A phase 1 study of ibrutinib in combination with R-ICE in patients with relapsed or primary refractory DLBCL

Sauter, Craig S.; Matasar, Matthew J.; Schöder, Heiko; Devlin, Sean M.; Drullinsky, Pamela; Gerecitano, John F.; Kumar, Anita; Noy, Ariela; Palomba, M. Lia; Portlock, Carol S.; Straus, David J.; Zelenetz, Andrew D.; McCall, Susan J.; Miller, Shoshana T.; Courtien, Amanda I.; Younes, Anas; Moskowitz, Craig H.

doi:10.1182/blood-2017-08-802561

Cited by 57 publications

(42 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, a recently published phase I clinical trial of ibrutinib + ICE in RR DLBCL was found to be tolerable without any dose‐limiting toxicities at doses up to 840 mg of ibrutinib and reported an ORR of 90% (11 CR, 7 partial response (PR) to 20 patients) . In this study, all patients with non‐GCB disease who completed at least 1 cycle of therapy achieved a CR.…”

Section: Rr Diseasementioning

confidence: 59%

Diffuse large B‐cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment

2019

View full text Add to dashboard Cite

Disease Overview: Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma originating from the germinal center, and it represents a heterogeneous group of diseases with variable outcomes that are differentially characterized by clinical features, cell of origin (COO), molecular features, and most recently, frequently recurring mutations. Diagnosis: DLBCL is ideally diagnosed from an excisional biopsy of a suspicious lymph node, which shows sheets of large cells that disrupt the underlying structural integrity of the follicle center and stain positive for pan-B-cell antigens, such as CD20 and CD79a. COO is determined by immunohistochemical stains, while molecular features such as double-hit or triple-hit disease are determined by fluorescent in situ hybridization analysis. Commercial tests for frequently recurring mutations are currently not routinely used to inform treatment. Risk Stratification: Clinical prognostic systems for DLBCL, including the rituximab International Prognostic Index, age-adjusted IPI, and NCCN-IPI, use clinical factors for the risk stratification of patients, although this does not affect the treatment approach. Furthermore, DLBCL patients with non-germinal center B-cell (GCB)-like DLBCL (activated B-cell like and unclassifiable) have a poorer response to up-front chemoimmunotherapy (CI) compared to patients with GCB-like DLBCL. Those with c-MYC-altered disease alone and in combination with translocations in BCL2 and/or BCL6 (particularly when the MYC translocation partner is immunoglobulin) respond poorly to up-front CI and salvage autologous stem cell transplant at relapse.Risk-Adapted Therapy: This review will focus on differential treatment of DLBCL up-front and at the time of relapse by COO and molecular features.

show abstract

Section: Rr Diseasementioning

confidence: 59%

Diffuse large B‐cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment

2019

View full text Add to dashboard Cite

show abstract

“…Several phase 2 studies with new drug combinations are ongoing, with mostly disappointing results. Recently, the combination of ibrutinib with R‐ICE was reported, with an encouraging response rate of 90% in only 20 patients, warranting a randomized study (Sauter et al , ).…”

Section: Is There a Better Salvage Regimen?mentioning

confidence: 99%

How I manage patients with relapsed/refractory diffuse large B cell lymphoma

2018

View full text Add to dashboard Cite

SummaryDespite progress in the upfront treatment of diffuse large B cell lymphoma (DLBCL), patients still experience relapses. Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard second‐line treatment for relapsed and refractory (R/R) DLBCL. However, half of the patients will not be eligible for transplantation due to ineffective salvage treatment, and the other half will relapse after ASCT. In randomized studies, no salvage chemotherapy regimen is superior to another. The outcomes are affected by the secondary International Prognostic Index at relapse and various biological factors. The strategy is less clear in patients who require third‐line treatment. A multicohort retrospective non‐Hodgkin lymphoma research (SCHOLAR‐1) study conducted in 636 patients with refractory DLBCL showed an objective response rate of 26% (complete response 7%) to the next line of therapy with a median overall survival of 6·3 months. In the case of a response followed by transplantation, long‐term survival can be achieved in DLBCL patients. There is clearly a need for new drugs that improve salvage efficacy. Encouraging results have been reported with chimeric antigen receptor ‐T cell engineering, warranting further studies in a well‐defined control group of refractory patients. The Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) was used as a handy framework to build the discussion.

show abstract

“…Ibrutinib, a Bruton tyrosine kinase inhibitor implicated in the NF‐κB pathway, has also been trialled in combination with R‐ICE in RR DLBCL, including 4 PMBCL patients. Amongst the 4 PMBCL patients there was an ORR of 100%, all demonstrating PR (Sauter et al , ).…”

Section: Novel Therapeutic Approachesmentioning

confidence: 99%

Biology and therapy of primary mediastinal B‐cell lymphoma: current status and future directions

et al. 2019

View full text Add to dashboard Cite

Summary Primary mediastinal B‐cell lymphoma ( PMBCL ) is a distinct disease closely related to classical nodular sclerosing Hodgkin lymphoma. Conventional diagnostic paradigms utilising clinical, morphological and immunophenotypical features can be challenging due to overlapping features with other B‐cell lymphomas. Reliable diagnostic and prognostic biomarkers that are applicable to the conventional diagnostic laboratory are largely lacking. Nuclear factor kappa B ( NF ‐κB) and Janus kinase/signal transducers and activators of transcription ( JAK ‐ STAT ) signalling pathways are characteristically dysregulated in PMBCL and implicated in several aspects of disease pathogenesis, and the latter pathway in host immune evasion. The tumour microenvironment is manipulated by PMBCL tumours to avoid T‐cell mediated destruction via strategies that include loss of tumour cell antigenicity, T‐cell exhaustion and activation of suppressive T‐regulatory cells. R‐ CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) and DA ‐ EPOCH ‐R (dose‐adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab) are the most common first‐line immunochemotherapy regimens. End of treatment positron emission tomography scans are the recommended imaging modality and are being evaluated to stratify patients for radiotherapy. Relapsed/refractory disease has a relatively poor outcome despite salvage immunochemotherapy and subsequent autologous stem cell transplantation. Novel therapies are therefore being developed for treatment‐resistant disease, targeting aberrant cellular signalling and immune evasion.

show abstract

A phase 1 study of ibrutinib in combination with R-ICE in patients with relapsed or primary refractory DLBCL

Cited by 57 publications

References 13 publications

Diffuse large B‐cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment

Diffuse large B‐cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment

How I manage patients with relapsed/refractory diffuse large B cell lymphoma

Biology and therapy of primary mediastinal B‐cell lymphoma: current status and future directions

Contact Info

Product

Resources

About