Skip to main content
Erschienen in:

29.03.2024 | Original Article

Efficacy of daratumumab in newly diagnosed multiple myeloma patients with 1q21 gain

verfasst von: Hirono Iriuchishima, Akio Saito, Masahiro Mihara, Yukie Terasaki, Akira Matsumoto, Atsushi Isoda, Yusuke Furukawa, Morio Matsumoto

Erschienen in: International Journal of Hematology | Ausgabe 1/2024

Einloggen, um Zugang zu erhalten

Abstract

Background

Gain and amplification of 1q21 (1q21+) are adverse chromosomal aberrations of multiple myeloma (MM) that lead to refractoriness to a variety of therapies. While it is known that daratumumab, an anti-cancer monoclonal antibody, cannot overcome the disadvantage of 1q21+in relapsed/refractory MM patients, its benefit in newly diagnosed MM (NDMM) patients with 1q21+has not been clarified.

Patients

We retrospectively evaluated 11 (55%) 1q21+patients (3 copies: 6, > 4 copies: 5) among 20 NDMM patients (median age, 74 years) who received daratumumab-containing regimens at Shibukawa Medical Center from October 2019 to October 2022.

Results

The overall response rate was 82% for patients with 1q21+and 78% for patients without 1q21+. Median progression-free survival (PFS) and median overall survival (OS) were not reached in either group. Neither 1q21 copy number nor co-existence of other high-risk cytogenetic abnormalities significantly affected PFS or OS.

