29 september 2022: Bron:  BLOOD 2022

Het toevoegen van daratumumab aan een VCd-kuur (bortezomib, cyclofosfamide en dexamethason) bij patiënten met light chain Amyloïdose verhoogt het percentage diepe hematologische responsen en meer patiënten bereiken een zeer goede partiële respons in vergelijking met patiënten die alleen een VCd-kuur krijgen. Dat blijkt uit de resultaten van de fase III ANDROMEDA  studie.

Deze ziekte is verwant aan Multiple Myeloma (ziekte van Kahler - botkanker of beenmergkanker) en ziekte van Waldenström.  Zie ook kwaadaardige plasmacelziekten

De onderzoekers hebben gerandomiseerd 388 patiënten ingedeeld in twee groepen. 1 groep kreeg alleen een VCd-kuur (bortezomibcyclofosfamide en dexamethason). De andere groep kreeg daaraan toegevoegd daratumumab.  

  • Patiënten kregen wekelijks bortezomib (1,3 mg/m²), cyclofosfamide (300 mg/m² tot 500 mg per week) en dexamethason (20 tot 40 mg) toegediend gedurende zes cycli van 28 dagen.
  • De studiegroep kreeg ook subcutaan daratumumab (in de vorm van 1.800 mg samen met recombinant humaan hyaluronidase PH20 in 15 ml) eenmaal per week in cycli 1 en 2 en elke twee weken in cycli 3 tot en met 6.
  • Na cyclus 6 kreeg de D-VCd groep elke vier weken alleen subcutaan daratumumab, tot een totaal van 24 cycli vanaf de eerste dosis.
  • Bovendien kregen in de D-VCd-groep 149 patiënten (77,2 procent) na zes cycli alleen daratumumab; van die patiënten hadden 17 (11,4 procent) een doorlopende behandeling.

Het primaire einddoel was het totale hematologische complete responspercentage.
Secundaire einddoelen waren onder meer progressievrije respons, orgaanrespons, tijd tot hematologische respons, algehele overleving en veiligheid.
De mediane duur van de behandeling was 21,3 maanden voor D-VCd en 5,3 maanden voor VCd.

De mate van diepe hematologische responsen was beter en effectiever voor D-VCd en meer patiënten bereikten een zeer goede partiële respons ten opzichte van alleen VCd.
Specifiek, na 18 maanden, vonden de onderzoekers significant grotere percentages aan hartresponses (53 versus 24 procent) en nierresponspercentages (58 versus 26 procent) met D-VCd versus VC-d.

Het abstract van de studie werd gepubliceerd op BLOOD 2022. Voor een volledige studierapport moet betaald worden:


In the phase 3 ANDROMEDA trial, patients treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) had significantly higher rates of organ and hematologic response compared with patients who received VCd alone. Here, we present patient-reported outcomes (PROs) from the ANDROMEDA trial. PROs were assessed through cycle 6 using three standardized questionnaires. Treatment effect through cycle 6 was measured by a repeated-measures, mixed-effects model. The magnitude of changes in PROs versus baseline was generally low, but between-group differences favored the D-VCd group. Results were generally consistent irrespective of hematologic, cardiac, or renal responses. More patients in the D-VCd group experienced meaningful improvements in PROs; median time to improvement was more rapid in the D-VCd group versus the VCd group. After cycle 6, patients in the D-VCd group received daratumumab monotherapy and their PRO assessments continued, with improvements in health-related quality of life (HRQoL) reported through cycle 19. PROs of subgroups with renal and cardiac involvement were consistent with those of the intent-to-treat population. These results demonstrate that the previously reported clinical benefits of D-VCd were achieved without decrement to patients' HRQoL and provide support of D-VCd in patients with AL amyloidosis.

