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Clinical Trial
. 2018 Apr 19;131(16):1805-1808.
doi: 10.1182/blood-2017-08-802561. Epub 2018 Jan 31.

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

Craig S Sauter  1   2 , Matthew J Matasar  1   2 , Heiko Schoder  3 , Sean M Devlin  4 , Pamela Drullinsky  1   2 , John Gerecitano  1   2 , Anita Kumar  1   2 , Ariela Noy  1   2 , Maria L Palomba  1   2 , Carol S Portlock  1   2 , David J Straus  1   2 , Andrew D Zelenetz  1   2 , Susan J McCall  1 , Shoshana T Miller  1 , Amanda I Courtien  1 , Anas Younes  1   2 , Craig H Moskowitz  1   2
Affiliations
Clinical Trial

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

Craig S Sauter et al. Blood. .

Abstract

In the postrituximab era, approximately half of the patients with relapsed or refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL) fail to achieve a chemosensitive response to standard salvage therapy, and are thus ineligible to proceed to autologous stem cell transplantation with curative intent. The Bruton tyrosine kinase inhibitor ibrutinib demonstrates single-agent activity in rel/ref DLBCL, particularly of non-germinal center (non-GC) cell of origin. We conducted a single-center phase 1 study evaluating dose-escalated ibrutinib, in a 3-by-3 design, in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in physiologically transplant-eligible rel/ref DLBCL patients. Twenty-one patients have been treated and are evaluable for toxicity with no dose-limiting toxicities observed through expansion with ibrutinib at 840 mg daily at dose level 3. Of the 20 patients evaluable for response, per modern International Conference on Malignant Lymphoma criteria, 11 patients achieved complete remission (CR) and 7 patients achieved partial remission for an overall response rate of 90%. All evaluable patients with non-GC DLBCL achieved a metabolic CR. Ibrutinib in combination with R-ICE demonstrates tolerability and efficacy in rel/ref DLBCL, particularly of non-GC phenotype. This treatment program warrants further investigation in later-phase studies. This trial was registered at www.clinicaltrials.gov as #NCT02219737.

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Conflict of interest statement

Conflict-of-interest disclosure: C.S.S. received research support from Pharmacyclics. M.J.M. received research support and honoraria from Genentech. P.D. received honorarium and served on an advisory board for Seattle Genetics. J.G. received honoraria and served on an advisory board for Samus Therapeutics, Gilead, AbbVie Pharmaceuticals, Genentech, Bayer, Aratana, Arcus Medica, Incyte, Mass Medical International, Merck, Orexo, and Royal Bank of Canada. A.K. received research funding from AbbVie Pharmaceuticals, Adaptive Biotechnologies, Seattle Genetics, Celgene, and Pharmacyclics, and served on an advisory board for Celgene. A.N. received research funding, speaker’s fees, and travel fees from Pharmacyclics. A.D.Z. consulted and served on an advisory board for Genentech, Gilead, Celgene, Janssen, Amgen, Novartis, and Adaptive Biotechnologies; consulted for Pharmacyclics; received research funding from Roche, Gilead, and MEI Pharmaceuticals; and is the Data Monitoring Committee Chair for Beigene. A.Y. received honorarium from Seattle Genetics, Takeda Millennium, Janssen, AbbVie Pharmaceuticals, and Pharmacyclics. C.H.M. consulted for, served on an advisory board for, and received research funding from Seattle Genetics. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Kaplan-Meier survival estimates. (A) EFS, PFS, and OS by ITT. (B) PFS and OS in patients proceeding to transplantation.
See this image and copyright information in PMC

Comment in

References

    1. Philip T, Guglielmi C, Hagenbeek A, et al. . Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med. 1995;333(23):1540-1545. - PubMed
    1. Crump M, Kuruvilla J, Couban S, et al. . Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014;32(31):3490-3496. - PubMed
    1. Gisselbrecht C, Glass B, Mounier N, et al. . Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184-4190. - PMC - PubMed
    1. Barrington SF, Mikhaeel NG, Kostakoglu L, et al. . Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32(27):3048-3058. - PMC - PubMed
    1. Sauter CS, Matasar MJ, Meikle J, et al. . Prognostic value of FDG-PET prior to autologous stem cell transplantation for relapsed and refractory diffuse large B-cell lymphoma. Blood. 2015;125(16):2579-2581. - PMC - PubMed

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