Twice-weekly induction with ixazomib-lenalidomide-dexamethasone (IRd) combination followed by extended IRd consolidation and lenalidomide maintenance in transplant-eligible patients with newly diagnosed multiple myeloma: Results of the phase 2 study IFM2014-03.
clinical trials
multiple myeloma
transplant
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
29 May 2024
29 May 2024
Historique:
received:
05
01
2024
accepted:
16
05
2024
medline:
30
5
2024
pubmed:
30
5
2024
entrez:
29
5
2024
Statut:
aheadofprint
Résumé
Therapeutic strategies for patients with newly diagnosed multiple myeloma (NDMM) have considerably improved during the last 10 years. The IFM2014-03 trial proposed an all-oral triplet induction/consolidation regimen in transplant-eligible NDMM patients, followed by lenalidomide maintenance. Induction consisted of three 21-day cycles of ixazomib, lenalidomide and dexamethasone (IRd), before high-dose Melphalan with transplant followed by eight 28-day cycles of IRd consolidation before 13 cycles of lenalidomide maintenance. Forty-six patients were enrolled and received at least one dose of therapy, and 39 entered the maintenance phase. The primary end-point was stringent complete response after consolidation, and was achieved in nine patients (20.9%, 90% CI 11.4-33.7; p = 0.998). Ten patients (24.4%) had an undetectable minimal residual disease. The overall response rate was 95.7%. The 3-year progression-free survival was 66.3%. No unexpected toxicities were recorded, and only eight patients suspended from any study drug. Of note, 21 (45.7%) patients reported peripheral neuropathy (PN) (grades 1-2 with no serious adverse events). IRd induction and consolidation with transplant before lenalidomide maintenance shows lower response rates compared to other triplet therapies. It could be an alternative for patients who require an all-oral regimen and/or with pre-existent PN, especially if quadruplet regimens including anti-CD38 antibody are not available.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Bristol-Myers Squibb
Organisme : Takeda Pharmaceutical Company
Organisme : Intergroupe Francophone du Myélome, Paris, France
Informations de copyright
© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
Références
Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med. 1996;335(2):91–97.
Moreau P, Avet‐Loiseau H, Harousseau JL, Attal M. Current trends in autologous stem‐cell transplantation for myeloma in the era of novel therapies. J Clin Oncol. 2011;29(14):1898–1906.
Cavo M, Terpos E, Nanni C, Moreau P, Lentzsch S, Zweegman S, et al. Role of 18F‐FDG PET/CT in the diagnosis and management of multiple myeloma and other plasma cell disorders: a consensus statement by the International Myeloma Working Group. Lancet Oncol. 2017;18(4):e206–e217.
Ladetto M, Pagliano G, Ferrero S, Cavallo F, Drandi D, Santo L, et al. Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol. 2010;28(12):2077–2084.
Terragna C, Zamagni E, Petrucci MY, Patriarca F, Narni F, Crippa C, et al. Molecular remission after bortezomib‐thalidomide‐dexamethasone compared with thalidomide‐dexamethasone as consolidation therapy following double autologous transplantation for multiple myeloma: results of a qualitative and quantitative analysis. Blood. 2010;116(21):861.
Attal M, Lauwers‐Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376:1311–1320.
Kupperman E, Lee EC, Cao Y, Bannerman B, Fitzgerald M, Berger A, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010;70(5):1970–1980.
Kumar SK, Berdeja JG, Niesvizky R, Lonial S, Laubach JP, Hamadani M, et al. Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open‐label phase 1/2 study. Lancet Oncol. 2014;15(13):1503–1512.
Touzeau C, Perrot A, Roussel M, Karlin L, Benboubker L, Jacquet C, et al. All‐oral triplet combination of ixazomib, lenalidomide, and dexamethasone in newly diagnosed transplant‐eligible multiple myeloma patients: final results of the phase II IFM 2013‐06 study. Haematologica. 2022;107(7):1693–1697.
Rajkumar SV. Updated diagnostic criteria and staging system for multiple myeloma. Am Soc Clin Oncol Educ Book. 2016;35:e418–e423.
A'Hern RP. Sample size tables for exact single‐stage phase II designs. Stat Med. 2001;20(6):859–866.
Slade M, Martin TG, Nathwani N, Fiala MA, Rettig MP, Gao F, et al. Ixazomib, lenalidomide and dexamethasone consolidation with randomized ixazomib or lenalidomide maintenance after autologous transplant in newly diagnosed multiple myeloma. Leukemia. 2002;36(12):2917–2921.
Rosinol L, Oriol A, Rios R, et al. Lenalidomide and dexamethasone maintenance with or without ixazomib, tailored by residual disease status in myeloma. Blood. 2023;142(18):1518–1528.
Silvennoinen RH, Waage A, Peceliunas V, Schjesvold F, Anttila P, Säily M, et al. A prospective phase 2 study to assess minimal residual disease after ixazomib, lenalidomide and dexamethasone treatment for newly diagnosed transplant eligible multiple myeloma patients. Blood. 2020;136(Suppl 1):40–41.
Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116(5):679–686.
Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Grishunina M, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non‐inferiority study. Lancet Oncol. 2011;12(5):431–440.
Roussel M, Lauwers‐Cances M, Wuilleme S, Belhadj K, Manier S, Garderet L, et al. Upfront carfilzomib, lenalidomide, and dexamethasone with transplant for patients with multiple myeloma: the IFM KRD final results. Blood. 2021;138(2):113–121.