CoChat
Sign Up
Cited by 205Chronic Lymphocytic Leukemia ResearchLymphoma Diagnosis and TreatmentMultiple Myeloma Research and Treatments

Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase 2 study

Open access
Ahn, Inhye E., Farooqui, Mohammed Z. H., Tian, Xin, Valdez, Janet, Sun, Clare, Soto, Susan, Lotter, Jennifer, Housel, Stephanie +16 more·2018·Blood
DOI 10.1182/blood-2017-12-820910PMC PMC5969380
Open this paper in CoChat — free account

Abstract

= .023). In the elderly cohort, the estimated 5-year PFS and OS in RR-CLL were 64.8% and 71.6%, respectively, and no event occurred in TN-CLL. Long-term administration of ibrutinib was well tolerated and provided durable disease control for most patients. This trial was registered at www.clinicaltrials.gov as #NCT01500733.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1182/blood-2017-12-820910

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Duration of response with a BTKi is longer in settings where clonal complexity and evolutionary potential are lower, such as in treatment-naïve cases.

    “Duration of response with a BTKi is longer in settings where clonal complexity and evolutionary potential are lower, such as in treatment-naïve cases(12, 14, 17).”

    From Resistance Mechanisms and Approach to Chronic Lymphocytic Leukemia after BTK Inhibitor Therapy (2025) · cites this paper as [14]

    The Results (Disease progression and survival; page not available in our copy) report more favorable progression-free survival with first-line ibrutinib than with treatment after relapse, supporting the longer-durability comparison for treatment-naïve CLL. The paper does not establish that lower clonal complexity or evolutionary potential explains that difference; the Discussion identifies prior treatment history and TP53 aberration as determinants of progression-free survival. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 36

  1. [1]Fischer K, Bahlo J, Fink AM, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016;127(2):208-215. [DOI] [PubMed] [Google Scholar]
  2. [2]Thompson PA, Tam CS, O’Brien SM, et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood. 2016;127(3):303-309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. [3]Landau DA, Tausch E, Taylor-Weiner AN, et al. Mutations driving CLL and their evolution in progression and relapse. Nature. 2015;526(7574):525-530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. [4]Hallek M, Fischer K, Fingerle-Rowson G, et al. ; German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376(9747):1164-1174. [DOI] [PubMed] [Google Scholar]
  5. [5]Stilgenbauer S, Schnaiter A, Paschka P, et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood. 2014;123(21):3247-3254. [DOI] [PubMed] [Google Scholar]
  6. [6]Eichhorst B, Fink AM, Bahlo J, et al. ; German CLL Study Group (GCLLSG). First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016;17(7):928-942. [DOI] [PubMed] [Google Scholar]
  7. [7]Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101-1110. [DOI] [PubMed] [Google Scholar]
  8. [8]Hillmen P, Robak T, Janssens A, et al. ; COMPLEMENT 1 Study Investigators. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015;385(9980):1873-1883. [DOI] [PubMed] [Google Scholar]
  9. [9]Byrd JC, Brown JR, O’Brien S, et al. ; RESONATE Investigators. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. [10]Burger JA, Tedeschi A, Barr PM, et al. ; RESONATE-2 Investigators. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425-2437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. [11]O’Brien S, Jones JA, Coutre SE, et al. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study. Lancet Oncol. 2016;17(10):1409-1418. [DOI] [PubMed] [Google Scholar]
  12. [12]Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997-1007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. [13]Amrein PC, Attar EC, Takvorian T, et al. Phase II study of dasatinib in relapsed or refractory chronic lymphocytic leukemia. Clin Cancer Res. 2011;17(9):2977-2986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. [14]Herishanu Y, Pérez-Galán P, Liu D, et al. The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood. 2011;117(2):563-574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. [15]Dühren-von Minden M, Übelhart R, Schneider D, et al. Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling. Nature. 2012;489(7415):309-312. [DOI] [PubMed] [Google Scholar]
  16. [16]Minici C, Gounari M, Übelhart R, et al. Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukaemia. Nat Commun. 2017;8:15746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. [17]Burger JA, Wiestner A. Targeting B cell receptor signalling in cancer: preclinical and clinical advances. Nat Rev Cancer. 2018;18(3):148-167. [DOI] [PubMed] [Google Scholar]
  18. [18]Herman SE, Mustafa RZ, Gyamfi JA, et al. Ibrutinib inhibits BCR and NF-κB signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL. Blood. 2014;123(21):3286-3295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. [19]Cheng S, Ma J, Guo A, et al. BTK inhibition targets in vivo CLL proliferation through its effects on B-cell receptor signaling activity. Leukemia. 2014;28(3):649-657. [DOI] [PubMed] [Google Scholar]
  20. [20]Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32-42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. [21]Farooqui MZ, Valdez J, Martyr S, et al. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial. Lancet Oncol. 2015;16(2):169-176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. [22]Furman RR, Cheng S, Lu P, et al. Ibrutinib resistance in chronic lymphocytic leukemia. N Engl J Med. 2014;370(24):2352-2354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. [24]Burger JA, Landau DA, Taylor-Weiner A, et al. Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition. Nat Commun. 2016;7:11589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. [25]Ahn IE, Underbayev C, Albitar A, et al. Clonal evolution leading to ibrutinib resistance in chronic lymphocytic leukemia. Blood. 2017;129(11):1469-1479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. [26]Woyach JA, Ruppert AS, Guinn D, et al. BTKC481S-mediated resistance to ibrutinib in chronic lymphocytic leukemia. J Clin Oncol. 2017;35(13):1437-1443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. [27]Kadri S, Lee J, Fitzpatrick C, et al. Clonal evolution underlying leukemia progression and Richter transformation in patients with ibrutinib-relapsed CLL. Blood Adv. 2017;1(12):715-727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. [30]Brown JR, Moslehi J, O’Brien S, et al. Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials. Haematologica. 2017;102(10):1796-1805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. [31]Sun C, Tian X, Lee YS, et al. Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib. Blood. 2015;126(19):2213-2219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. [32]Ahn IE, Jerussi T, Farooqui M, Tian X, Wiestner A, Gea-Banacloche J. Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib. Blood. 2016;128(15):1940-1943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. [33]Lionakis MS, Dunleavy K, Roschewski M, et al. Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma. Cancer Cell. 2017;31(6):833-843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. [34]Hallek M, Cheson BD, Catovsky D, et al. ; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines [published e-Letter response 4 June 2012]. Blood. 2008;111(12):5446-5456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. [35]Rawstron AC, Böttcher S, Letestu R, et al. ; European Research Initiative in CLL. Improving efficiency and sensitivity: European Research Initiative in CLL (ERIC) update on the international harmonised approach for flow cytometric residual disease monitoring in CLL. Leukemia. 2013;27(1):142-149. [DOI] [PubMed] [Google Scholar]
  33. [36]Böttcher S, Ritgen M, Fischer K, et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol. 2012;30(9):980-988. [DOI] [PubMed] [Google Scholar]
  34. [37]Strati P, Keating MJ, O’Brien SM, et al. Outcomes of first-line treatment for chronic lymphocytic leukemia with 17p deletion. Haematologica. 2014;99(8):1350-1355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. [38]Byrd JC, Furman RR, Coutre SE, et al. Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood. 2015;125(16):2497-2506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. [39]Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016;17(6):768-778. [DOI] [PubMed] [Google Scholar]