Conclusion

Our preliminary data suggests that outcomes of daratumumab treatment in NDMM 1q21+patients might be non-inferior to those in non-1q21+patients.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat D’Agostino M, Cairns DA, Lahuerta JJ, Wester R, Bertsch U, Waage A, et al. Second revision of the international staging system (r2-iss) for overall survival in multiple myeloma: a european myeloma network (emn) report within the harmony project. J Clin Oncol. 2022;40(29):3406–18.CrossRefPubMed D’Agostino M, Cairns DA, Lahuerta JJ, Wester R, Bertsch U, Waage A, et al. Second revision of the international staging system (r2-iss) for overall survival in multiple myeloma: a european myeloma network (emn) report within the harmony project. J Clin Oncol. 2022;40(29):3406–18.CrossRefPubMed
3.
Zurück zum Zitat Shah GL, Landau H, Londono D, Devlin SM, Kosuri S, Lesokhin AM, et al. Gain of chromosome 1q portends worse prognosis in multiple myeloma despite novel agent-based induction regimens and autologous transplantation. Leuk Lymphoma. 2017;58(8):1823–31.CrossRefPubMedPubMedCentral Shah GL, Landau H, Londono D, Devlin SM, Kosuri S, Lesokhin AM, et al. Gain of chromosome 1q portends worse prognosis in multiple myeloma despite novel agent-based induction regimens and autologous transplantation. Leuk Lymphoma. 2017;58(8):1823–31.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Schmidt TM, Barwick BG, Joseph N, Heffner LT, Hofmeister CC, Bernal L, et al. Gain of Chromosome 1q is associated with early progression in multiple myeloma patients treated with lenalidomide, bortezomib, and dexamethasone. Blood Cancer J. 2019;9(12):94.CrossRefPubMedPubMedCentral Schmidt TM, Barwick BG, Joseph N, Heffner LT, Hofmeister CC, Bernal L, et al. Gain of Chromosome 1q is associated with early progression in multiple myeloma patients treated with lenalidomide, bortezomib, and dexamethasone. Blood Cancer J. 2019;9(12):94.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Abdallah N, Greipp P, Kapoor P, Gertz MA, Dispenzieri A, Baughn LB, et al. Clinical characteristics and treatment outcomes of newly diagnosed multiple myeloma with chromosome 1q abnormalities. Blood Adv. 2020;4(15):3509–19.CrossRefPubMedPubMedCentral Abdallah N, Greipp P, Kapoor P, Gertz MA, Dispenzieri A, Baughn LB, et al. Clinical characteristics and treatment outcomes of newly diagnosed multiple myeloma with chromosome 1q abnormalities. Blood Adv. 2020;4(15):3509–19.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Du C, Mao X, Xu Y, Yan Y, Yuan C, Du X, et al. 1q21 gain but not t(4;14) indicates inferior outcomes in multiple myeloma treated with bortezomib. Leuk Lymphoma. 2020;61(5):1201–10.CrossRefPubMed Du C, Mao X, Xu Y, Yan Y, Yuan C, Du X, et al. 1q21 gain but not t(4;14) indicates inferior outcomes in multiple myeloma treated with bortezomib. Leuk Lymphoma. 2020;61(5):1201–10.CrossRefPubMed
7.
Zurück zum Zitat Hanamura I, Stewart JP, Huang Y, Zhan F, Santra M, Sawyer JR, et al. Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood. 2006;108(5):1724–32.CrossRefPubMedPubMedCentral Hanamura I, Stewart JP, Huang Y, Zhan F, Santra M, Sawyer JR, et al. Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood. 2006;108(5):1724–32.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Dimopoulos MA, Terpos E, Boccadoro M, Delimpasi S, Beksac M, Katodritou E, et al. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(6):801–12.CrossRefPubMed Dimopoulos MA, Terpos E, Boccadoro M, Delimpasi S, Beksac M, Katodritou E, et al. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(6):801–12.CrossRefPubMed
9.
Zurück zum Zitat Bahlis NJ, Dimopoulos MA, White DJ, Benboubker L, Cook G, Leiba M, et al. Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia. 2020;34(7):1875–84.CrossRefPubMedPubMedCentral Bahlis NJ, Dimopoulos MA, White DJ, Benboubker L, Cook G, Leiba M, et al. Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia. 2020;34(7):1875–84.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Weisel K, Spencer A, Lentzsch S, Avet-Loiseau H, Mark TM, Spicka I, et al. Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. J Hematol Oncol. 2020;13(1):115.CrossRefPubMedPubMedCentral Weisel K, Spencer A, Lentzsch S, Avet-Loiseau H, Mark TM, Spicka I, et al. Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. J Hematol Oncol. 2020;13(1):115.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Dimopoulos M, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020;396(10245):186–97.CrossRefPubMed Dimopoulos M, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020;396(10245):186–97.CrossRefPubMed
12.
Zurück zum Zitat Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104–15.CrossRefPubMedPubMedCentral Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104–15.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Mateos MV, Cavo M, Blade J, Dimopoulos MA, Suzuki K, Jakubowiak A, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet. 2020;395(10218):132–41.CrossRefPubMed Mateos MV, Cavo M, Blade J, Dimopoulos MA, Suzuki K, Jakubowiak A, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet. 2020;395(10218):132–41.CrossRefPubMed
14.
Zurück zum Zitat Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394(10192):29–38.CrossRefPubMed Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394(10192):29–38.CrossRefPubMed
15.
Zurück zum Zitat Voorhees PM, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936–45.CrossRefPubMedPubMedCentral Voorhees PM, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936–45.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, et al. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood. 2016;128(7):959–70.CrossRefPubMed Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, et al. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood. 2016;128(7):959–70.CrossRefPubMed
17.
Zurück zum Zitat Mohan M, Weinhold N, Schinke C, Thanedrarajan S, Rasche L, Sawyer JR, et al. Daratumumab in high-risk relapsed/refractory multiple myeloma patients: adverse effect of chromosome 1q21 gain/amplification and GEP70 status on outcome. Br J Haematol. 2020;189(1):67–71.CrossRefPubMed Mohan M, Weinhold N, Schinke C, Thanedrarajan S, Rasche L, Sawyer JR, et al. Daratumumab in high-risk relapsed/refractory multiple myeloma patients: adverse effect of chromosome 1q21 gain/amplification and GEP70 status on outcome. Br J Haematol. 2020;189(1):67–71.CrossRefPubMed
18.
Zurück zum Zitat Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–48.CrossRefPubMed Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–48.CrossRefPubMed
19.
Zurück zum Zitat Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised international staging system for multiple myeloma: a report from international myeloma working group. J Clin Oncol. 2015;33(26):2863–9.CrossRefPubMedPubMedCentral Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised international staging system for multiple myeloma: a report from international myeloma working group. J Clin Oncol. 2015;33(26):2863–9.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Moreau P, Facon T, Usmani S, Bahlis NJ, Raje N, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone (d-rd) versus lenalidomide and dexamethasone (Rd) in transplant-ineligible patients (pts) with newly diagnosed multiple myeloma (ndmm): clinical assessment of key subgroups of the phase 3 maia study. Blood. 2022;140(Supplement 1):7297–300.CrossRef Moreau P, Facon T, Usmani S, Bahlis NJ, Raje N, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone (d-rd) versus lenalidomide and dexamethasone (Rd) in transplant-ineligible patients (pts) with newly diagnosed multiple myeloma (ndmm): clinical assessment of key subgroups of the phase 3 maia study. Blood. 2022;140(Supplement 1):7297–300.CrossRef
21.
Zurück zum Zitat Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378(6):518–28.CrossRefPubMed Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378(6):518–28.CrossRefPubMed
22.
Zurück zum Zitat Facon T, Kumar SK, Plesner T, Orlowski RZ, Moreau P, Bahlis N, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582–96.CrossRefPubMed Facon T, Kumar SK, Plesner T, Orlowski RZ, Moreau P, Bahlis N, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582–96.CrossRefPubMed
23.
Zurück zum Zitat Wang Y, Xu J, Xu B, Li P, Yang Y, Wang W, et al. The prognostic role of 1q21 gain/amplification in newly diagnosed multiple myeloma: the faster, the worse. Cancer. 2023;129(7):1005–16.CrossRefPubMed Wang Y, Xu J, Xu B, Li P, Yang Y, Wang W, et al. The prognostic role of 1q21 gain/amplification in newly diagnosed multiple myeloma: the faster, the worse. Cancer. 2023;129(7):1005–16.CrossRefPubMed
24.
Zurück zum Zitat Hanamura I. Gain/Amplification of chromosome arm 1q21 in multiple myeloma. Cancers (Basel). 2021;13(2):256.CrossRefPubMed Hanamura I. Gain/Amplification of chromosome arm 1q21 in multiple myeloma. Cancers (Basel). 2021;13(2):256.CrossRefPubMed
25.
Zurück zum Zitat Walker BA, Mavrommatis K, Wardell CP, Ashby TC, Bauer M, Davies F, et al. A high-risk, double-hit, group of newly diagnosed myeloma identified by genomic analysis. Leukemia. 2019;33(1):159–70.CrossRefPubMed Walker BA, Mavrommatis K, Wardell CP, Ashby TC, Bauer M, Davies F, et al. A high-risk, double-hit, group of newly diagnosed myeloma identified by genomic analysis. Leukemia. 2019;33(1):159–70.CrossRefPubMed
26.
Zurück zum Zitat Baysal M, Demirci U, Umit E, Kirkizlar HO, Atli EI, Gurkan H, et al. Concepts of double hit and triple hit disease in multiple myeloma, entity and prognostic significance. Sci Rep. 2020;10(1):5991.CrossRefPubMedPubMedCentral Baysal M, Demirci U, Umit E, Kirkizlar HO, Atli EI, Gurkan H, et al. Concepts of double hit and triple hit disease in multiple myeloma, entity and prognostic significance. Sci Rep. 2020;10(1):5991.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DCH, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186(3):1840–8.CrossRefPubMed de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DCH, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186(3):1840–8.CrossRefPubMed
28.
Zurück zum Zitat Overdijk MB, Verploegen S, Bögels M, van Egmond M, Lammerts van Bueren JJ, Mutis T, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015;7(2):311–21.CrossRefPubMedPubMedCentral Overdijk MB, Verploegen S, Bögels M, van Egmond M, Lammerts van Bueren JJ, Mutis T, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015;7(2):311–21.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Ross FM, Avet-Loiseau H, Ameye G, Gutiérrez NC, Liebisch P, O’Connor S, et al. Report from the European Myeloma network on interphase FISH in multiple myeloma and related disorders. Haematologica. 2012;97(8):1272–7.CrossRefPubMedPubMedCentral Ross FM, Avet-Loiseau H, Ameye G, Gutiérrez NC, Liebisch P, O’Connor S, et al. Report from the European Myeloma network on interphase FISH in multiple myeloma and related disorders. Haematologica. 2012;97(8):1272–7.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Gao L, Liu Y, Li Y, Feng L, Wang Z, Wen L, et al. The importance of fish signal cut-off value and copy number variation for 1q21 in newly diagnosed multiple myeloma: is it underestimated? Clin Lymphoma Myeloma Leuk. 2022;22(7):535–44.CrossRefPubMed Gao L, Liu Y, Li Y, Feng L, Wang Z, Wen L, et al. The importance of fish signal cut-off value and copy number variation for 1q21 in newly diagnosed multiple myeloma: is it underestimated? Clin Lymphoma Myeloma Leuk. 2022;22(7):535–44.CrossRefPubMed
Metadaten
Titel
Efficacy of daratumumab in newly diagnosed multiple myeloma patients with 1q21 gain
verfasst von
Hirono Iriuchishima
Akio Saito
Masahiro Mihara
Yukie Terasaki
Akira Matsumoto
Atsushi Isoda
Yusuke Furukawa
Morio Matsumoto
Publikationsdatum
29.03.2024
Verlag
Springer Nature Singapore
Erschienen in
International Journal of Hematology / Ausgabe 1/2024
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-024-03760-w

