Skip to main content
Erschienen in:

20.12.2021 | short review

BTKi, venetoclax, obinutuzumab: what is the ideal combination?

verfasst von: Daniel Heintel, MD

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 1/2022

Einloggen, um Zugang zu erhalten

Summary

Chronic lymphocytic leukemia (CLL) treatment strategies have improved and changed dramatically in the last few years. Currently, patients are mostly treated with so-called novel agents, including Bruton tyrosin kinase (BTK) inhibitors and BCL‑2 inhibitors. CLL is a chronic disease; therefore, a proportion of patients will require multiple lines of therapy. In this review, we present the current treatment options for patients with CLL and discuss potential optimal treatment combinations.
Literatur
1.
Zurück zum Zitat Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:452–67.CrossRef Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:452–67.CrossRef
2.
Zurück zum Zitat Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, et al. SEER cancer statistics review. Bethesda: National Cancer Institute; 2019. pp. 1975–2016. Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, et al. SEER cancer statistics review. Bethesda: National Cancer Institute; 2019. pp. 1975–2016.
3.
Zurück zum Zitat Eichhorst B, Robak T, Montserrat E, Ghia P, Niemann CU, Kater AP et al. Chronic lymphocytic leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32:23–33.CrossRef Eichhorst B, Robak T, Montserrat E, Ghia P, Niemann CU, Kater AP et al. Chronic lymphocytic leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32:23–33.CrossRef
4.
Zurück zum Zitat Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H et al. IwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745–2760.CrossRef Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H et al. IwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745–2760.CrossRef
5.
Zurück zum Zitat Döhner H, Stilgenbauer S, Benner A, Leupolt E, Kröber A, Bullinger L, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343:1910–6.CrossRef Döhner H, Stilgenbauer S, Benner A, Leupolt E, Kröber A, Bullinger L, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343:1910–6.CrossRef
6.
Zurück zum Zitat Zenz T, Eichhorst B, Busch R, Denzel T, Häbe S, Winkler D et al. TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol. 2010;28:4473–9.CrossRef Zenz T, Eichhorst B, Busch R, Denzel T, Häbe S, Winkler D et al. TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol. 2010;28:4473–9.CrossRef
7.
Zurück zum Zitat Stilgenbauer S, Schnaiter A, Paschka P, Zenz T, Rossi M, Döhner K et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood. 2014;123:3247–54.CrossRef Stilgenbauer S, Schnaiter A, Paschka P, Zenz T, Rossi M, Döhner K et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood. 2014;123:3247–54.CrossRef
8.
Zurück zum Zitat Tausch E, Schneider C, Robrecht S, Zhang C, Dolnik A, Bloehdorn J et al. Prognostic and predictive impact of genetic markers in patients with CLL treated with obinutuzumab and venetoclax. Blood. 2020;135:2402–12.CrossRef Tausch E, Schneider C, Robrecht S, Zhang C, Dolnik A, Bloehdorn J et al. Prognostic and predictive impact of genetic markers in patients with CLL treated with obinutuzumab and venetoclax. Blood. 2020;135:2402–12.CrossRef
9.
Zurück zum Zitat O’Brien S, Furman RR, Coutre S, Flinn IW, Burger JA, Blum K et al. Single-agent Ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia: a 5‑year experience. Blood. 2018;131:1910–9.CrossRef O’Brien S, Furman RR, Coutre S, Flinn IW, Burger JA, Blum K et al. Single-agent Ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia: a 5‑year experience. Blood. 2018;131:1910–9.CrossRef
