The treatment combination of obinutuzumab, bendamustine and dexamethasone achieved a deeper response than the previous line of treatment in five patients with Waldenström‘s macroglobulinemia

Česká verzia

Authors: Z. Adam; L. Pour; M. Krejčí; V. Sandecká; M. Štork; I. Boichuk; Z. Král
Authors place of work: Interní hematologická a onkologická klinika LF MU a FN Brno
Published in the journal: Klin Onkol 2024; 39(6): 427-432
Category: Original Articles
doi: https://doi.org/10.48095/ccko2024427

Summary

Background: Rituximab is already a standard part of the treatment of patients with Waldenström‘s macroglobulinemia. However, a small proportion of patients develop intolerance to rituximab during administration or the treatment is not very effective. In these patients, we are faced with the question of whether another anti-CD20 monoclonal antibody can be used and what result will be achieved. Patient population and methods: Between 2020 and 2022, we administered the new anti-CD20 monoclonal antibody obinutuzumab in combination with bendamustine and dexamethasone in five patients with Waldenström‘s macroglobulinemia (WM). All patients completed eight cycles of the indicated treatment. Two of them received second-line treatment, another two received third-line treatment, and one patient received this treatment as part of fourth-line treatment. We did not observe significant toxicity (grade III and IV) in any patient. Results: All five patients achieved a deeper treatment response (once complete response, 4-times very good partial response) than in previous lines of treatment. At a median follow-up after treatment of 29 months (range 28–48), the disease relapsed in one patient only, the others are in remission. Conclusion: Obinutuzumab in combination with bendamustine is a very effective treatment alternative for WM. In the described five patients, obinutuzumab with bendamustine and dexamethasone achieved a deeper therapeutic response than the previous treatment lines. Obinutuzumab represents a drug that will be of great benefit to selected patients with WM.

Keywords:

obinutuzumab – Waldenström macroglobulinemia – bendamustine

Zdroje

1. McMaster ML. The epidemiology of Waldenström macroglobulinemia. Semin Hematol 2023; 60 (2): 65–72. doi: 10.1053/j.seminhematol.2023.03.008.

2. Adam Z, Pour L, Zeman D et al. Waldenström’s macroglobulinemia – clinical symptoms and review of therapy yesterday, today and tomorrow. Klein Onkol 2023; 36 (3): 177–191. doi: 10.48095/ccko2023177.

3. Kastritis E, Gavriatopoulou M, Kyrtsonis MC et al. Dexamethasone, rituximab, and cyclophosphamide as primary treatment of Waldenström macroglobulinemia: final analysis of a phase 2 study. Blood 2015; 126 (11): 1392–1394. doi: 10.1182/blood-2015-05-647420.

4. Kaščák M, Hájek R, Minařík J et al. Diagnostika a léčba Waldenströmovy makroglobulinémie. Trans Hematol Dnes 2022; 28 (Suppl 1): S44–S74.

5. Mössner E, Brünker P, Moser P et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new Type II anti-CD20 antibody with enhanced direct and immune effector cell mediated B cell cytotoxicity. Blood 2010; 115 (22): 4393–4402. doi: 10.1182/blood-2009-06-225979.

6. Leblond V, Kastritis E, Advani R et al. Treatment recommendations from the Eighth International Workshop on Waldenström’s macroglobulinemia. Blood 2016; 128 (10): 1321–1328. doi: 10.1182/blood-2016-04-711234.

7. Gavriatopoulou M, Kastritis E, Kyrtsonis MC et al. Phase 2 study of ofatumumab, fludarabine and cyclophosphamide in relapsed/refraktory Waldenström’s macroglobulinemia. Leuk Lymphoma 2017; 58 (6): 1506–1508. doi: 10.1080/10428194.2016.1233541.

8. Furman RR, Eradat HA, DiRienzo CG et al. Once-weekly ofatumumab in untreated or relapsed Waldenström’s macroglobulinaemia: an open-label, single-arm, phase 2 study. Lancet Haematol 2017; 4 (1): e24–e34. doi: 10.1016/S2352-3026 (16) 30166-1.

9. Buske C. Ofatumumab: another way to target CD20 in Waldenström’s macroglobulinaemia? Lancet Haematol 2017; 4 (1): e4–e5. doi: 10.1016/S2352-3026 (16) 30163-6.

10. Sehn LH, Chua N, Mayer J et al. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol 2016; 17 (8): 1081–1093. doi: 10.1016/S1470-2045 (16) 30097-3.

11. García-Muñoz R, López-Díaz-de-Cerio A, Feliu J et al. Follicular lymphoma: in vitro effects of combining lymphokine-activated killer (LAK) cell-induced cytotoxicity and rituximab- and obinutuzumab-dependent cellular cytotoxicity (ADCC) activity. Immunol Res 2016; 64 (2): 548–557. doi: 10.1007/s12026-015-8747-9.

12. Herter S, Herting F, Mundigl O et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther 2013; 12 (10): 2031–2042. doi: 10.1158/1535-7163.MCT-12-1182.

