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Treating classical Hodgkin lymphoma: Spotlight on targeted therapies
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Bruton kinase inhibitors such as ibrutinib have significantly improved the treatment landscape of chronic lymphocytic leukemia (CLL). Ibrutinib and venetoclax, a B-cell lymphoma 2 inhibitor, are complementary in their mode of action; phase II studies have shown deep, durable responses, and improvements in progression-free survival (PFS), including in patients with high-risk CLL disease.
The Lymphoma Hub has previously reported findings from the GLOW trial. Here, we summarize a recently published article by Niemann et al.1 in The Lancet Oncology on the 4-year follow-up of the phase III GLOW trial (NCT03462719) investigating fixed duration ibrutinib + venetoclax vs chlorambucil + obinutuzumab in patients with previously untreated CLL.
GLOW is a randomized, multicenter study conducted across 14 countries in patients with previously untreated CLL. Eligible patients were aged ≥65 years or 18–64 years with comorbidities (cumulative illness rating scale score of >6/creatinine clearance of <70 mL/min), or both and had an Eastern Cooperative Oncology Group performance status of ≤2. Patients were randomized as shown in Figure 1.
The primary endpoint was PFS assessed by an independent review committee, defined as the time from randomization until disease progression or death from any cause.
Secondary endpoints included:
Figure 1. Treatment schema*
OD, once daily.
*Adapted from Niemann, et al.1
A total of 211 patients received ibrutinib + venetoclax (n = 106) and chlorambucil + obinutuzumab (n = 105). The baseline characteristics are summarized in Table 1.
Table 1. Baseline characteristics*
Characteristic, % (unless otherwise stated) |
Ibrutinib + venetoclax arm |
Chlorambucil + |
|
Median age, years |
71 |
71 |
|
Sex |
|
|
|
Male |
55.7 |
60.0 |
|
ECOG PS 1−2 |
67.0 |
62.9 |
|
Median CIRS score, n |
9 |
8 |
|
>6† |
69.8 |
58.1 |
|
Median CrCL, mL/min |
66.5 |
63.2 |
|
Rai stage III–IV |
57.3 |
52.5 |
|
Bulky disease ≥5 cm |
39.0 |
36.2 |
|
Elevated LDH† |
33.0 |
48.6 |
|
IGHV status‡ |
|
|
|
Mutated |
30.2 |
33.3 |
|
Unmutated |
63.2 |
54.3 |
|
Unknown |
6.6 |
12.4 |
|
Del(11q) |
18.9 |
17.1 |
|
TP53 mutation |
6.6 |
1.9 |
|
CIRS, cumulative illness rating scale; CrCL, creatinine clearance; ECOG PS, Eastern Cooperative Oncology Group performance status; IGHV, immunoglobulin heavy chain variable region gene; IQR, interquartile range; LDH, lactate dehydrogenase. |
At a median follow-up of 46 months:
Figure 2. 42-month PFS in ibrutinib + venetoclax arm vs chlorambucil + obinutuzumab arm*
PFS, progression-free survival.
*Adapted from Niemann et al.1
The 4-year follow-up data of the GLOW trial demonstrated that fixed-duration ibrutinib + venetoclax continues to significantly improve PFS and achieve an OS advantage compared with chlorambucil + obinutuzumab in patients with previously untreated CLL. The findings support the clinical use of this combination regimen as a first-line treatment option in patients with CLL.
Supported by an educational grant from Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC. All content is developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource.
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