Cited by

Sorted by citations

Authors
Ahn, I. E., Farooqui, M. Z. H., Tian, X., Valdez, J., Sun, C., Soto, S., Lotter, J., Housel, S., Stetler-Stevenson, M., Yuan, C. M., Maric, I., Calvo, K. R., Nierman, P., Hughes, T. E., Saba, N. S., Marti, G. E., Pittaluga, S., Herman, S. E. M., Niemann, C. U., Pedersen, L. B., Geisler, C. H., Childs, R., Aue, G., & Wiestner, A.
Affiliations
  • Hematology Branch and
  • National Institutes of Health (US)
  • Leidos Biomedical Research Inc. (United States) (US)
  • Laboratory of Pathology, Center for Cancer Research, National Cancer Institute,
  • National Cancer Institute (UA)
  • Department of Laboratory Medicine, Clinical Research Center, and
  • Tulane University (US)
  • Copenhagen University Hospital (DK)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2018-05-24
Volume
131
Issue
21
Pages
2357-2366
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2017-12-820910
PMC
PMC5969380
OpenAlex
W2790448887
Cited by
205
References
3
Citations by year
2026: 8 · 2025: 16 · 2024: 5 · 2023: 23 · 2022: 21 · 2021: 36 · 2020: 42 · 2019: 35 · 2018: 19
FWCI
18.71
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Novo Nordisk Fonden (NNF16OC0019302)
  • National Institute of General Medical Sciences (U54GM104940)
Topics
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
Keywords
ibrutinib, chronic lymphocytic leukemia, long-term follow-up, progression-free survival, overall survival, relapsed/refractory CLL, treatment-naive CLL, drug tolerability, durable disease control
MeSH terms
Adenine, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Bone Marrow, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Staging, Piperidines, Pyrazoles, Pyrimidines, Leukemia, Lymphocytic, Chronic, B-Cell, Treatment Outcome, Neoplasm, Residual, Protein Kinase Inhibitors, Kaplan-Meier Estimate

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review