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Etiology of Ibrutinib Therapy Discontinuation and Outcomes in Patients With Chronic Lymphocytic Leukemia
Open accessAbstract
IMPORTANCE: The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in patients with chronic lymphocytic leukemia (CLL). Reasons for discontinuing therapy with this drug and outcomes following discontinuation have not been evaluated outside of clinical trials with relatively short follow-up. OBJECTIVE: To determine features associated with discontinuation of ibrutinib therapy and outcomes. DESIGN, SETTING, AND PARTICIPANTS: A total of 308 patients participating in 4 sequential trials of ibrutinib at The Ohio State University Comprehensive Cancer Center were included. These clinical trials accrued patients included in this analysis from May 2010 until April 2014, and data were locked in June 2014. MAIN OUTCOMES AND MEASURES: Patients were evaluated for time to therapy discontinuation, reasons for discontinuation, and survival following discontinuation. For patients who discontinued therapy because of disease progression, targeted deep sequencing was performed in samples at baseline and time of relapse. RESULTS: With a median follow-up of 20 months, 232 patients remained on therapy, 31 had discontinued because of disease progression, and 45 had discontinued for other reasons. Disease progression includes Richter's transformation (RT) or progressive CLL. Richter's transformation appeared to occur early and CLL progressions later (cumulative incidence at 12 months, 4.5% [95% CI, 2.0%-7.0%] and 0.3% [95% CI, 0%-1.0%], respectively). Median survival following RT was 3.5 months (95% CI, 0.3-6.0 months) and 17.6 months (95% CI, 4.7 months-"not reached") following CLL progression. Sequencing on peripheral blood from 8 patients with RT revealed 2 with mutations in BTK, and a lymph node sample showed no mutations in BTK or PLCG2. Deep sequencing on 11 patients with CLL progression revealed BTK or PLCG2 mutations in all. These mutations were not identified before treatment in any patient. CONCLUSIONS AND RELEVANCE: This single-institution experience with ibrutinib confirms it to be an effective therapy and identifies, for the first time, baseline factors associated with ibrutinib therapy discontinuation. Outcomes data show poor prognosis after discontinuation, especially for those patients with RT. Finally, sequencing data confirm initial reports associating mutations in BTK and PLCG2 with progression and clearly show that CLL progressions are associated with these mutations, while RT is likely not. TRIAL REGISTRATIONS: clinicaltrials.gov Identifiers:NCT01105247, NCT01217749, NCT01589302, and NCT01578707.
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“In published studies of disease progression during BTKi therapy,approximately 35% of patients were found to have aBTK mutation alone, an additional 10% had a coexisting mutations in PLCG2, 5% of cases had a PLCG2mutation alone, and the remaining 50% were wild-type (WT) for BTK and PLCG2 (Figure 2)(12, 19, 21–31).”
From Resistance Mechanisms and Approach to Chronic Lymphocytic Leukemia after BTK Inhibitor Therapy (2025) · cites this paper as [27]
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“Interestingly, two separate studies observed that there were no PLCγ2 or BTK mutations detected in patients with CLL before Ibrutinib treatment (127, 128).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [128]
In the citing paper
“While the most common ibrutinib-resistant BTK mutant is C481S, other mutants observed in patients include C481R, C481F, C481Y, T474I, and T474S.33”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [33]
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Citations
Cites
A Proportional Hazards Model for the Subdistribution of a Competing Risk
Fine, J. P., & Gray, R. J. (1999) · Journal of the American Statistical Association · doi:10.1080/01621459.1999.10474144 · Cited by 14,290
A Class of $K$-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk
Gray, R. J. (1988) · The Annals of Statistics · doi:10.1214/aos/1176350951 · Cited by 4,957
Clinical staging of chronic lymphocytic leukemia
Rai, K., Sawitsky, A., Ep, C., Chanana, A. D., Levy, R., & Pasternack, B. (1975) · Blood · doi:10.1182/blood.v46.2.219.219 · Cited by 2,789
Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia
