Highlights
- •Ibrutinib (560 mg/day) showed a significant clinical activity in R/R primary central nervous system lymphoma and primary vitreoretinal lymphoma.
- •The intention-to-treat overall response rate was 52% after two 28-day cycles with activity in the brain, eyes and cerebrospinal fluid.
- •Responses were observed even in the absence of CD79B and MYD88 mutation.
- •The median progression-free survival was 4.8 months (95% confidence interval [CI]; 2.8–12.7).
- •Pulmonary aspergillosis occurred in 2 patients (4%). No fatal haemorrhage occurred.
Abstract
Background
Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell
lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs.
This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL
Patients and methods
This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R)
DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib
(560 mg/day) until disease progression or unacceptable toxicity occurred. The primary
outcome was the disease control (DC) rate after two months of treatment (P0 < 10%;
P1 > 30%).
Results
Fifty-two patients were recruited. Forty-four patients were evaluable for response.
After 2 months of treatment, the DC was 70% in evaluable patients and 62% in the intent-to-treat
analysis, including 10 complete responses (19%), 17 partial responses (33%) and 5
stable diseases (10%). With a median follow-up of 25.7 months (range, 0.7–30.5), the
median progression-free and overall survivals were 4.8 months (95% confidence interval
[CI]; 2.8–12.7) and 19.2 months (95% CI; 7.2-NR), respectively. Thirteen patients
received ibrutinib for more than 12 months. Two patients experienced pulmonary aspergillosis
with a favourable (n = 1) or fatal outcome (n = 1). Ibrutinib was detectable in the
cerebrospinal fluid (CSF). The clinical response to ibrutinib seemed independent of
the gene mutations in the BCR pathway.
Conclusion
Ibrutinib showed clinical activity in the brain, the CSF and the intraocular compartment and
was tolerated in R/R PCNSL. The addition of ibrutinib to standard methotrexate-base
induction chemotherapy will be further evaluated in the first-line treatment.
Clinical trial number
NCT02542514.
Keywords
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Article info
Publication history
Published online: July 03, 2019
Accepted:
May 28,
2019
Received in revised form:
May 23,
2019
Received:
April 10,
2019
Footnotes
☆The results of the interim analysis were presented as an oral presentation at the 58th annual meeting of the American Society of Hematology, San Diego, California, December 2016 (abstract #782), and part of the final analysis was presented as an oral presentation at the 14th International Conference on Malignant Lymphoma, Lugano, June 2017 (abstract # 60).
Identification
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