10.
Zurück zum Zitat Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib–rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med 2019;381:432–443.CrossRef Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib–rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med 2019;381:432–443.CrossRef
11.
Zurück zum Zitat Woyach JA, Ruppert AS, Heerema NA, Zhao W, Booth AM, Ding W, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379(26):2517–2528.CrossRef Woyach JA, Ruppert AS, Heerema NA, Zhao W, Booth AM, Ding W, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379(26):2517–2528.CrossRef
12.
Zurück zum Zitat Kater AP, Seymour JF, Hillmen P, Eichhorst B, Langerak AW, Owen C, et al. Fixed duration of venetoclax-rituximab in relapsed/refractory chronic lymphocytic leukemia eradicates minimal residual disease and prolongs survival: post-treatment follow-up of the Murano phase III study. J Clin Oncol. 2019;37(4):269–277.CrossRef Kater AP, Seymour JF, Hillmen P, Eichhorst B, Langerak AW, Owen C, et al. Fixed duration of venetoclax-rituximab in relapsed/refractory chronic lymphocytic leukemia eradicates minimal residual disease and prolongs survival: post-treatment follow-up of the Murano phase III study. J Clin Oncol. 2019;37(4):269–277.CrossRef
13.
Zurück zum Zitat Al-Sawaf O, Zhang C, Tandon M, Sinha A, Fink AM, Robrecht S, et al. Fixed-duration venetoclax–obinutuzumab for previously untreated patients with chronic lymphocytic leukemia: follow-up of efficacy and safety results from the multicenter, open-label, randomized, phase III CLL14 trial. J Clin Oncol. 2020;21(9):1188–1200. Al-Sawaf O, Zhang C, Tandon M, Sinha A, Fink AM, Robrecht S, et al. Fixed-duration venetoclax–obinutuzumab for previously untreated patients with chronic lymphocytic leukemia: follow-up of efficacy and safety results from the multicenter, open-label, randomized, phase III CLL14 trial. J Clin Oncol. 2020;21(9):1188–1200.
14.
Zurück zum Zitat Cheng S, Ma J, Guo A, Lu P, Leonard JP, Coleman M, et al. BTK inhibition targets in vivo CLL proliferation through its effects on B‑cell receptor signaling activity. Leukemia. 2014;28:649–57.CrossRef Cheng S, Ma J, Guo A, Lu P, Leonard JP, Coleman M, et al. BTK inhibition targets in vivo CLL proliferation through its effects on B‑cell receptor signaling activity. Leukemia. 2014;28:649–57.CrossRef
15.
Zurück zum Zitat Herman SEM, Mustafa RZ, Gyamfi JA, Pittaluga S, Chang S, Chang B, et al. Ibrutinib inhibits BCR and NF-KB signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL key points. Blood J Am Soc Hematol. 2014;123:3286–95. Herman SEM, Mustafa RZ, Gyamfi JA, Pittaluga S, Chang S, Chang B, et al. Ibrutinib inhibits BCR and NF-KB signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL key points. Blood J Am Soc Hematol. 2014;123:3286–95.
16.
Zurück zum Zitat Moreno C, Greil R, Demirkan F, Tedeschi A, Anz B, Larratt L, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (ILLUMINATE): a multicentre, Randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(1):43–56.CrossRef Moreno C, Greil R, Demirkan F, Tedeschi A, Anz B, Larratt L, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (ILLUMINATE): a multicentre, Randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(1):43–56.CrossRef
17.
Zurück zum Zitat Covey T, Gulranjani M, Cheung J, Bibikova E, Clevenger T, Krantz F, et al. Pharmacodynamic evaluation of acalabrutinib in relapsed/refractory and treatment-naive patients with chronic lymphocytic leukemia (CLL) in the phase 1/2 ACE-CL-001 study. Blood. 2020;26(12):2800–2809. Covey T, Gulranjani M, Cheung J, Bibikova E, Clevenger T, Krantz F, et al. Pharmacodynamic evaluation of acalabrutinib in relapsed/refractory and treatment-naive patients with chronic lymphocytic leukemia (CLL) in the phase 1/2 ACE-CL-001 study. Blood. 2020;26(12):2800–2809.
