Phase 2, multicenter GIBB study of obinutuzumab plus bendamustine in previously untreated patients with chronic lymphocytic leukemia

Figures & data

Figure 1. GIBB study design for previously untreated patients with chronic lymphocytic leukemia receiving obinutuzumab/bendamustine (NCT02320487). BM: bone marrow; CLL: chronic lymphocytic leukemia; d: day; iwCLL: International Working Group guidelines for CLL; mo: month; MRD: minimal residual disease; PB: peripheral blood; y: year.

Table 1. Baseline patient demographics and disease characteristics in patients receiving obinutuzumab/bendamustine in the GIBB study (intent-to-treat population).

Characteristic	All patients (N = 102)
Median age, years (range)	61 (35–90)
Male/female, n (%)	70 (69)/32 (31)
ECOG PS, n (%)
0	54 (53)
1	45 (44)
2	3 (3)
Rai stage at screening, n (%)
0	6 (6)
I	19 (19)
II	32 (31)
III	11 (11)
IV	34 (33)
Binet stage at screening, n (%)
A	13 (13)
B	42 (41)
C	47 (46)
Median time from initial diagnosis to first dose of study treatment, y (range)	2.1 (0–15.8)
B symptoms present at screening, n (%)	37 (36)
FISH cytogenetics, n (%)^a
17p deletion	4 (4)
11q deletion	10 (10)
13q deletion	16 (16)
Trisomy 12	16 (16)
Normal	24 (24)
Missing/unknown	38 (37)
CD38, n (%)^b
High (≥30%)	39 (38)
Low (<30%)	62 (61)
ZAP-70 positive, n (%)^b	51 (50)
Elevated serum thymidine kinase level, n (%)^b	94 (92)
IgVH (n= 74), n (%)
Unmutated	49 (66)
Mutated	25 (34)
Elevated beta-2 microglobulin, n (%)^b	55 (54)

Data cutoff: 3 June 2019.

ECOG PS: Eastern Cooperative Oncology Group performance status; IgVH: immunoglobulin heavy variable chain; ZAP-70: zeta-chain-associated protein kinase 70.

^aCytogenetics abnormalities from whole blood samples at baseline were evaluated by fluorescence in situ hybridization (FISH). Patients may be counted in multiple categories; percentages may add up to more than 100%.

^bOne patient had unknown baseline CD38, ZAP-70, and serum thymidine kinase; 5 patients had unknown beta-2 microglobulin.

Figure 2. Time-to-event results for patients receiving obinutuzumab/bendamustine in the GIBB study for (A) duration of response, (B) progression-free survival, and (C) overall survival (modified intent-to-treat population). Data cutoff: 3 June 2019.

Table 2. Response at treatment completion in patients receiving obinutuzumab/bendamustine in the GIBB study (modified intent-to-treat population).

Response status^a, n (%)	All patients (N = 102)
Overall response rate, n (% [95% CI))	91 (89 [82–95])
Complete response	49 (48)
Complete response with  incomplete bone  marrow recovery	2 (2)
Partial response	38 (37)
Nodular partial response	2 (2)
Stable disease	4 (4)
Progressive disease	1 (1)
Not evaluable	6 (6)

Data cutoff: 3 June 2019.

^aResponse was measured using 2008 iwCLL guidelines [11].

Figure 3. Time to and duration of MRD negativity (<10⁻⁴) status in patients receiving obinutuzumab/bendamustine in the GIBB study in peripheral blood: (A) time to MRD negativity (<10⁻⁴) following initial positive MRD assessment and (B) duration of MRD-negativity defined as the time from first occurrence of MRD-negative status to subsequent MRD-positive status. Data cutoff: 3 June 2019.

Table 3. Treatment-emergent adverse events (TEAEs; ≥ 5% any grade) in patients receiving obinutuzumab/bendamustine in the GIBB study (safety population; N = 102).

n (%)	Any-Grade TEAEs	Grade ≥ 3 TEAEs
Any TEAE	102 (100)	71 (70)
Infusion-related reaction	72 (71)	9 (9)
Nausea	54 (53)	1 (1)
Pyrexia	37 (36)	1 (1)
Fatigue	36 (35)	4 (4)
Neutropenia^a	34 (33)	25 (25)
Rash	28 (27)	1 (1)
Constipation	27 (26)	0
Diarrhea	22 (22)	1 (1)
Vomiting	21 (21)	2 (2)
Thrombocytopenia	20 (20)	8 (8)
Insomnia	19 (19)	0
Headache	18 (18)	1 (1)
Peripheral edema	16 (16)	0
Cough	15 (15)	0
Dehydration	15 (15)	3 (3)
Anemia	14 (14)	8 (8)
Decreased neutrophil count	14 (14)	12 (12)
Upper respiratory tract infection	14 (14)	0
Arthralgia	13 (13)	0
Chills	13 (13)	0
Dizziness	12 (12)	1 (1)
Abdominal pain	11 (11)	1 (1)
Decreased appetite	11 (11)	1 (1)
Dry skin	10 (10)	0
Hypotension	10 (10)	2 (2)
Hypokalemia	9 (9)	2 (2)
Pain in extremity	9 (9)	0
Pneumonia	9 (9)	6 (6)
Bone pain	8 (8)	0
Decreased platelet count	8 (8)	5 (5)
Decreased weight	8 (8)	0
Dyspnea	8 (8)	0
Anxiety	7 (7)	0
Back pain	7 (7)	1 (1)
Dysgeusia	7 (7)	0
Dyspepsia	7 (7)	0
Flushing	7 (7)	0
Muscle spasms	7 (7)	0
Pruritus	7 (7)	0
Tumor lysis syndrome	7 (7)	6 (6)
Urinary tract infection	7 (7)	2 (2)
Bronchitis	6 (6)	0
Exertional dyspnea	6 (6)	0
Hypomagnesemia	6 (6)	0
Hyponatremia	6 (6)	3 (3)
Night sweats	6 (6)	0

Data cutoff: 3 June 2019.

^aIncluded 5 patients with grade 3/4 febrile neutropenia.

Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111(12):5446–5456.

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