EGAGenomicsCancer Genomicshttps://ega-archive.org/studies/EGAS00001006342EGAEGA study EGAS00001006342Molecular determinants of outcomes in relapsed mantle cell lymphoma treated with ibrutinib or temsirolimus in the MCL3001 (RAY) trialEGArestrictedMantle-Zone Lymphoma, mantle cell, Imbruvica, Centrocytic Small Cell, Mantle-Cell Lymphoma, PCI-32765, CCI 779, RAY, Centrocytic, rapamycin 42-(2, Intermediate, PCI32765, AU040256, H-ray, ray, 1-((3R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo(3, Intermediate Differentiated, Lymphomas, Raja trachyderma., Mantle-Cell, Lymphocytic, CCI-779, RAB1C, Mantle-Zone, Small-Cell Lymphomas, Centrocytic Small-Cell, Small-Cell Lymphoma, 2-bis(hydroxymethyl)propionate), Diffuse, Small-Cell, Mantle Cell, Torisel, lymphoma, 4-d)pyrimidin-1-yl)piperidin-1- yl)prop-2-en-1-one, Lymphocytic Lymphoma, Centrocytic Small-Cell Lymphomas, Poorly-Differentiated, Mantle-Zone Lymphomas, Lymphoma, Mantle Zone Lymphoma, Centrocytic Small-Cell Lymphoma, Mantle-Cell Lymphomas, PCI 32765, Diffuse Lymphocytic Lymphoma, Poorly Differentiated, 42-(3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate), Mantle Cell Lymphoma, 9530019H02Rik, rapamycinMantle-Zone Lymphoma, mantle cell, l(1)G0410, Ribonucleic, Centrocytic Small Cell, Biological Markers, Viral Marker, beta-cat-arm, Surrogate Endpoints, PCI-32765, CCI 779, determination, Laboratory, RAY, cD1, Biochemical, rapamycin 42-(2, Endpoint, myc-B, histology, DmelCG10798, MYC, Myc, AIP1, Germinoblastoma, Serum, mcIAP1, Tp53, beta-cat, B430311C09Rik, AU040256, Mutations, Relative, Malignant Lymphomas, Laboratory Markers, c-MYC, c-Myc, EG:BACN5I9.1, Biological, ray, bbl, Biological Factor, ARC, 3, myc, Lymphomas, anatomy and histology, Non Polyadenylated, ARM, RNA Gene Products, Arm, beta-Cat, Reticulolymphosarcoma, imprinted and ancient gene protein, treatment, increased, c-myc, HAIP1, LRCC, Gene Expressions, cIAP2, cIAP1, cIAP-2, BCC7, cIAP-1, Small-Cell Lymphomas, dm/dMyc, Intervention Study, CycD1, chromatid, Dm Arm, arm, genetic, Upper, Malignant Lymphoma, Sarcoma, geographical area, Torisel, Immune, Markers, scientific observation, Viral Markers, disease management, CIAP2, Therapies, ccnd1a, CG7776, 9530019H02Rik, single-organism behavior, rapamycin, Therapy, Upper Arms, Viral, Surrogate Endpoint, Process, dmyc1, AU016757, ribose nucleic acid, AW107670, familial, e(Pc), ribonucleic acids, Centrocytic, Biochemical Markers, beta-catenin/Arm, MIAP2, MIAP1, Biologic Marker, L[[3]]CP3, Acceptance Processes, Acceptance Process, KU-MEL-1, AW146227, Reticulolymphosarcomas, Dm, Marker, Ribonukleinsaeure, Relative Risks, NOP, pentosenucleic acids, HLRCC, Ribonucleic acids, bfy, Germinoblastic, response to treatment, mMyc, bcl-1, l(1)G0354, Acid, l(1)G0234, DmelCG7776, Factors, positional polypeptide feature, End Points, Risk, death rate, l(1)G0359, MLYM, Immunologic, IAP2, Germinoblastomas, Laboratory Marker, d-myc, EG:86E4.6, IAP1, Treatments, D-Myc, Myc2, NS21, Niard, lymphoma, Centrocytic Small-Cell Lymphomas, myc2, Patient, Brachiums, Chromosome, Biochemical Marker, betacat, t12687 ALR Dm, DmelLcp3, E(PC), Lymphoma, Raja trachyderma, BG:DS02740.11, anon-48Ac, ALDR1, P53, Centrocytic Small-Cell Lymphoma, p44, bhy, Mantle-Cell Lymphomas, inherited genetic, PCI 32765, DmelCG11579, Poorly Differentiated, Mantle Cell Lymphoma, dMyc1, MRTL, E430016J11Rik, accessory, CG10798, GH05739, dm/myc, Clinical Markers, region or site annotation, Processes, Clinical Marker, l(1)G0139, p53, Gene, Malignant, Germinoblastic Sarcoma, LFS1, Ximpact, supernumerary, dMyc, dMYC, Surrogate End Points, Surrogate Markers, morphology, anon-WO03040301.171, RNF48, RNF49, Client., III, brachium, MYCC, H-ray, GH14582, 