18.
Zurück zum Zitat Barf T, Covey T, Izumi R, van de Kar B, Gulrajani M, van Lith B, van Hoek M, de Zwart E, Mittag D, Demont D, Verkaik S, Krantz F, Pearson PG, Ulrich R, Kaptein A. Acalabrutinib (ACP-196): A Covalent Bruton Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In Vivo Potency Profile. J Pharmacol Exp Ther. 2017;363(2):240–252.CrossRef Barf T, Covey T, Izumi R, van de Kar B, Gulrajani M, van Lith B, van Hoek M, de Zwart E, Mittag D, Demont D, Verkaik S, Krantz F, Pearson PG, Ulrich R, Kaptein A. Acalabrutinib (ACP-196): A Covalent Bruton Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In Vivo Potency Profile. J Pharmacol Exp Ther. 2017;363(2):240–252.CrossRef
19.
Zurück zum Zitat Covey T, Barf T, Gulrajani M, Krantz F, van Lith B, Bibikova E, et al. Abstract 2596: ACP-196: a novel covalent Bruton’s tyrosine kinase (Btk) inhibitor with improved selectivity and in vivo target coverage inchronic lymphocytic leukemia (CLL) patients. Cancer Research 2015;75(15 Suppl):2596. Covey T, Barf T, Gulrajani M, Krantz F, van Lith B, Bibikova E, et al. Abstract 2596: ACP-196: a novel covalent Bruton’s tyrosine kinase (Btk) inhibitor with improved selectivity and in vivo target coverage inchronic lymphocytic leukemia (CLL) patients. Cancer Research 2015;75(15 Suppl):2596.
20.
Zurück zum Zitat Byrd JC, Harrington B, O’Brien S, Jones JA, Schuh A, Devereux S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374(4):323–32.CrossRef Byrd JC, Harrington B, O’Brien S, Jones JA, Schuh A, Devereux S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374(4):323–32.CrossRef
21.
Zurück zum Zitat Sharman JP, Egyed M, Jurczak W, Skarbnik A, Pagel JM, Flinn IW, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a Randomised, controlled, phase 3 trial. Lancet. 2020;395(10232):1278–1291CrossRef Sharman JP, Egyed M, Jurczak W, Skarbnik A, Pagel JM, Flinn IW, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a Randomised, controlled, phase 3 trial. Lancet. 2020;395(10232):1278–1291CrossRef
23.
Zurück zum Zitat Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225–2236.CrossRef Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225–2236.CrossRef
24.
Zurück zum Zitat Jain N, Keating M, Thompson P, Ferrajoli A, Burger J, Borthakur G et al. Ibrutinib and Venetoclax for first-line treatment of CLL. N Engl J Med. 2019;380:2095–103.CrossRef Jain N, Keating M, Thompson P, Ferrajoli A, Burger J, Borthakur G et al. Ibrutinib and Venetoclax for first-line treatment of CLL. N Engl J Med. 2019;380:2095–103.CrossRef
25.
Zurück zum Zitat Hillmen P, Rawstron AC, Brock K, Muñoz-Vicente S, Yates FJ, Bishop R et al. Ibrutinib plus venetoclax in relapsed/refractory chronic lymphocytic leukemia: the CLARITY study. J Clin Oncol. 2019;37:2722–9.CrossRef Hillmen P, Rawstron AC, Brock K, Muñoz-Vicente S, Yates FJ, Bishop R et al. Ibrutinib plus venetoclax in relapsed/refractory chronic lymphocytic leukemia: the CLARITY study. J Clin Oncol. 2019;37:2722–9.CrossRef
Metadaten
Titel
BTKi, venetoclax, obinutuzumab: what is the ideal combination?
verfasst von
Daniel Heintel, MD
Publikationsdatum
20.12.2021
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 1/2022
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-021-00776-4

Weitere Artikel der Ausgabe 1/2022

memo - Magazine of European Medical Oncology 1/2022 Zur Ausgabe