Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Mar 10;2(2):100092.
doi: 10.1016/j.bneo.2025.100092. eCollection 2025 May.

Improved survival with daratumumab-CyBorD compared with CyBorD as frontline therapy for AL amyloidosis

Binoy Yohannan  1 , Matthew Rees  1 , Morie A Gertz  1 , Angela Dispenzieri  1 , Prashant Kapoor  1 , Francis K Buadi  1 , David Dingli  1 , Nelson Leung  1 , Martha Q Lacy  1 , Suzanne R Hayman  1 , Wilson Gonsalves  1 , Taxiarchis Kourelis  1 , Joselle Cook  1 , Moritz Binder  1 , Mustaqeem Siddiqui  1 , Yi Lin  1 , Lisa Hwa  1 , Michelle G Rogers  1 , Miriam Hobbs  1 , Amie Fonder  1 , Rahma Warsame  1 , S Vincent Rajkumar  1 , Shaji K Kumar  1 , Eli Muchtar  1
Affiliations
Clinical Trial

Improved survival with daratumumab-CyBorD compared with CyBorD as frontline therapy for AL amyloidosis

Binoy Yohannan et al. Blood Neoplasia. .

Abstract

In the ANDROMEDA phase 3 trial, the addition of daratumumab to cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as frontline therapy significantly improved hematological and organ responses, and event-free survival (EFS) compared with CyBorD. To validate its results, we performed a retrospective study of 361 consecutive patients with newly diagnosed light chain (AL) amyloidosis treated between 2018 and 2022. Patients who received Dara-CyBorD (n = 147) were compared with those treated with CyBorD (n = 214) in key outcome endpoints. The 2-month hematological very good partial response or better rate was higher with Dara-CyBorD than with CyBorD (60.8% vs 31.1%; P < .001). In addition, 2- and 6-month hematological complete response was also higher with Dara-CyBorD (15.3% vs 3.0% and 39.5% vs 17.8%, respectively; both P < .001). Fewer patients treated with Dara-CyBorD required second-line therapy at the 12-month landmark (14.9% vs 42.9%; P < .001). The 6- and 12-month cardiac responses were higher and deeper in the Dara-CyBorD group than in the CyBorD group. Dara-CyBorD was associated with a lower 6-month mortality rate (8.8% vs 16.3%; P = .04) and superior EFS and overall survival (OS). An OS difference between the treatment groups was statistically significant among patients with stage II cardiac disease, and borderline significant for stage IIIA but not for cardiac stage IIIB. In conclusion, the addition of daratumumab to frontline CyBorD significantly improved hematological and organ response rates, reduced early deaths, and prolonged EFS and OS compared with CyBorD.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: M.A.G. reports honoraria from Celgene, Med Learning Group, Research to Practice, Prothena, Apellis Pharmaceuticals, Amgen, AbbVie, Akcea Therapeutics, Sanofi, Telix Pharmaceuticals, Janssen Oncology, Juno/Celgene, and Alnylam; reports a consulting or advisory role with Prothena and Bristol Myers Squibb/Sanofi; and reports travel, accommodations, and expenses from Prothena, Celgene, and Novartis. A.D. reports a consulting or advisory role with Janssen Research and Development; reports research funding from 10.13039/100006436Celgene (institutional), 10.13039/100005565Janssen Oncology (institutional), 10.13039/100004319Pfizer (institutional), 10.13039/100007723Takeda (institutional), 10.13039/100006400Alnylam (institutional), and Prothena; and reports travel, accommodations, and expenses from Pfizer, Janssen Oncology, and Prothena. P.K. reports honoraria from Pharmacyclics, Sanofi (institutional), BeiGene, MustangBio, AstraZeneca, and AbbVie (institutional); reports consulting or advisory role with Sanofi (institutional); and received research funding from 10.13039/100002429Amgen (institutional), 10.13039/100007723Takeda (institutional), 10.13039/100004339Sanofi (institutional), 10.13039/100006483AbbVie (institutional), 10.13039/100004330GlaxoSmithKline (institutional), Sorrento Therapeutics (institutional), 10.13039/100007136Karyopharm Therapeutics (institutional), 10.13039/100009857Regeneron (institutional), Ichnos Sciences (institutional), 10.13039/100002491Bristol Myers Squibb/10.13039/100006436Celgene (institutional). D.D. reports a consulting role for Alexion (AstraZeneca), Apellis, Bristol Myers Squibb, Genentech/Roche, Janssen, Legend Biotech, Novartis, Ossium Health, Sanofi, and Sorrento Therapeutics; and reports research support from K36 Therapeutics. N.L. reports membership on an entity’s board of directors or advisory committees with Takeda. M.Q.L. reports research funding from 10.13039/100006436Celgene. W.G. reports consulting or an advisory role with Amgen (institutional); reports research funding from 10.13039/501100022241ORIC Pharmaceuticals (institutional) and 10.13039/100001009Bristol Myers Squibb Foundation (institutional); and reports patents, royalties, other intellectual property, with patent number: 10996224 (Assessing and treating precursor plasma cell disorders). T.K. reports