13. Sehn LH, Goy A, Offner FC et al. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol 2015; 33 (30): 3467–3474. doi: 10.1200/JCO.2014.59.2139.

14. Marcus RE, Davies AJ, Ando K et al. Obinutuzumab-based induction and maintenance prolongs Progression-Free Survival (PFS) in patients with previously untreated follicular lymphoma: primary results of the randomized phase 3 GALLIUM study. Blood 2016; 128 (6). doi: 10.1182/blood.V128.22.6.6.

15. Hiddemann W, Barbui AM, Canales MA et al. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol 2018; 36 (23): 2395–2404. doi: 10.1200/JCO.2017.76.8960.

16. Seymour JF, Marcus R, Davies A et al. Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression. Haematologica 2019; 104 (6): 1202–1208. doi: 10.3324/haematol.2018.209015.

17. Jamois C, Gibiansky E, Gibiansky L et al. Role of obinutuzumab exposure on clinical outcome of follicular lymphoma treated with first-line immunochemotherapy. Br J Clin Pharmacol 2019; 85 (7): 1495–1506. doi: 10.1111/bcp.13920.

18. Salles GA, Morschhauser F, Solal-Céligny P et al. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol 2013; 31 (23): 2920–2926. doi: 10.1200/JCO.2012.46.9718.

19. Cheson BD, Chua N, Mayer J et al. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol 2018; 36 (22): 2259–2266. doi: 10.1200/JCO.2017.76.3656.

20. Cheson BD, Trask PC, Gribben JG et al. Health-related quality of life and symptoms in patients with rituximab-refractory indolent non-Hodgkin lymphoma treated in the phase III GADOLIN study with obinutuzumab plus bendamustine versus bendamustine alone. Ann Hematol 2017; 96 (2): 253–259. doi: 10.1007/s00277-016-2878-5.

21. Marcus R, Devies A, Ando K et al. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med 2017; 377 (14): 1331–1344. doi: 10.1056/NEJMoa1614598.

22. Goede V, Fischer K, Engelke A et al. Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study. Leukemia 2015; 29 (7): 1602–1604. doi: 10.1038/leu.2015.14.

23. Vitolo U, Trněný M, Belada D et al. Obinutuzumab or rituximab plus CHOP in patients with previously untreated diffuse large B-cell lymphoma: final results from an open-label, randomized phase 3 study (GOYA). Blood 2016; 128 (22): 470. doi: 10.1182/blood.V128.22.470.470.

24. Sehn LH, Martelli M, Trněný M et al. A randomized, open-label, phase III study of obinutuzumab or rituximab plus CHOP in patients with previously untreated diffuse large B-cell lymphoma: final analysis of GOYA. J Hematol Oncol 2020; 13 (1): 71. doi: 10.1186/s13045-020-00900-7.

25. Casasnovas R-O, Salles GA, Oberic L et al. Obinutuzumab versus rituximab in combination with ACVBP-14 or CHOP-14 following a PET-driven strategy in Aa-IPI 1–3 DLBCL patients (< 60 years): third planned interim and final analyses of the gained trial. Blood 2017; 130 (Suppl 1): 190. Doi 10.1182/blood.V130.Suppl_1.190.190.

26. Herold M, Hoster E, Janssens A et al. Immunochemotherapy and maintenance with obinutuzumab or rituximab in patients with previously untreated marginal zone lymphoma in the randomized GALLIUM trial. Hemasphere 2022; 6 (3): e699. doi: 10.1097/HS9.00000000000 00699.

27. Luo C, Wu G, Huang X et al. Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20<sup>+</sup> B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis. Sci Rep 2021; 11 (1): 3255. doi: 10.1038/s41598-021-82841-w.

28. Amhaz G, Bazarbachi A, El-Cheikh J. Immunotherapy in indolent non-Hodgkin’s lymphoma. Leuk Res Rep 2022; 17: 100325. doi: 10.1016/j.lrr.2022.100325.

29. Guzauskas GF, Masaquel A, Thuresson PO et al. Obinutuzumab plus chemotherapy followed by obinutuzumab monotherapy is cost-effective vs. rituximab plus chemotherapy followed by rituximab monotherapy for previously untreated follicular lymphoma patients in the United States. Leuk Lymphoma 2019; 60 (7): 1668–1676. doi: 10.1080/10428194.2018.1551532.

30. Tomowiak C, Poulain S, Herbaux C et al. Obinutuzumab and idelalisib in symptomatic patients with relapsed/refractory Waldenström macroglobulinemia. Blood Adv 2021; 5 (9): 2438–2446. doi: 10.1182/bloodadvances.2020003895.

31. Adam Z, Krejčí M, Pour L et al. Obinutuzumab v léčbě pacientky s Waldenströmovou makroglobulinémií netolerující rituximab – popis případu. Trans Hematol Dnes 2021; 27 (2): 160–165. doi: 10.48095/cctahd2021160.

32. Freeman CL, Sehn LH. A tale of two antibodies: obinutuzumab versus rituximab. Br J Haematol 2018; 182 (1): 29–45. doi: 10.1111/bjh.15232.