Efficacy and safety of ibrutinib in diffuse large B-cell lymphoma: A single-arm meta-analysis

Hou, Kelu; Yu, Zhiying; Jia, Yueping; Fang, Huihui; Shao, Shuai; Huang, Lin; Feng, Yufei

doi:10.1016/j.critrevonc.2020.103010

Cited by 37 publications

(33 citation statements)

References 72 publications

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“…Although the combination of ibrutinib and radiotherapy also shows a very high remission rate, both OR and CR were 85%, in fact only two studies have reported the efficacy of ibrutinib combined with radiotherapy, and the number of cases is small, so its exact effect requires further studies by expanding the sample size. In addition, the meta-analysis by Hou et al reported that the OR and CR rates for ibrutinib in the treatment of DLBCL were 57.9 and 35%, respectively ( 9 ). Among these, the OR and CR of ibrutinib monotherapy were 41.6 and 15.2%, respectively, and the OR and CR of ibrutinib combined with the rituximab-based chemotherapy were 72 and 47.5%, respectively ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the meta-analysis by Hou et al reported that the OR and CR rates for ibrutinib in the treatment of DLBCL were 57.9 and 35%, respectively ( 9 ). Among these, the OR and CR of ibrutinib monotherapy were 41.6 and 15.2%, respectively, and the OR and CR of ibrutinib combined with the rituximab-based chemotherapy were 72 and 47.5%, respectively ( 9 ). Our systematic analysis of PCNSL showed that the remission rate of ibrutinib for the treatment of PCNSL was higher than that of systemic DLBCL.…”

Section: Discussionmentioning

confidence: 99%

“…Prospective non-randomized studies (single-arm studies) were assessed by methodological index for non-randomized studies (MINORS) ( 8 ). The retrospective studies without a comparison group were assessed by JBI Critical Appraisal Checklist for Case Series ( 9 ).…”

Section: Methodsmentioning

confidence: 99%

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Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis

Sun

et al. 2021

Front. Oncol.

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BackgroundCentral nervous system lymphoma (CNSL) is an aggressive lymphoma. Studies investigating primary CNSL determined that the Bruton tyrosine kinase (BTK) played an important role in pathogenesis. Ibrutinib, an oral BTK inhibitor, is a new treatment strategy for CNSL. The purpose of this meta-analysis was to clarify the effectiveness and safety of ibrutinib in the treatment of CNSL.MethodsA systematic search of PubMed, Embase, Cochrane library, Wanfang Data Knowledge Service Platform, and China National Knowledge Infrastructure databases was conducted through to 31 October 2019. Studies involving patients with CNSL who received ibrutinib that reported the overall response (OR), complete remission (CR), and partial response (PR) were included. The random-effects or fixed-effects model with double arcsine transformation was used for the pooled rates and 95% confidence intervals (CI) were determined for all outcomes.ResultsEight studies including 162 patients were identified and included in the meta-analysis. The pooled OR rate after treatment with ibrutinib was 69% (95% CI, 61–79%, I2 = 47.57%, p = 0.06), while the pooled CR and PR was 52% (95% CI, 35–68%, I2 = 74.95%, p = 0.00) and 17% (95% CI, 7–30%, I2 = 67.85%, p = 0.00), respectively. Among PCNSL patients, including new diagnoses PCNSL and R/R PCNSL, the pooled OR rate was 72% (95% CI, 63–80%, I2 = 49.20%, p = 0.06) while the pooled CR and PR rates were 53% (95% CI, 33–73%, I2 = 75.04%, p = 0.00) and 22% (95% CI, 14–30%, I2 = 46.30%, p = 0.07), respectively. Common adverse events above grade 3 included cytopenia and infections.ConclusionsThe ibrutinib-containing therapy was well tolerated and offered incremental benefit to patients with CNSL. However, randomized-controlled studies that directly compare efficacy and adverse events of ibrutinib are still needed.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42020218974.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis

Sun

et al. 2021

Front. Oncol.