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    1. Dittrich T, Kimmich C, Hegenbart U, Schonland SO. Prognosis and staging of AL amyloidosis. Acta Haematol. 2020;143(4):388-400.
    1. Lin HM, Seldin D, Hui AM, Berg D, Dietrich CN, Flood E. The patient's perspective on the symptom and everyday life impact of AL amyloidosis. Amyloid. 2015;22(4):244-251.
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    1. Palladini G, Schonland S, Merlini G, et al. First glimpse on real-world efficacy outcomes for 2000 patients with systemic light chain amyloidosis in europe: a retrospective observational multicenter study by the european myeloma network. Blood. 2020;136(Supplement 1):50-51. https://doi.org/10.1182/blood-2020-140708
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    1. Warsame R, Kumar SK, Gertz MA, et al. Hematology patient reported symptom screen to assess quality of life for AL amyloidosis. Am J Hematol. 2017;92(5):435-440.
    1. Chakraborty R, Rybicki L, Tomer J, et al. Patient-reported outcomes in systemic AL amyloidosis with functional assessment of cancer therapy-general (FACT-G) and patient-reported outcomes measurement information system-global health (PROMIS-GH) in a real-world population. Leuk Lymphoma. 2019;60(14):3544-3551.
    1. Wright NL, Flynn KE, Brazauskas R, Hari P, D'Souza A. Patient-reported distress is prevalent in systemic light chain (AL) amyloidosis but not determined by severity of disease. Amyloid. 2018;25(2):129-134.
    1. Seldin DC, Anderson JJ, Sanchorawala V, et al. Improvement in quality of life of patients with AL amyloidosis treated with high-dose melphalan and autologous stem cell transplantation. Blood. 2004;104(6):1888-1893.
    1. Lousada I, Comenzo RL, Landau H, Guthrie S, Merlini G. Light chain amyloidosis: patient experience survey from the amyloidosis research consortium. Adv Ther. 2015;32(10):920-928.
    1. Rizio AA, White MK, McCausland KL, et al. Treatment tolerability in patients with immunoglobulin light-chain amyloidosis. Am Health Drug Benefits. 2018;11(8):430-437.
    1. Bayliss M, McCausland KL, Guthrie SD, White MK. The burden of amyloid light chain amyloidosis on health-related quality of life. Orphanet J Rare Dis. 2017;12(1):15.
    1. Mahmood S, Palladini G, Sanchorawala V, Wechalekar A. Update on treatment of light chain amyloidosis. Haematologica. 2014;99(2):209-221.
    1. Jaccard A, Comenzo RL, Hari P, et al. Efficacy of bortezomib, cyclophosphamide and dexamethasone in treatment-naive patients with high-risk cardiac AL amyloidosis (Mayo Clinic stage III). Haematologica. 2014;99(9):1479-1485. https://doi.org/10.3324/haematol.2014.104109
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    1. Mikhael JR, Schuster SR, Jimenez-Zepeda VH, et al. Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood. 2012;119(19):4391-4394.
    1. Gavriatopoulou M, Musto P, Caers J, et al. European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias. Leukemia. 2018;32(9):1883-1898.
    1. Weber N, Mollee P, Augustson B, et al. Management of systemic AL amyloidosis: recommendations of the Myeloma Foundation of Australia Medical and Scientific Advisory Group. Intern Med J. 2015;45(4):371-382.
    1. Wechalekar AD, Gillmore JD, Bird J, et al. Guidelines on the management of AL amyloidosis. Br J Haematol. 2015;168(2):186-206.
    1. Schutz N, Nucifora E, Fantl D, et al. AL amyloidosis: real world evidence from Argentina. Paper presented at the 21st Congress of the European Hematology Association; 2016. https://library.ehaweb.org/eha/2017/22nd/181040/natalia.schutz.frailty.a...
    1. Dispenzieri A, Zonder J, Hoffman J, et al. Real-world treatment patterns in patients with light chain (al) amyloidosis: Analysis of the optum us electronic health records and commercial claims database. Blood. 2020;136(Supplement 1):4-5. https://doi.org/10.1182/blood-2020-140405
    1. Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-based treatment for immunoglobulin light chain amyloidosis. N Engl J Med. 2021;385(1):46-58.
    1. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473-483.
    1. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365-376.
    1. Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727-1736.
