Long-term follow-up of ibrutinib monotherapy in treatment-naive patients with Waldenstrom macroglobulinemia.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
11
06
2021
accepted:
07
09
2021
revised:
25
08
2021
pubmed:
18
9
2021
medline:
16
2
2022
entrez:
17
9
2021
Statut:
ppublish
Résumé
Herein, we present the final report of a single-center, prospective phase II study evaluating ibrutinib 420 mg once daily in 30 treatment-naive patients with Waldenstrom macroglobulinemia (WM). The present study is registered with ClinicalTrials.Gov (NCT02604511). With a median follow-up of 50 months, the overall, major, and VGPR response rates were 100%, 87%, and 30%. The VGPR rate was numerically but not significantly lower in patients with than without CXCR4 mutations (14% vs. 44%; p = 0.09). The median time to a minor response was 0.9 months, and to a major response was 1.9 months, though were longer in those with mutated CXCR4 at 1.7 months (p = 0.07) and 7.3 months (p = 0.01). Six patients had disease progression. The median progression-free survival (PFS) was not reached, and the 4-year PFS rate was 76%. There was also a non-significant lower 4-year PFS rate in patients with than without CXCR4 mutations (59% vs. 92%; p = 0.06). The most common treatment-related adverse events were fatigue, upper respiratory infection, and hematoma. Atrial fibrillation occurred in 20% of patients. Ibrutinib monotherapy induced durable responses in treatment-naive patients with WM. CXCR4 mutations impacted VGPR attainment, time to major response, and 4-year PFS rate.
Identifiants
pubmed: 34531537
doi: 10.1038/s41375-021-01417-9
pii: 10.1038/s41375-021-01417-9
pmc: PMC8807393
doi:
Substances chimiques
Piperidines
0
ibrutinib
1X70OSD4VX
Adenine
JAC85A2161
Banques de données
ClinicalTrials.gov
['NCT02604511']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
532-539Subventions
Organisme : NCI NIH HHS
ID : P50 CA100707
Pays : United States
Informations de copyright
© 2021. The Author(s).
Références
Hunter ZR, Xu L, Yang G, Zhou Y, Liu X, Cao Y, et al. The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood. 2014;123:1637–46.
doi: 10.1182/blood-2013-09-525808
Treon SP, Xu L, Yang G, Zhou Y, Liu X, Cao Y, et al. MYD88 L265P somatic mutation in Waldenstrom’s macroglobulinemia. N Engl J Med. 2012;367:826–33.
doi: 10.1056/NEJMoa1200710
Yang G, Zhou Y, Liu X, Xu L, Cao Y, Manning RJ, et al. A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenstrom macroglobulinemia. Blood. 2013;122:1222–32.
doi: 10.1182/blood-2012-12-475111
Cao Y, Hunter ZR, Liu X, Xu L, Yang G, Chen J, et al. CXCR4 WHIM-like frameshift and nonsense mutations promote ibrutinib resistance but do not supplant MYD88(L265P) -directed survival signalling in Waldenstrom macroglobulinaemia cells. Br J Haematol. 2015;168:701–7.
doi: 10.1111/bjh.13200
Treon SP, Tripsas CK, Meid K, Warren D, Varma G, Green R, et al. Ibrutinib in previously treated Waldenstrom’s macroglobulinemia. N Engl J Med. 2015;372:1430–40.
doi: 10.1056/NEJMoa1501548
Treon SP, Meid K, Gustine J, Yang G, Xu L, Liu X, et al. Long-term follow-up of ibrutinib monotherapy in symptomatic, previously treated patients with Waldenstrom macroglobulinemia. J Clin Oncol. 2021;39:565–75.
doi: 10.1200/JCO.20.00555
Treon SP, Gustine J, Meid K, Yang G, Xu L, Liu X, et al. Ibrutinib monotherapy in symptomatic, treatment-naive patients with Waldenstrom macroglobulinemia. J Clin Oncol. 2018;36:2755–61.
doi: 10.1200/JCO.2018.78.6426
Kyle RA, Treon SP, Alexanian R, Barlogie B, Bjorkholm M, Dhodapkar M, et al. Prognostic markers and criteria to initiate therapy in Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s macroglobulinemia. Semin Oncol. 2003;30:116–20.
doi: 10.1053/sonc.2003.50038
Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML, et al. Clinicopathological definition of Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia. Semin Oncol. 2003;30:110–5.