Byrd, J. C., Furman, R. R., Coutre, S. E., Flinn, I. W., Burger, J. A., Blum, K. A., Grant, B., Sharman, J. P., Coleman, M., Wierda, W. G., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215637 · Cited by 2,270
Self-citationIdelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia
Furman, R. R., Sharman, J. P., Coutre, S. E., Cheson, B. D., Pagel, J. M., Hillmen, P., Barrientos, J. C., Zelenetz, A. D., Kipps, T. J., Flinn, I. W., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1315226 · Cited by 1,725
Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia
Byrd, J. C., Brown, J. R., O'Brien, S. M., Barrientos, J. C., Kay, N. E., Reddy, N. M., Coutre, S. E., Tam, C. S. L., Mulligan, S. P., Jaeger, U., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1400376 · Cited by 1,665
Self-citationResistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib
Woyach, J. A., Furman, R. R., Liu, T.-M., Ozer, H. G., Zapatka, M., Ruppert, A. S., Xue, L., Li, D. H.-H., Steggerda, S. M., Versele, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1400029 · Cited by 1,275
Self-citationDubovsky, J. A., Beckwith, K. A., Natarajan, G., Woyach, J. A., Jaglowski, S., Zhong, Y., Hessler, J. D., Liu, T.-M., Chang, B. Y., Larkin, K. M., et al. (2013) · Blood · doi:10.1182/blood-2013-06-507947 · Cited by 810
Self-citationHerman, S. E. M., Gordon, A. L., Hertlein, E., Ramanunni, A., Zhang, X., Jaglowski, S., Flynn, J., Jones, J., Blum, K. A., Buggy, J. J., et al. (2011) · Blood · doi:10.1182/blood-2011-01-328484 · Cited by 807
Self-citationPonader, S., Chen, S.-S., Buggy, J. J., Balakrishnan, K., Gandhi, V., Wierda, W. G., Keating, M. J., O'Brien, S., Chiorazzi, N., & Burger, J. A. (2012) · Blood · doi:10.1182/blood-2011-10-386417 · Cited by 640
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Self-citationStilgenbauer, S., Eichhorst, B. F., Schetelig, J., Coutre, S. E., Seymour, J. F., Munir, T., Puvvada, S. D., Wendtner, C., Roberts, A. W., Jurczak, W. J., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30019-5 · Cited by 809
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Buhimschi, A. D., Armstrong, H. A., Toure, M., Jaime-Figueroa, S., Chen, T. L., Lehman, A. M., Woyach, J. A., Johnson, A. J., Byrd, J. C., & Crews, C. M. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00391 · Cited by 394
Self-citationO'Brien, S. M., Furman, R. R., Coutre, S. E., Flinn, I. W., Burger, J. A., Blum, K. A., Sharman, J. P., Wierda, W. G., Jones, J. A., Zhao, W., et al. (2018) · Blood · doi:10.1182/blood-2017-10-810044 · Cited by 387
Self-citationJones, J. A., Mato, A. R., Wierda, W. G., Davids, M. S., Choi, M., Cheson, B. D., Furman, R. R., Lamanna, N., Barr, P. M., Zhou, L., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30909-9 · Cited by 383
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Flinn, I. W., Hillmen, P., Montillo, M., Nagy, Z., Illés, Á., Étienne, G., Delgado, J., Kuss, B. J., Tam, C. S. L., Gasztonyi, Z., et al. (2018) · Blood · doi:10.1182/blood-2018-05-850461 · Cited by 342
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Ahn, I. E., Underbayev, C., Albitar, A., Herman, S. E. M., Tian, X., Maric, I., Arthur, D. C., Wake, L., Pittaluga, S., Yuan, C. M., et al. (2017) · Blood · doi:10.1182/blood-2016-06-719294 · Cited by 341
O'Brien, S. M., Jones, J. A., Coutre, S. E., Mato, A. R., Hillmen, P., Tam, C. S. L., Österborg, A., Siddiqi, T., Thirman, M. J., Furman, R. R., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30212-1 · Cited by 341
Self-citationThe molecular pathogenesis of chronic lymphocytic leukaemia
Fabbri, G., & Dalla‐Favera, R. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.8 · Cited by 290
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Brown, J. R., Hillmen, P., O’Brien, S. J., Barrientos, J. C., Reddy, N. M., Coutre, S. E., Tam, C. S. L., Mulligan, S. P., Jaeger, U., Barr, P. M., et al. (2017) · Leukemia · doi:10.1038/leu.2017.175 · Cited by 244
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Mato, A. R., Hill, B. T., Lamanna, N., Barr, P. M., Ujjani, C. S., Brander, D. M., Howlett, C., Skarbnik, A. P. Z., Cheson, B. D., Zent, C. S., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx031 · Cited by 232
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Lampson, B. L., Yu, L., Glynn, R. J., Barrientos, J. C., Jacobsen, E. D., Banerji, V., Jones, J. A., Walewska, R. J., Savage, K. J. J., Michaud, G. F., et al. (2017) · Blood · doi:10.1182/blood-2016-10-742437 · Cited by 217