Neu im Fachgebiet Onkologie

KI-gestütztes Mammografiescreening überzeugt im Praxistest

Mit dem Einsatz künstlicher Intelligenz lässt sich die Detektionsrate im Mammografiescreening offenbar deutlich steigern. Mehr unnötige Zusatzuntersuchungen sind laut der Studie aus Deutschland nicht zu befürchten.

Welche Krebserkrankungen bei Zöliakie häufiger auftreten

Eine große Kohortenstudie hat den Zusammenhang zwischen Zöliakie und gastrointestinalen Krebserkrankungen und inflammatorischen Krankheiten untersucht. Neben gastrointestinalen Tumoren ist auch ein nicht solider Krebs häufiger.

Adjuvanter PD-L1-Hemmer verhindert Rezidive bei Hochrisiko-Urothelkarzinom

Sind Menschen mit muskelinvasivem Urothelkarzinom für die neoadjuvante platinbasierte Therapie nicht geeignet oder sprechen sie darauf nicht gut an, ist Pembrolizumab eine adjuvante Alternative: Die krankheitsfreie Lebenszeit wird dadurch mehr als verdoppelt.

Duale Checkpointhemmung gegen Melanome verlängert langfristig das Leben

Im Vergleich zu den Überlebenschancen vor der Einführung von Immuncheckpointhemmern (ICI) ist der Fortschritt durch eine ICI-Kombination mit unterschiedlichen Tagets bei fortgeschrittenem Melanom erstaunlich. Das belegen die finalen Ergebnisse der CheckMate-067-Studie und geben Betroffenen "Hoffnung auf Heilung".

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.