Zanubrutinib Plus BR in Newly Diagnosed Symptomatic WM

Summary

This study aims to evaluate the long-term efficacy of BTK inhibitor Zanubrutinib combined bendamustine and rituximab (ZBR) for time-limited treatment of Waldenstrom macroglobulinemia, The combination therapy is expected to improve the remission depth, prolong the remission time, and improve the progression-free survival and overall survival of newly diagnosed WM patients. On the one hand, the patients have to bear a long-term economic burden, which is often difficult for some patients to adhere to for a long time. On the other hand, in the course of long-term treatment of BTKi, drug resistance and intolerable side effects are prone to occur. At the same time, it can prevent the disease rebound after the withdrawal of BTKi, so as to achieve the phased withdrawal of WM

Timeline

Start

2023-02-15

Primary completion

2025-03-15

Completion

2025-12-15

Publications

• Background Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grunhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Durk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; Study group indolent Lymphomas (StiL). 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 Apr 6;381(9873):1203-10. doi: 10.1016/S0140-6736(12)61763-2. Epub 2013 Feb 20.
• Background Dimopoulos MA, Garcia-Sanz R, Gavriatopoulou M, Morel P, Kyrtsonis MC, Michalis E, Kartasis Z, Leleu X, Palladini G, Tedeschi A, Gika D, Merlini G, Kastritis E, Sonneveld P. 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 Nov 7;122(19):3276-82. doi: 10.1182/blood-2013-05-503862. Epub 2013 Sep 4.
• Background Castillo JJ, Meid K, Gustine JN, Leventoff C, White T, Flynn CA, Sarosiek S, Demos MG, Guerrera ML, Kofides A, Liu X, Munshi M, Tsakmaklis N, Xu L, Yang G, Branagan AR, O'Donnell E, Raje N, Yee AJ, Patterson CJ, Hunter ZR, Treon SP. Long-term follow-up of ibrutinib monotherapy in treatment-naive patients with Waldenstrom macroglobulinemia. Leukemia. 2022 Feb;36(2):532-539. doi: 10.1038/s41375-021-01417-9. Epub 2021 Sep 16.
• Background Dimopoulos MA, Tedeschi A, Trotman J, Garcia-Sanz R, Macdonald D, Leblond V, Mahe B, Herbaux C, Tam C, Orsucci L, Palomba ML, Matous JV, Shustik C, Kastritis E, Treon SP, Li J, Salman Z, Graef T, Buske C; iNNOVATE Study Group and the European Consortium for Waldenstrom's Macroglobulinemia. Phase 3 Trial of Ibrutinib plus Rituximab in Waldenstrom's Macroglobulinemia. N Engl J Med. 2018 Jun 21;378(25):2399-2410. doi: 10.1056/NEJMoa1802917. Epub 2018 Jun 1.
• Background Trotman J, Opat S, Gottlieb D, Simpson D, Marlton P, Cull G, Munoz J, Tedeschi A, Roberts AW, Seymour JF, Atwal SK, Yu Y, Novotny W, Holmgren E, Tan Z, Hilger JD, Huang J, Tam CS. Zanubrutinib for the treatment of patients with Waldenstrom macroglobulinemia: 3 years of follow-up. Blood. 2020 Oct 29;136(18):2027-2037. doi: 10.1182/blood.2020006449.
• Background Kastritis E, Gavriatopoulou M, Kyrtsonis MC, Roussou M, Hadjiharissi E, Symeonidis A, Repoussis P, Michalis E, Delimpasi S, Tsatalas K, Tsirigotis P, Vassou A, Vervessou E, Katodritou E, Gika D, Terpos E, Dimopoulos MA. Dexamethasone, rituximab, and cyclophosphamide as primary treatment of Waldenstrom macroglobulinemia: final analysis of a phase 2 study. Blood. 2015 Sep 10;126(11):1392-4. doi: 10.1182/blood-2015-05-647420. No abstract available.
• Background Treon SP, Soumerai JD, Branagan AR, Hunter ZR, Patterson CJ, Ioakimidis L, Chu L, Musto P, Baron AD, Nunnink JC, Kash JJ, Terjanian TO, Hyman PM, Nawfel EL, Sharon DJ, Munshi NC, Anderson KC. Lenalidomide and rituximab in Waldenstrom's macroglobulinemia. Clin Cancer Res. 2009 Jan 1;15(1):355-60. doi: 10.1158/1078-0432.CCR-08-0862.
• Background Paludo J, Abeykoon JP, Shreders A, Ansell SM, Kumar S, Ailawadhi S, King RL, Koehler AB, Reeder CB, Buadi FK, Dispenzieri A, Lacy MQ, Dingli D, Witzig TE, Go RS, Gonsalves WI, Kourelis T, Warsame R, Leung N, Habermann TM, Hayman S, Lin Y, Kyle RA, Rajkumar SV, Gertz MA, Kapoor P. Bendamustine and rituximab (BR) versus dexamethasone, rituximab, and cyclophosphamide (DRC) in patients with Waldenstrom macroglobulinemia. Ann Hematol. 2018 Aug;97(8):1417-1425. doi: 10.1007/s00277-018-3311-z. Epub 2018 Apr 3.
• Background Castillo JJ, Abeykoon JP, Gustine JN, Zanwar S, Mein K, Flynn CA, Demos MG, Guerrera ML, Kofides A, Liu X, Munshi M, Tsakmaklis N, King R, Yang G, Hunter ZR, Advani RH, Palomba ML, Ansell SM, Gertz MA, Kapoor P, Treon SP. Partial response or better at six months is prognostic of superior progression-free survival in Waldenstrom macroglobulinaemia patients treated with ibrutinib. Br J Haematol. 2021 Feb;192(3):542-550. doi: 10.1111/bjh.17225. Epub 2020 Nov 18.
• Background 2020 EHA EP1194
• Background 2021 ASCO 8049

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