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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., et al. (2018) · Blood · doi:10.1182/blood-2017-12-820910 · Cited by 205
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Rossi, D., Spina, V., & Gaïdano, G. (2018) · Blood · doi:10.1182/blood-2018-01-791376 · Cited by 203
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Burger, J. A. (2019) · The Cancer Journal · doi:10.1097/ppo.0000000000000412 · Cited by 200
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Mato, A. R., Nabhan, C., Barr, P. M., Ujjani, C. S., Hill, B. T., Lamanna, N., Skarbnik, A. P. Z., Howlett, C., Pu, J. J., Sehgal, A. R., et al. (2016) · Blood · doi:10.1182/blood-2016-05-716977 · Cited by 195
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Byrd, J. C., Wierda, W. G., Schuh, A., Devereux, S., Chaves, J. M., Brown, J. R., Hillmen, P., Martin, P., Awan, F. T., Stephens, D. M., et al. (2019) · Blood · doi:10.1182/blood.2018884940 · Cited by 183
Self-citationLiu, T.-M., Woyach, J. A., Zhong, Y., Lozanski, A., Lozanski, G., Dong, S., Strattan, E., Lehman, A., Zhang, X., Jones, J. A., et al. (2015) · Blood · doi:10.1182/blood-2015-02-626846 · Cited by 178
Self-citationSong, Y., Zhou, K., Zou, D., Zhou, J., Hu, J., Yang, H., Zhang, H., Ji, J., Xu, W., Jin, J., et al. (2022) · Blood · doi:10.1182/blood.2021014162 · Cited by 178
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Landau, D. A., Sun, C., Rosebrock, D., Herman, S. E. M., Fein, J., Sivina, M., Underbayev, C., Liu, D., Hoellenriegel, J., Ravichandran, S., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02329-y · Cited by 176
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Chen, Q., Jain, N., Ayer, T., Wierda, W. G., Flowers, C. R., O'Brien, S. M., Keating, M. J., Kantarjian, H. M., & Chhatwal, J. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.68.2856 · Cited by 168
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Self-citationWiczer, T. E., Levine, L. B., Brumbaugh, J., Coggins, J., Zhao, Q., Ruppert, A. S., Rogers, K. A., McCoy, A., Mousa, L., Guha, A., et al. (2017) · Blood Advances · doi:10.1182/bloodadvances.2017009720 · Cited by 164
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Patel, V. M., Balakrishnan, K., Бибикова, Е., Ayres, M., Keating, M. J., Wierda, W. G., & Gandhi, V. V. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1446 · Cited by 154
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Zhao, X., Lwin, T., Silva, A., Shah, B. D., Tao, J., Fang, B., Zhang, L., Fu, K., Li, J., Li, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14920 · Cited by 154
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Xu, L., Tsakmaklis, N., Yang, G., Chen, J. G., Liu, X., Demos, M. G., Kofides, A., Patterson, C. J., Meid, K., Gustine, J. N., et al. (2017) · Blood · doi:10.1182/blood-2017-01-761726 · Cited by 140
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Wang, L., Qin, W. D., Huo, Y., Li, X., Shi, Q., Rasko, J. E. J., Janin, A., & Zhao, W. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0113-2 · Cited by 146
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Self-citationTillman, B. F., Pauff, J. M., Satyanarayana, G., Talbott, M., & Warner, J. L. (2017) · European Journal Of Haematology · doi:10.1111/ejh.13020 · Cited by 138
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Özer, H. G., El‐Gamal, D., Powell, B., Hing, Z. A., Blachly, J. S., Harrington, B. K., Mitchell, S. R., Grieselhuber, N. R., Williams, K., Lai, T.-H., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0902 · Cited by 136
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Self-citationKadri, S., Lee, J., Fitzpatrick, C., Galanina, N., Sukhanova, M., Venkataraman, G., Sharma, S., Long, B., Petras, K., Theissen, M., et al. (2017) · Blood Advances · doi:10.1182/bloodadvances.2016003632 · Cited by 133
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Davids, M. S., Kim, H. T., Nicotra, A., Savell, A., Francoeur, K., Hellman, J. M., Bazemore, J., Miskin, H. P., Sportelli, P., Stampleman, L. V., et al. (2018) · The Lancet Haematology · doi:10.1016/s2352-3026(18)30196-0 · Cited by 117
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Jackson, J. T., Mulazzani, E., Nutt, S. L., & Masters, S. L. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100905 · Cited by 113
“Interestingly, two separate studies observed that there were no PLCγ2 or BTK mutations detected in patients with CLL before Ibrutinib treatment (127, 128).”