doi: 10.1053/sonc.2003.50082
Owen RG, Kyle RA, Stone MJ, Rawstron AC, Leblond V, Merlini G, et al. Response assessment in Waldenstrom macroglobulinaemia: update from the VIth International Workshop. Br J Haematol. 2013;160:171–6.
doi: 10.1111/bjh.12102
Dimopoulos MA, Trotman J, Tedeschi A, Matous JV, Macdonald D, Tam C, et al. Ibrutinib for patients with rituximab-refractory Waldenstrom’s macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial. Lancet Oncol. 2017;18:241–50.
doi: 10.1016/S1470-2045(16)30632-5
Trotman J, Buske C, Tedeschi A, Matous JV, MacDonald D, Tam C, et al. Long-term follow-up of ibrutinib treatment for rituximab-refractory Waldenström’s macroglobulinemia: final analysis of the open-label substudy of the Phase 3 iNNOVATETM Trial. Blood. 2020;136:38–9.
doi: 10.1182/blood-2020-133916
Buske C, Tedeschi A, Trotman J, García-Sanz R, MacDonald D, Leblond V, et al. Five-year follow-up of ibrutinib plus rituximab vs placebo plus rituximab for Waldenstrom’s macroglobulinemia: final analysis from the randomized Phase 3 iNNOVATETM Study. Blood. 2020;136:24–6.
doi: 10.1182/blood-2020-134460
Vos JM, Tsakmaklis N, Patterson CJ, Meid K, Castillo JJ, Brodsky P, et al. CXCL13 levels are elevated in patients with Waldenstrom macroglobulinemia, and are predictive of major response to ibrutinib. Haematologica. 2017;102:e452–e455.
doi: 10.3324/haematol.2017.172627
Castillo JJ, Gustine JN, Meid K, Dubeau T, Severns P, Xu L, et al. Low levels of von Willebrand markers associate with high serum IgM levels and improve with response to therapy, in patients with Waldenstrom macroglobulinaemia. Br J Haematol. 2018;184:1011–4.
doi: 10.1111/bjh.15200
Dimopoulos MA, Garcia-Sanz R, Gavriatopoulou M, Morel P, Kyrtsonis MC, Michalis E, et al. Primary therapy of Waldenstrom macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR): long-term results of a phase 2 study of the European Myeloma Network (EMN). Blood. 2013;122:3276–82.
doi: 10.1182/blood-2013-05-503862
Treon SP, Ioakimidis L, Soumerai JD, Patterson CJ, Sheehy P, Nelson M, et al. Primary therapy of Waldenstrom macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. J Clin Oncol. 2009;27:3830–5.
doi: 10.1200/JCO.2008.20.4677
Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grunhagen U, Losem C, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013;381:1203–10.
doi: 10.1016/S0140-6736(12)61763-2
Dimopoulos MA, Tedeschi A, Trotman J, Garcia-Sanz R, Macdonald D, Leblond V, et al. Phase 3 trial of ibrutinib plus rituximab in Waldenstrom’s macroglobulinemia. N Engl J Med. 2018;378:2399–410.
doi: 10.1056/NEJMoa1802917
Xu L, Hunter ZR, Tsakmaklis N, Cao Y, Yang G, Chen J, et al. Clonal architecture of CXCR4 WHIM-like mutations in Waldenstrom Macroglobulinaemia. Br J Haematol. 2016;172:735–44.
doi: 10.1111/bjh.13897
Castillo JJ, Xu L, Gustine JN, Keezer A, Meid K, Dubeau TE, et al. CXCR4 mutation subtypes impact response and survival outcomes in patients with Waldenstrom macroglobulinaemia treated with ibrutinib. Br J Haematol. 2019;187:356–63.
doi: 10.1111/bjh.16088
Tam CS, Opat S, D’Sa S, Jurczak W, Lee HP, Cull G, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood. 2020;136:2038–50.
doi: 10.1182/blood.2020006844
Guha A, Derbala MH, Zhao Q, Wiczer TE, Woyach JA, Byrd JC, et al. Ventricular arrhythmias following ibrutinib initiation for lymphoid malignancies. J Am Coll Cardiol. 2018;72:697–8.
doi: 10.1016/j.jacc.2018.06.002
Lampson BL, Yu L, Glynn RJ, Barrientos JC, Jacobsen ED, Banerji V, et al. Ventricular arrhythmias and sudden death in patients taking ibrutinib. Blood. 2017;129:2581–4.
doi: 10.1182/blood-2016-10-742437