Phase 1 study of inotuzumab ozogamicin combined with R-GDP for the treatment of patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma

Figures & data

Table 1. Patient characteristics.

Characteristics	Patients (n = 55)
Median age (range), years	65 (25–81)
Men, n (%)	37 (67)
Race, n (%)
White	35 (64)
Asian	16 (29)
Black/African American	2 (4)
Other	2 (4)
Histologic subtype,^a n (%)
DLBCL	21 (38)
FL^b	14 (25)
MCL	13 (24)
SLL	3 (5)
MZL	1 (2)
Other indolent B-cell NHL^c	3 (5)
ECOG performance status, n (%)
0	23 (42)
1	28 (51)
2	4 (7)
IPI score (excluding FL), n (%)
0	3 (5)
1	10 (18)
2	14 (25)
3	9 (16)
4	4 (7)
5	1 (2)
FLIPI score for FL, n (%)
0	0
1	1 (2)
2	4 (7)
3	6 (11)
4	3 (5)
5	0
Stage III/IV disease, n (%)	41 (75)
No. of prior antilymphoma regimens, n (%)
1	11 (20)
2	20 (36)
3	15 (27)
≥4	9 (16)
Median no. of prior antilymphoma regimens (range)	2 (1–6)
Prior radiotherapy, n (%)	15 (27)
Refractory^d to most recent prior anticancer treatment, n (%)	23 (42)

DLBCL: diffuse large B-cell lymphoma; ECOG: Eastern Cooperative Oncology Group; FL: follicular lymphoma; FLIPI: Follicular Lymphoma International Prognostic Index; IPI: International Prognostic Index; MCL: mantle cell lymphoma; MZL: marginal zone lymphoma; NHL: non-Hodgkin lymphoma; SLL: small lymphocytic lymphoma.

^a Disease stage at screening (stage 1A, n = 5; stage 2 A/B, n = 9; stage 3 A/B, n = 17; stage 4 A/B, n = 24).

^b FL stage at screening (stage 1A, n = 1; stage 2A, n = 1; stage 3A/B, n = 7; stage 4 A/B, n = 5).

^c Other indolent B-cell NHL includes lymphoplasmacytic lymphoma, Waldenstrom’s macroglobulinemia, and low-grade B-cell lymphoma favoring FL.

^d Best response of stable or progressive disease during most recent prior anticancer therapy.

Table 2. Treatment-related AEs.^a

AE, n (%)	Patients receiving RP2D in parts 1–3 (n = 36)		Total (n = 55)
	All grades	Grade ≥3	All grades	Grade ≥3
Thrombocytopenia	30 (83)	26 (72)	47 (85)	41 (75)
Neutropenia	22 (61)	21 (58)	38(69)	34 (62)
Anemia	12 (33)	5 (14)	21 (38)	10 (18)
Fatigue	14 (39)	2 (6)	20 (36)	4 (7)
Nausea	13 (36)	1 (3)	18 (33)	1 (2)
Lymphopenia	7 (19)	4 (11)	16 (29)	12 (22)
Leukopenia	7 (19)	6 (17)	14 (25)	13 (24)
Constipation	6 (17)	0	12 (22)	0
Vomiting	8 (22)	1 (3)	10 (18)	1 (2)
AST increased	3 (8)	0	9 (16)	0
Decreased appetite	7 (19)	1 (3)	9 (16)	1 (2)
Pyrexia	4 (11)	0	7 (13)	0
Febrile neutropenia	6 (17)	6 (17)	7 (13)	7 (13)

AE: adverse event; AST: aspartate aminotransferase; RP2D: recommended phase 2 dose.

^a Treatment-related AEs occurring on or after the first dose date until 56 days after the last dose in ≥10% of patients treated at the RP2D or in total are shown.

Table 3. Antitumor activity.

	Indolent^a (n = 21)	Aggressive^b (n = 34)	Patients receiving RP2D in Part 1–3 (n = 36)	Total (n = 55)
Response, n (%)
ORR	14 (67)	15 (44)	18 (50)	29 (53)
Best response
CR	4 (19)	7 (21)	5 (14)	11 (20)
PR	10 (48)	8 (24)	13 (36)	18 (33)
SD	4 (19)	10 (29)	10 (28)	14 (25)
PD	2 (10)	6 (18)	5 (14)	8 (15)
Not assessed^c	1 (5)	3 (9)	3 (8)	4 (7)
PFS^d
Number of events	11	24	25	35
Censored patients, n	10	10	11	20
Probabilities of PFS,^e (95% CI)
6 months	0.71 (0.44 − 0.87)	0.50 (0.31 − 0.67)	0.54 (0.35 − 0.70)	0.58 (0.43 − 0.71)
12 months	0.52 (0.26 − 0.73)	0.29 (0.14 − 0.46)	0.29 (0.14 − 0.46)	0.37 (0.23 − 0.51)
24 months	0.32 (0.12 − 0.55)	0.20 (0.07 − 0.37)	0.14 (0.03 − 0.32)	0.24 (0.12 − 0.38)
OS^f
Number of events	7	16	15	23
Censored patients, n	14	18	21	32
Probabilities of OS,^e (95% CI)
6 months	0.80 (0.55 − 0.92)	0.81 (0.63 − 0.91)	0.82 (0.64 − 0.92)	0.81 (0.67 − 0.89)
12 months	0.75 (0.50 − 0.89)	0.53 (0.35 − 0.69)	0.57 (0.38 − 0.72)	0.61 (0.47 − 0.73)
24 months	0.63 (0.38 − 0.81)	0.49 (0.31 − 0.65)	0.53 (0.34 − 0.69)	0.55 (0.40 − 0.67)

CI: confidence interval; DOR: duration of response; OS: overall survival; PFS: progression-free survival; CR: complete response; ORR: overall (objective) response rate (CR + PR); PD: progressive disease; PR: partial response; SD: stable disease.

^a Indolent non-Hodgkin lymphoma includes follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, lymphoplasmacytic lymphoma, Waldenstrom’s macroglobulinemia, and low-grade B-cell lymphoma favoring follicular lymphoma.

^b Aggressive non-Hodgkin lymphoma includes diffuse large B-cell lymphoma and mantle cell lymphoma.

^c Includes three patients with aggressive lymphoma and 1 with indolent lymphoma who did not have any post-baseline disease assessment and hence no best overall response reported.

^d Patients without an event (PD [including symptomatic deterioration], new anti-lymphoma therapy, or death) were censored at the date of the last valid post baseline tumor assessment. Patients without a PFS event and without a post baseline tumor assessment were censored at the date of first dose.

^e Kaplan–Meier’s estimated probabilities.

^f Patients were censored if they were alive at the date of last contact.