Single-agent ibrutinib in relapsed or refractory follicular lymphoma: a phase 2 consortium trial

Bartlett, Nancy L.; Costello, Brian A.; LaPlant, Betsy; Ansell, Stephen M.; Kuruvilla, John; Reeder, Craig B.; Thye, Lim Soon; Anderson, D. Mark; Krysiak, Kilannin; Ramirez, Cody; Qi, Jing; Siegel, Barry A.; Griffith, Malachi; Gomez, Felicia; Fehniger, Todd A.

doi:10.1182/blood-2017-09-804641

Cited by 136 publications

(121 citation statements)

References 42 publications

Supporting

Mentioning

115

Contrasting

Order By: Relevance

“…35 Preliminary data with short term follow-up from the phase 2 Consortium Trial of ibrutinib in relapsed/refractory follicular lymphoma reported grade 3-4 infections in 5% of patients and grade 5 pneumonia in 3%. 37 In terms of major hemorrhage, only 1 case was reported as an AE (occurring 19 days after ibrutinib discontinuation) despite 46% of patients receiving concomitant anticoagulation or antiplatelet therapy during the study. Although 44% of patients experienced a serious AE, dose delays and adjustments allowed many patients to remain on therapy (exposure $12 months in 48%; median relative dose intensity 98%), and 38% were continuing ibrutinib at the time of analysis.…”

Section: Discussionmentioning

confidence: 95%

Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma

Noy

Vos

Thiéblemont

et al. 2017

Blood

245

198

View full text Add to dashboard Cite

• Single-agent ibrutinib induced durable remissions (ORR 48%) with a favorable benefit-risk profile in patients with previously treated MZL.• Inhibition of BCR signaling with ibrutinib provides a treatment option without chemotherapy for an MZL population with high unmet need.Marginal zone lymphoma (MZL) is a heterogeneous B-cell malignancy for which no standard treatment exists. MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation. We conducted a multicenter, open-label, phase 2 study to evaluate the efficacy and safety of ibrutinib in previously treated MZL. Patients with histologically confirmed MZL of all subtypes who received ‡1 prior therapy with an anti-CD20 antibody-containing regimen were treated with 560 mg ibrutinib orally once daily until progression or unacceptable toxicity. The primary end point was independent review committee-assessed overall response rate (ORR) by 2007 International Working Group criteria. Among 63 enrolled patients, median age was 66 years (range, 30-92). Median number of prior systemic therapies was 2 (range, 1-9), and 63% received ‡1 prior chemoimmunotherapy. In 60 evaluable patients, ORR was 48% (95% confidence interval [CI], 35-62). With median follow-up of 19.4 months, median duration of response was not reached (95% CI, 16.7 to not estimable), and median progression-free survival was 14.2 months (95% CI, 8.3 to not estimable). Grade ‡3 adverse events (AEs; >5%) included anemia, pneumonia, and fatigue. Serious AEs of any grade occurred in 44%, with grade 3-4 pneumonia being the most common (8%). Rates of discontinuation and dose reductions due to AEs were 17% and 10%, respectively. Single-agent ibrutinib induced durable responses with a favorable benefit-risk profile in patients with previously treated MZL, confirming the role of BCR signaling in this malignancy. As the only approved therapy, ibrutinib provides a treatment option without chemotherapy for MZL. This study is registered at www.clinicaltrials.gov as #NCT01980628. (Blood. 2017;129(16):2224-2232

show abstract

Section: Discussionmentioning

confidence: 95%

Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma

Noy

Vos

Thiéblemont

et al. 2017

Blood

245

198

View full text Add to dashboard Cite

show abstract

“…[9][10][11][12] In addition, this analysis reflects a considerably longer median follow-up period compared with other phase 2 studies in relapsed/refractory FL (19.4 vs. 4.4-6.5 months).…”

Section: 7mentioning

confidence: 95%

“…Andreas Viardot, 5 Kristie A. Blum, 6 Christopher R. Flowers, 7 Wojciech J. Jurczak, 8 Ian W. Flinn, 9 Brad S. Kahl,10 Peter Martin, 11 Yeonhee Kim, 12 Sanatan Shreay, 12 Matthias Will, 13 Bess Sorensen, 13 Madlaina Breuleux, 13 Pier Luigi Zinzani 14 …”

mentioning

confidence: 99%

Efficacy and safety of idelalisib in patients with relapsed, rituximab- and alkylating agent-refractory follicular lymphoma: a subgroup analysis of a phase 2 study

et al. 2016

View full text Add to dashboard Cite

show abstract

“…39,40 At pharmacologic levels, ibrutinib has been shown to augment ADCC and enhance the activity of anti-CD20 monoclonal antibodies such as rituximab. 41 The combination of ibrutinib and rituximab as frontline therapy for FL was recently explored in a phase 2 study.…”

Section: Integrating Novel Combinations Into Frontline Therapymentioning

confidence: 99%

Frontline strategy for follicular lymphoma: are we ready to abandon chemotherapy?

Fowler

2016

Hematology

View full text Add to dashboard Cite

Chemotherapy combinations have been the backbone of therapy for follicular lymphoma, and are associated with high initial response rates. Unfortunately, toxicity and secondary malignancies remain concerns, and most advanced-stage patients still relapse within 5 years, regardless of the regimen. Advances in the understanding of lymphoma biology have resulted in a new generation of noncytotoxic therapeutics with significant activity in follicular lymphoma. Recent studies exploring biological and targeted combinations in the frontline have shown promise, with response rates similar to chemotherapy. However, these regimens are also associated with significant cost as well as a unique toxicity profile. Large randomized studies are underway to compare noncytotoxic regimens with chemotherapy in the frontline, and several new combinations are being tested in the phase 2 setting. Ongoing work to identify predictive biomarkers and investment in mechanistic studies will ultimately lead to the personalization of therapy in the frontline setting for follicular lymphoma. Learning Objectives• To describe the evolution of standard frontline therapy in follicular lymphoma and the outcomes associated with common cytotoxic regimens • To understand the rationale for emerging noncytotoxic combinations and the activity of several regimens currently under study

show abstract

Single-agent ibrutinib in relapsed or refractory follicular lymphoma: a phase 2 consortium trial

Abstract: Key Points Ibrutinib has modest activity in FL with low response rates in rituximab-refractory patients. CARD11 mutations predict for lack of response to ibrutinib.

Cited by 136 publications

References 42 publications

Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma

Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma

Efficacy and safety of idelalisib in patients with relapsed, rituximab- and alkylating agent-refractory follicular lymphoma: a subgroup analysis of a phase 2 study

Frontline strategy for follicular lymphoma: are we ready to abandon chemotherapy?

Contact Info

Product

Resources

About