research funding from 10.13039/100004336Novartis. J.C. reports stock and other ownership interests in Geron. Y.L. reports consultancy with, and research funding from bluebird bio, 10.13039/100006436Celgene, 10.13039/100005565Janssen, and Kite; reports consultancy with Gamida Cell, 10.13039/100004336Novartis, Juno, Legend, Sorrento, and Vineti; reports research funding from 10.13039/100004334Merck, 10.13039/100007723Takeda, Kite, 10.13039/100004334Merck, 10.13039/100004336Novartis, 10.13039/100004337Roche, and 10.13039/100004339Sanofi; reports membership on an entity’s board of directors or advisory committees with AbbVie, 10.13039/100006436Celgene, 10.13039/100005565Janssen, 10.13039/100007723Takeda, Adaptive, 10.13039/501100004628MedImmune/AstraZeneca; and reports a role on an independent review committee for Oncopeptides. S.V.R. reports honoraria from Research To Practice and Medscape; and receives authorship royalties from Up To Date. S.K.K. reports consulting or advisory role with Takeda (institutional), Janssen Oncology (institutional), Genentech/Roche (institutional), AbbVie (institutional), Bristol Myers Squibb/Celgene (institutional), Pfizer (institutional), Regeneron (institutional), Sanofi (institutional), and K36 (institutional); reports research funding from 10.13039/100007723Takeda (institutional), 10.13039/100006483AbbVie (institutional), 10.13039/100004336Novartis (institutional), 10.13039/100004339Sanofi (institutional), 10.13039/100005565Janssen Oncology (institutional), 10.13039/501100004628MedImmune (institutional), 10.13039/100004337Roche/10.13039/100004328Genentech (institutional), CARsgen Therapeutics (institutional), 10.13039/100024192Allogene Therapeutics (institutional), 10.13039/100004330GlaxoSmithKline (institutional), 10.13039/100009857Regeneron (institutional), and 10.13039/100002491Bristol Myers Squibb/10.13039/100006436Celgene (institutional); and reports travel, accommodations, and expenses from AbbVie and Pfizer. E.M. reports consultation fee from Protego (fee paid to the institution). The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
CONSORT diagram of patient selection and treatment groups.
Figure 2.
Figure 2.
Hematological and organ responses at designated landmarks. (A) Hematological response. (B) Cardiac response. (C) Renal response.
Figure 3.
Figure 3.
Survival outcomes by treatment group. (A) EFS comparing Dara-CyBorD vs CyBorD (2-year EFS, 65.2% vs 25.9%; HR, 0.36; 95% CI, 0.27-0.47; P < .001). (B) OS comparing Dara-CyBorD vs CyBorD (2-year OS, 82.0% vs 69.6%; HR, 0.53; 95% CI, 0.36-0.79; P = .003). (C) OS comparing Dara-CyBorD vs frontline CyBorD with subsequent use of Dara vs frontline CyBorD without subsequent Dara use (2-year OS, 82.0% vs 84.6% vs 53.4% [P < .001]; Dara-CyBorD vs CyBorD with subsequent Dara use [P = .96]; Dara-CyBorD vs frontline CyBorD without subsequent Dara use [P < .001]; frontline CyBorD with subsequent use of Dara vs frontline CyBorD without subsequent Dara use [P < .001]).
Figure 4.
Figure 4.
EFS based on cardiac stage stratified by treatment group. (A) Cardiac stage I (2-year EFS, 80% vs 30 %; HR, 0.22; 95% CI, 0.10-0.46; P < .001). (B) Cardia stage II (2-year EFS, 77.1% vs 37.1%; HR, 0.29; 95% CI, 0.17-0.48; P < .001). (C) Cardiac stage IIIA (2-year EFS, 62.2% % vs 22.2%; HR, 0.34; 95% CI, 0.21-0.56; P < .001). (D) Cardiac stage IIIB (2-year EFS, 12.5% vs 9.3%; HR, 0.89; 95% CI, 0.48-1.66; P = .72).
Figure 5.
Figure 5.
OS based on cardiac stage stratified by treatment group. (A) Cardiac stage I (2-year OS, 100% vs 96.5%; HR, 0.14; 95% CI, 0.004-4.11; P = .25). (B) Cardiac stage II (2-year OS, 97.6 % vs 78.9%; HR, 0.10; 95% CI, 0.04-0.24; P = .004). (C) Cardiac stage IIIA (2-year OS, 76.9 % vs 61.9%; HR, 0.57; 95% CI, 0.30-1.10; P = .12). (D) Cardiac stage IIIB (2-year OS, 15.6% vs 40.6%; HR, 1.25; 95% CI, 0.62-2.53; P = .48).
See this image and copyright information in PMC

References

    1. Merlini G, Dispenzieri A, Sanchorawala V, et al. Systemic immunoglobulin light chain amyloidosis. Nat Rev Dis Primers. 2018;4(1):38. - PubMed
    1. Weiss BM, Hebreo J, Cordaro DV, et al. Increased serum free light chains precede the presentation of immunoglobulin light chain amyloidosis. J Clin Oncol. 2014;32(25):2699–2704. - PMC - PubMed
    1. Kastritis E, Fotiou D, Theodorakakou F, et al. Timing and impact of a deep response in the outcome of patients with systemic light chain (AL) amyloidosis. Amyloid. 2021;28(1):3–11. - PubMed
    1. Staron A, Zheng L, Doros G, et al. Marked progress in AL amyloidosis survival: a 40-year longitudinal natural history study. Blood Cancer J. 2021;11(8):139. - PMC - PubMed
    1. Muchtar E, Gertz MA, Kumar SK, et al. Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death. Blood. 2017;129(15):2111–2119. - PMC - PubMed

Publication types

LinkOut - more resources