BackgroundKharfan‐Dabaja, M. A., Kumar, A., Hamadani, M., Stilgenbauer, S., Ghia, P., Anasetti, C., Dreger, P., Montserrat, E., Perales, M., Alyea, E. P., et al. (2016) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2016.09.013 · Cited by 108
Self-citationRobinson, H. R., Qi, J., Cook, E. M., Nichols, C., Dadashian, E. L., Underbayev, C., Herman, S. E. M., Saba, N. S., Keyvanfar, K., Sun, C., et al. (2018) · Blood · doi:10.1182/blood-2018-02-830992 · Cited by 108
Rogers, K. A., Huang, Y., Ruppert, A. S., Awan, F. T., Heerema, N. A., Hoffman, C., Lozanski, G., Maddocks, K. J., Moran, M. E., Reid, M. A., et al. (2018) · Blood · doi:10.1182/blood-2018-05-853564 · Cited by 107
Self-citationAhn, I. E., Tian, X., Ipe, D., Cheng, M. L., Albitar, M. X., Tsao, L. C., Zhang, L., Ma, W., Herman, S. E. M., Gaglione, E. M., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.20.00979 · Cited by 108
Chronic lymphocytic leukemia: from molecular pathogenesis to novel therapeutic strategies
Delgado, J., Nadeu, F., Colomer, D., & Campo, E. (2020) · Haematologica · doi:10.3324/haematol.2019.236000 · Cited by 113
Nakhoda, S., Vistarop, A., & Wang, Y. L. (2023) · British Journal of Haematology · doi:10.1111/bjh.18418 · Cited by 104
Dreger, P., Ghia, P., Schetelig, J., van Gelder, M., Kimby, E. K., Michallet, M., Moreno, C., Robak, T., Stilgenbauer, S., & Montserrat, E. (2018) · Blood · doi:10.1182/blood-2018-01-826008 · Cited by 105
A pilot study of lower doses of ibrutinib in patients with chronic lymphocytic leukemia
Chen, L. S., Bose, P., Cruz, N. D., Jiang, Y., Wu, Q., Thompson, P. A., Feng, S., Kroll, M. H., Qiao, W., Huang, X., et al. (2018) · Blood · doi:10.1182/blood-2018-06-860593 · Cited by 105
Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies
Gu, D., Tang, H., Wu, J., Li, J., & Miao, Y. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01049-7 · Cited by 100
Kanagal‐Shamanna, R., Jain, P., Patel, K. P., Routbort, M., Bueso‐Ramos, C., Alhalouli, T., Khoury, J. D., Luthra, R., Ferrajoli, A., Keating, M., et al. (2019) · Cancer · doi:10.1002/cncr.31831 · Cited by 98
Paludo, J., Abeykoon, J. P., Shreders, A. J., Ansell, S. M., Kumar, S. K., Ailawadhi, S., King, R. L., Koehler, A. B., Reeder, C. B., Buadi, F. K., et al. (2018) · Annals of Hematology · doi:10.1007/s00277-018-3311-z · Cited by 98
Ibrutinib Resistance Mechanisms and Treatment Strategies for B-Cell Lymphomas
George, B., Chowdhury, S. M., Hart, A., Sircar, A., Singh, S. K., Nath, U. K., Mamgain, M., Singhal, N. K., Sehgal, L., & Jain, N. K. (2020) · Cancers · doi:10.3390/cancers12051328 · Cited by 97
Shadman, M. S., Flinn, I. W., Levy, M. Y., Porter, R. F., Burke, J. M., Zafar, S. F., Misleh, J. G., Kingsley, E. C., Yimer, H. A., Freeman, B., et al. (2022) · The Lancet Haematology · doi:10.1016/s2352-3026(22)00320-9 · Cited by 96
Ibrutinib inhibition of Bruton protein-tyrosine kinase (BTK) in the treatment of B cell neoplasms
Roskoski, R. J. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.09.011 · Cited by 94
Yeh, P. S.-H., Hunter, T., Sinha, D., Ftouni, S., Wallach, E., Jiang, D. H. S., Chan, Y.-C., Wong, S. Q., Silva, M. J., Vedururu, R., et al. (2017) · Nature Communications · doi:10.1038/ncomms14756 · Cited by 93
