogamulizumab by immediate prior systemic therapy and prior HDAC inhibitor exposure (ITT population). CR: complete response; DOR: duration of response; ECP: extracorporeal photopheresis; HDAC: histone deacetylase; ORR: overall global response rate; PFS: progression-free survival; PR: partial response.

Table 3. Baseline characteristics and outcomes by immediate prior therapy class in patients randomized to mogamulizumab (ITT population).

Variable	Immunostimulatory (n = 33)	Immune-neutral (n = 55)	Immunoinhibitory (n = 49)	HDAC inhibitors (n = 13)
Baseline
Age at screening, years, mean (SD)	64.6 (12.7)	59.0 (13.7)	63.8 (14.4)	67.3 (10.1)
Age ≥ 65 years, n (%)	18 (55)	22 (40)	22 (45)	7 (54)
Male gender, n (%)	23 (70)	26 (47)	29 (59)	6 (46)
ECOG performance status, n (%)
0	22 (67)	36 (65)	24 (49)	4 (31)
1	11 (33)	19 (35)	24 (49)	9 (69)
2	0	0	1 (2)	0
After mogamulizumab treatment
ORR, %	21.2	36.4	20.4	38.5
PFS, months, median (95% CI)	10.3	8.4	10.3	5.1
	(4.67, 19.03)	(5.67, 20.13)	(4.7, 15.03)	(1.03, NE)
DOR, months, median (95% CI)	18.0	14.0	8.5	NE
	(5.60, 20.57)	(12.20, 19.23)	(3.77, NE)	(4.47, NE)

CI: confidence interval; DOR: duration of response; ECOG: Eastern Cooperative Oncology Group; HDAC: histone deacetylase; NE: not estimable; ORR: overall global response rate; PFS: progression-free survival; SD: standard deviation.

Table 4. Effect of immune activity of immediate prior systemic therapy on PFS and confirmed ORR with mogamulizumab.

Parameter	Comparison against immune-neutral group	Parameter estimate	Standard error	χ^2	p value
Confirmed ORR^a
Immune category	Stimulatory	−0.7512	0.4296	3.0579	0.0803
	Inhibitory	−0.7322	0.3538	4.2831	0.0385
	HDACi	0.7578	0.6488	1.3644	0.2428
Time*Immune category	Stimulatory	0.0073	0.0058	1.5748	0.2095
	Inhibitory	0.0053	0.0041	1.6808	0.1948
	HDACi	−0.0116	0.0104	1.2394	0.2656
PFS^b
Immune category	Stimulatory	−0.3453	0.4853	0.5063	0.4767
	Inhibitory	0.0058	0.4141	0.0002	0.9888
	HDACi	−0.3448	0.7346	0.2203	0.6388
Time*Immune category	Stimulatory	0.0079	0.0067	1.4004	0.2367
	Inhibitory	0.0002	0.0057	0.0013	0.9711
	HDACi	0.0142	0.0082	2.9674	0.085

HDACi: histone deacetylase inhibitor; ORR: overall global response rate; PFS: progression-free survival.

^aLogistic regression model.

^bCox proportional hazards model. For both models, disease type, disease stage, region (United States, Japan, and Rest of World), time of immediate prior therapy to first treatment with mogamulizumab, immune category, and interaction term between time of immediate prior therapy and immune category were used as covariates based on data from eligible subjects in the mogamulizumab treatment group (n = 150).