    1. Ware JE Jr, Kosinski M, Keller SD. SF-36 Physical and Mental Health Summary Scales: A User's Manual. Health Assessment Lab, New England Medical Center; 1994.
    1. White MK, Bayliss MS, Guthrie SD, Raymond KP, Rizio AA, McCausland KL. Content validation of the SF-36v2(R) health survey with AL amyloidosis patients. J Patient Rep Outcomes. 2017;1(1):13.
    1. White MK, McCausland KL, Sanchorawala V, Guthrie SD, Bayliss MS. Psychometric validation of the SF-36 health survey in light chain amyloidosis: results from community-based and clinic-based samples. Patient Relat Outcome Meas. 2017;8:157-167.
    1. Kvam AK, Fayers PM, Wisloff F. Responsiveness and minimal important score differences in quality-of-life questionnaires: a comparison of the EORTC QLQ-C30 cancer-specific questionnaire to the generic utility questionnaires EQ-5D and 15D in patients with multiple myeloma. Eur J Haematol. 2011;87(4):330-337.
    1. Pickard AS, Neary MP, Cella D. Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer. Health Qual Life Outcomes. 2007;5:70.
    1. McDowell I. Measuring Health: a Guide to Rating Scales and Questionnaires. 3rd ed. Oxford University Press; 2006. https://doi.org/10.1093/acprof:oso/9780195165678.001.0001
    1. Nolte S, Liegl G, Petersen MA, et al. General population normative data for the EORTC QLQ-C30 health-related quality of life questionnaire based on 15 386 persons across 13 European countries, Canada and the United States. Eur J Cancer. 2019;107:153-163.
    1. Scott NW, Fayers PM, Aaronson NK, et al. EORTC QLQ-C30 reference values 2008. 2008. https://www.eortc.org/app/uploads/sites/2/2018/02/reference_values_manua....
    1. Sanchorawala V, Palladini G, Kukreti V, et al. A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis. Blood. 2017;130(5):597-605.
    1. Caccialanza R, Palladini G, Klersy C, et al. Nutritional status independently affects quality of life of patients with systemic immunoglobulin light-chain (AL) amyloidosis. Ann Hematol. 2012;91(3):399-406.
    1. Kaufman GP, Dispenzieri A, Gertz MA, et al. Kinetics of organ response and survival following normalization of the serum free light chain ratio in AL amyloidosis. Am J Hematol. 2015;90(3):181-186.
    1. Szalat R, Sarosiek S, Havasi A, Brauneis D, Sloan JM, Sanchorawala V. Organ responses after highdose melphalan and stemcell transplantation in AL amyloidosis. Leukemia. 2021;35(3):916-919.
    1. Gertz MA. Immunoglobulin light chain amyloidosis: 2020 update on diagnosis, prognosis, and treatment. Am J Hematol. 2020;95(7):848-860.
    1. Milani P, Palladini G. Conventional therapy for amyloid light-chain amyloidosis. Acta Haematol. 2020;143(4):365-372.
    1. Sarosiek S, Zheng L, Sloan JM, Quillen K, Brauneis D, Sanchorawala V. Comparing measures of hematologic response after high-dose melphalan and stem cell transplantation in AL amyloidosis. Blood Cancer J. 2020;10(8):88.
    1. Jaccard A, Moreau P, Leblond V, et al. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2007;357(11):1083-1093.
    1. D'Souza A, Huang J, Hari P. New light chain amyloid response criteria help risk stratification of patients by day 100 after autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22(4):768-770.
    1. Minnema MC, Nasserinejad K, Hazenberg B, et al. Bortezomib-based induction followed by stem cell transplantation in light chain amyloidosis: results of the multicenter HOVON 104 trial. Haematologica. 2019;104(11):2274-2282.
    1. Sanchorawala V, Sun F, Quillen K, Sloan JM, Berk JL, Seldin DC. Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation: 20-year experience. Blood. 2015;126(20):2345-2347.
    1. Mollee PN, Wechalekar AD, Pereira DL, et al. Autologous stem cell transplantation in primary systemic amyloidosis: the impact of selection criteria on outcome. Bone Marrow Transplant. 2004;33(3):271-277.
    1. Dispenzieri A, Kyle RA, Lacy MQ, et al. Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood. 2004;104(6):1881-1887. http://dx.doi.org/10.1182/blood-2004-01-0390
    1. Skinner M, Sanchorawala V, Seldin DC, et al. High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med. 2004;140(2):85-93.

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