Blombery, P., Thompson, E. R., Lew, T. E., Tiong, I. S., Bennett, R., Cheah, C. Y., Lewis, K. L., Handunnetti, S. M., Tang, C. P. S., Roberts, A., et al. (2022) · Blood Advances · doi:10.1182/bloodadvances.2022008325 · Cited by 91
Wiestner, A. U. (2015) · Haematologica · doi:10.3324/haematol.2014.119123 · Cited by 92
Genomic and transcriptomic correlates of Richter transformation in chronic lymphocytic leukemia
Klintman, J., Appleby, N., Stamatopoulos, B., Ridout, K., Eyre, T. A., Robbe, P., Pascua, L. L., Knight, S. J. L., Dreau, H. M.-P., Cabes, M., et al. (2020) · Blood · doi:10.1182/blood.2020005650 · Cited by 92
Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL
Sharma, S., Galanina, N., Guo, A., Lee, J., Kadri, S., Van Slambrouck, C., Long, B., Wang, W., Ming, M., Furtado, L. V., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.11932 · Cited by 90
Phospholipase C families: Common themes and versatility in physiology and pathology
Katan, M., & Cockcroft, S. (2020) · Progress in Lipid Research · doi:10.1016/j.plipres.2020.101065 · Cited by 89
Chen, J. G., Liu, X., Munshi, M., Xu, L., Tsakmaklis, N., Demos, M. G., Kofides, A., Guerrera, M. L., Chan, G. G., Patterson, C. J., et al. (2018) · Blood · doi:10.1182/blood-2017-10-811752 · Cited by 88
Naeem, A., Utro, F., Wang, Q., Cha, J., Vihinen, M., Martindale, S., Zhou, Y., Ren, Y., Tyekucheva, S., Kim, A. S., et al. (2023) · Blood Advances · doi:10.1182/bloodadvances.2022008447 · Cited by 87
Evolutionary history of transformation from chronic lymphocytic leukemia to Richter syndrome
Parry, E. M., Leshchiner, I., Guièze, R., Johnson, C., Tausch, E., Parikh, S. A., Lemvigh, C. K., Broséus, J., Hergalant, S., Messer, C., et al. (2023) · Nature Medicine · doi:10.1038/s41591-022-02113-6 · Cited by 87
Byrd, J. C., Smith, S. D., Wagner‐Johnston, N. D., Sharman, J. P., Chen, A. I., Advani, R. H., Augustson, B. M., Marlton, P. V., Commerford, S. R., Okrah, K., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.24310 · Cited by 84
Self-citationRogers, K. A., Huang, Y., Ruppert, A. S., Salem, G., Stephens, D. M., Heerema, N. A., Andritsos, L. A., Awan, F. T., Byrd, J. C., Flynn, J. M., et al. (2017) · British Journal of Haematology · doi:10.1111/bjh.15035 · Cited by 82
Self-citationBTK Inhibitors in Chronic Lymphocytic Leukemia: Biological Activity and Immune Effects
Palma, M., Mulder, T. A., & Österborg, A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.686768 · Cited by 83
Brown, J. R., Harb, W. A., Hill, B. T., Gabrilove, J. L., Sharman, J. P., Schreeder, M. T., Barr, P. M., Foran, J. M., Miller, T., Burger, J. A., et al. (2016) · Haematologica · doi:10.3324/haematol.2015.140806 · Cited by 81
Estupiñán, H. Y., Wang, Q., Berglöf, A., Schaafsma, G. C. P., Shi, Y., Zhou, L., Mohammad, D. K., Yu, L., Vihinen, M., Zain, R., et al. (2021) · Leukemia · doi:10.1038/s41375-021-01123-6 · Cited by 80
He, R. L., Ding, W., Viswanatha, D. S., Chen, D., Shi, M., Dyke, D. L. V., Tian, S., Dao, L. N., Parikh, S. A., Shanafelt, T. D., et al. (2018) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001077 · Cited by 80
Targeted therapies for CLL: Practical issues with the changing treatment paradigm
Jain, N., & O'Brien, S. M. (2015) · Blood Reviews · doi:10.1016/j.blre.2015.12.002 · Cited by 76
Ibrutinib discontinuation in Waldenström macroglobulinemia: Etiologies, outcomes, and IgM rebound