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“…Among them, the combination of bendamustine‐rituximab (BR), mainly as 2nd‐line treatment, induced responses of 46%–63% in three retrospective studies, retaining a favorable toxicity profile 17–19 . Novel agents including checkpoint inhibitors, bispecific antibodies and others, may be effective in subsets of patients 20–29 . Allogeneic stem cell transplantation (alloSCT) use is limited to a minority of highly selected, transplant‐eligible patients with available donors, who present chemosensitive relapse after ASCT 30 .…”

Section: Introductionmentioning

confidence: 99%

Real‐life experience with the combination of polatuzumab vedotin, rituximab, and bendamustine in aggressive B‐cell lymphomas

Dimou

Papageorgiou

Stavroyianni

et al. 2021

Hematological Oncology

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Transplant‐ineligible relapsed/refractory (rr) diffuse large B‐cell lymphoma (DLBCL) patients represent an unmet medical need. Polatuzumab vedotin (Pola), an anti‐CD79b antibody‐drug‐conjugate (ADG), with bendamustine‐ rituximab(BR) has recently gained approval for these patients, both in the USA and Europe, based on the GO29365 phase IIb trial. Real‐life data with Pola are extremely limited. We report the outcomes of 61 Greek patients, who received Pola‐(B)R mainly within a compassionate use program. Treatment was given for up to six 21‐day cycles. Bendamustine was omitted in three cases due to previous short‐lived responses. Fourty‐nine rrDLBCL(efficacy cohort‐EC) and 58 rr aggressive B‐NHL (safety cohort‐SC) patients received at least 1 Pola‐BR cycle. Twenty‐one (43%) patients of the EC responded with 12/49 (25%) CR and 9/49 (18%) PR as best response. Median progression–free survival, overall survival and duration of response were 4.0, 8.5, and 8.5 months respectively, while 55% of patients experienced a grade ≥3 adverse event, mainly hematologic. Treatment discontinuations and death during treatment were mainly due to disease progression. Twenty‐two (41%) patients received further treatment; 11/22 are still alive, including one after CAR‐T cells, and two after stem cell transplantation. Our data confirm that Pola‐BR is a promising treatment for rrDLBCL patients, inducing an adequate response rate with acceptable toxicity. Pola‐BR could be used as bridging therapy before further consolidative treatments.

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“…The Btk inhibitor ibrutinib is FDA approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, MZ lymphoma, and Waldenström's macroglobulinemia (19)(20)(21). Ibrutinib has also shown promise in several clinical trials for other types of B-cell malignancies, including diffuse large BCL (22). However, the response to ibrutinib is variable and several different mechanisms of ibrutinib resistance have been described (23).…”

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confidence: 99%

TNF receptor-associated factor 3 restrains B-cell receptor signaling in normal and malignant B cells

Whillock

Ybarra

Bishop

2021

Journal of Biological Chemistry

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TRAF3 has diverse signaling functions, which vary by cell type. Uniquely in B lymphocytes, TRAF3 inhibits homeostatic survival. Highlighting the role of TRAF3 as a tumor suppressor, loss-of-function TRAF3 mutations are associated with human B-cell malignancies, while B-cell-specific deletion of TRAF3 in mice leads to autoimmunity and lymphoma development. The role of TRAF3 in inhibiting noncanonical NF-κB activation, CD40 and BAFF-R signaling to B cells is well documented. In contrast, TRAF3 enhances many T-cell effector functions, through associating with and enhancing signaling by the T-cell receptor (TCR)-CD28 complex. The present study was designed to determine the role of TRAF3 in signaling via the B-cell antigen receptor (BCR). The BCR is crucial for antigen recognition, survival, proliferation, and antibody production, and defects in BCR signaling can promote abnormal survival of malignant B cells. Here, we show that TRAF3 is associated with both CD79B and the BCR-activated kinases Syk and Btk following BCR stimulation. BCR-induced phosphorylation of Syk and additional downstream kinases was increased in TRAF3 −/− B cells, with regulation observed in both follicular and marginal zone B-cell subsets. BCR stimulation of TRAF3 −/− B cells resulted in increased surface expression of MHC-II, CD80, and CD86 molecules. Interestingly, increased survival of TRAF3 −/− primary B cells was resistant to inhibition of Btk, while TRAF3-deficient malignant B-cell lines showed enhanced sensitivity. TRAF3 serves to restrain normal and malignant BCR signaling, with important implications for its role in normal B-cell biology and abnormal survival of malignant B cells.

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Efficacy and safety of ibrutinib in diffuse large B-cell lymphoma: A single-arm meta-analysis

Cited by 37 publications

References 72 publications

Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis

Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis

Real‐life experience with the combination of polatuzumab vedotin, rituximab, and bendamustine in aggressive B‐cell lymphomas

TNF receptor-associated factor 3 restrains B-cell receptor signaling in normal and malignant B cells

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