%0 Journal Article
%A Seckinger, Anja
%A Salwender, Hans
%A Martin, Hans
%A Scheid, Christof
%A Hielscher, Thomas
%A Bertsch, Uta
%A Hummel, Manuela
%A Jauch, Anna
%A Knauf, Wolfgang
%A Emde-Rajaratnam, Martina
%A Beck, Susanne
%A Neben, Kai
%A Dührig, Jan
%A Lindemann, Walter
%A Schmidt-Wolf, Ingo G H
%A Hänel, Mathias
%A Blau, Igor W
%A Weisel, Katja
%A Weinhold, Niels
%A Raab, Marc S
%A Goldschmidt, Hartmut
%A Choon-Quinones, Mimi
%A Hose, Dirk
%T Molecular Long-Term Analysis of the GMMG-HD4 Trial in Multiple Myeloma-Patterns of Association of Chromosomal Aberrations with Response and Proliferation Determining Survival in Selecting Treatments in View of Limited Resources in Low- and Middle-Income Countries.
%J International journal of molecular sciences
%V 25
%N 12
%@ 1422-0067
%C Basel
%I Molecular Diversity Preservation International
%M DKFZ-2024-01385
%P 6431
%D 2024
%X Based on the lack of differences in progression-free and overall survival after a median follow-up of 93 months in our HOVON-65/GMMG-HD4 trial (German part; n = 395) randomizing VAD induction (vincristin/adriamycin/dexamthasone)/tandem-transplantation/thalidomide-maintenance vs. PAD induction (bortezomib/adriamycin/dexamethasone)/tandem transplantation/bortezomib maintenance, we discern how chromosomal aberrations determine long-term prognosis by different patterns of association with proliferation and treatment-dependent response, whether responses achieved by different regimens are equal regarding prognosis, and whether subpopulations of patients could be defined as treatable without upfront 'novel agents' in cases of limited resources, e.g., in low- or middle-income countries. Serum parameters and risk factors were assessed in 395 patients. CD138-purified plasma cells were subjected to fluorescence in situ hybridization (n = 354) and gene expression profiling (n = 204). We found chromosomal aberrations to be associated in four patterns with survival, proliferation, and response: deletion (del) del17p13, del8p21, del13q14, (gain) 1q21+, and translocation t(4;14) (all adverse) associate with higher proliferation. Of these, del17p is associated with an adverse response (pattern 1), and 1q21+, t(4;14), and del13q14 with a treatment-dependent better response (pattern 2). Hyperdiploidy associates with lower proliferation without impacting response or survival (pattern 3). Translocation t(11;14) has no association with survival but a treatment-dependent adverse response (pattern 4). Significantly fewer patients reach a near-complete response or better with 'conventional' (VAD) vs. bortezomib-based treatment after induction or high-dose melphalan. These patients, however, show significantly better median progression-free and overall survival. Molecularly, patients responding to the two regimens differ in gene expression, indicating distinct biological properties of the responding myeloma cells. Patients with normal renal function (89.4
%K Humans
%K Multiple Myeloma: genetics
%K Multiple Myeloma: drug therapy
%K Multiple Myeloma: mortality
%K Multiple Myeloma: pathology
%K Chromosome Aberrations
%K Female
%K Male
%K Middle Aged
%K Aged
%K Antineoplastic Combined Chemotherapy Protocols: therapeutic use
%K Cell Proliferation: drug effects
%K Prognosis
%K Adult
%K Developing Countries
%K Dexamethasone: therapeutic use
%K Dexamethasone: pharmacology
%K Bortezomib: therapeutic use
%K Bortezomib: pharmacology
%K Thalidomide: therapeutic use
%K LMIC (Other)
%K molecular profiling (Other)
%K multiple myeloma (Other)
%K proliferation (Other)
%K response (Other)
%K survival (Other)
%K Dexamethasone (NLM Chemicals)
%K Bortezomib (NLM Chemicals)
%K Thalidomide (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38928138
%2 pmc:PMC11204152
%R 10.3390/ijms25126431
%U https://inrepo02.dkfz.de/record/291411