Gustine, J. N., Meid, K., Dubeau, T. E., Severns, P., Hunter, Z. R., Yang, G., Xu, L., Treon, S. P., & Castillo, J. J. (2017) · American Journal of Hematology · doi:10.1002/ajh.25023 · Cited by 76
Genetic and Non-Genetic Mechanisms of Resistance to BCR Signaling Inhibitors in B Cell Malignancies
Ondrišová, L., & Mráz, M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.591577 · Cited by 77
Agathanggelou, A., Smith, E., Davies, N. J., Kwok, M., Zlatanou, A., Oldreive, C. E., Mao, J., Da Costa, D., Yadollahi, S., Perry, T., et al. (2017) · Blood · doi:10.1182/blood-2016-12-758219 · Cited by 75
Chronic Lymphocytic LeukemiaPreprint
Chiorazzi, N., Chen, S., & Rai, K. R. (2020) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a035220 · Cited by 77
BTK and PLCG2 remain unmutated in one-third of patients with CLL relapsing on ibrutinib
Bonfiglio, S., Sutton, L., Ljungström, V., Capasso, A., Pandzic, T., Weström, S., Asl, H. F., Skaftason, A., Gellerbring, A., Lyander, A., et al. (2023) · Blood Advances · doi:10.1182/bloodadvances.2022008821 · Cited by 75
Lampson, B. L., & Brown, J. R. (2018) · Expert Review of Hematology · doi:10.1080/17474086.2018.1435268 · Cited by 74
Flinn, I. W., Gribben, J. G., Dyer, M. J. S., Wierda, W. G., Maris, M. B., Furman, R. R., Hillmen, P., Rogers, K. A., Iyer, S. P., Quillet‐Mary, A., et al. (2019) · Blood · doi:10.1182/blood-2019-01-896290 · Cited by 74
Self-citation
Metadata
- Authors
- Maddocks, K. J., Ruppert, A. S., Lozanski, G., Heerema, N. A., Zhao, W., Abruzzo, L., Lozanski, A., Davis, M., Gordon, A., Smith, L. L., Mantel, R., Jones, J. A., Flynn, J. M., Jaglowski, S. M., Andritsos, L. A., Awan, F., Blum, K. A., Grever, M. R., Johnson, A. J., Byrd, J. C., & Woyach, J. A.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Woyach, Jennifer A.
- ORCID
- Venue
- JAMA Oncology
- Publisher
- American Medical Association (AMA)
- Published
- 2015-04-01
- Volume
- 1
- Issue
- 1
- Pages
- 80
- ISSN
- 2374-2437 (ISSN-L)
- PMC
- PMC4520535
- OpenAlex
- W1999128869
- Cited by
- 584
- References
- 21
- Citations by year
- 2026: 13 · 2025: 29 · 2024: 35 · 2023: 38 · 2022: 47 · 2021: 59 · 2020: 65 · 2019: 72 · 2018: 60 · 2017: 85 · 2016: 64 · 2015: 16
- FWCI
- 41.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Oncology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (4p01ca081534-16)
- National Cancer Institute (P01CA095426, U10CA180861, P50CA140158, R01CA183444, P01CA95426, K23CA178183, R01CA177292, P01-CA-081534)
- Topics
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Acute Lymphoblastic Leukemia research
- Keywords
- chronic lymphocytic leukemia, BTK inhibitors, treatment discontinuation, Richter transformation, BTK mutations, PLCG2 mutations, relapse, deep sequencing, prognostic factors, sequential clinical trials, targeted therapy resistance
- MeSH terms
- Agammaglobulinaemia Tyrosine Kinase, Adenine, Adult, Aged, Aged, 80 and over, Clinical Trials as Topic, DNA Mutational Analysis, Female, Humans, Male, Middle Aged, Mutation, Ohio, Piperidines, Protein-Tyrosine Kinases, Pyrazoles, Pyrimidines, Recurrence, Risk Factors, Time Factors, Biomarkers, Tumor, Leukemia, Lymphocytic, Chronic, B-Cell, Treatment Outcome, Disease Progression, Protein Kinase Inhibitors, Phospholipase C gamma, Kaplan-Meier Estimate, Molecular Targeted Therapy, High-Throughput Nucleotide Sequencing
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