1-((3R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo(3, Gene Products, c-myc II, Nop30, bHLHe57, Intermediate Differentiated, Upper Arm, DmelCG2043, Lymphocytic, Sarcomas, Biomarker, study, positional, anatomy, Clinical, lcp3, Biological Marker, LCP-3, Cyl-1, Dmyc, DMYc, Brachium, Small-Cell Lymphoma, 2-bis(hydroxymethyl)propionate), HIAP1, HIAP2, Expressions, Diffuse, Non-Polyadenylated RNA, BHLHE39, Mantle Cell, Immunologic Markers, Trp53, API2, CP3, 4-d)pyrimidin-1-yl)piperidin-1- yl)prop-2-en-1-one, Api2, Nird, RNCMYC, Api1, Poorly-Differentiated, time of survival, Clients, Mantle Zone Lymphoma, prad1, Diffuse Lymphocytic Lymphoma, Expression, TRP53, MCL, MCUL1, Behaviors, constitutitional genetic, bHLHe39, BCL1, Immunologic Marker, l(1)2Bv, ccnd1, dmyc, Biologic, measuring, Imbruvica, RNA, D11S287E, LcpIII, ALR, Mantle-Cell Lymphoma, Birc3, Birc2, Serum Markers, End Point, Intermediate, PCI32765, RNS, Factor, Client, HEL-S-6, impact-a, Immune Marker, Xp53, l(1)arm, PRAD1, prophase chromosome, survival, Arms, c-IAP2, Surrogate End Point, yeast nucleic acid, chemical analysis, U21B31, sequence, DD3, AI327039, imprinted and ancient gene protein homolog, IMPACT, MIHB, Germinoblastic Sarcomas, MIHC, physiological response to stimulus, rare (European definition), LCP3, Mantle-Cell, Relative Risk, Biologic Markers, Biologic Factor, Acceptance, ribonucleic acid, CLECSF8, Serum Marker, CCI-779, RAB1C, DMLCP3, Mantle-Zone, Surrogate, l(2)28-28-12, increased number, MALT2, interphase chromosome, Non Polyadenylated RNA, Biologic Factors, Endpoints, Risks, Centrocytic Small-Cell, Non-Polyadenylated, anon-35Fa, patient, Ribonucleic Acid, l(1)G0192, Surrogate Marker, primary structure of sequence macromolecule, upper extremity, CG11579, DmelCG5861, present in greater numbers in organism, Small-Cell, Lymphocytic Lymphoma, Therapeutic, anon-35Fc, DEL, Mantle-Zone Lymphomas, Indexes, Treatment, assay, CG2043, 42-(3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate), hereditary, RWDD5, lymphoid cancer, Immune MarkersfalseMolecular determinants of outcomes in relapsed mantle cell lymphoma treated with ibrutinib or temsirolimus in the MCL3001 (RAY) trialMantle cell lymphoma (MCL) is a rare, incurable lymphoma subtype characterized by heterogeneous outcomes. In order to better understand the clinical behavior and response to treatment, powerful predictive biomarkers are needed. Using residual archived material from patients enrolled in the MCL3001 (RAY) study, we performed a detailed analysis of gene expression and genetic sequencing. This phase III clinical trial randomized patients with relapsed or refractory MCL to treatment with either ibrutinib or temsirolimus. We confirmed the prognostic capability of the RNA expression proliferation assay MCL35 in this cohort treated with novel agents, which outperformed the simplified MCL International Prognostic Index in discriminating patients with different outcomes. Regardless of treatment arm, we demonstrated that this assay captures the risk conferred by known biological factors, such as increased MYC-expression, blastoid morphology, aberrations of TP53, and truncated CCND1 3’untranslated region. We further showed the negative impact of BIRC3 mutations/deletions on outcomes in this cohort, and identified that deletion of chromosome 8p23.3 also has a deleterious effect on survival. Restricted to patients with deletions/alterations in TP53, ibrutinib appeared to abrogate the deleterious impact on outcome. These data illustrate the potential to perform a molecular analysis of predictive biomarkers from routine patient samples that can meaningfully inform clinical practice.2022-10-10 15:48:51EGAS000010063429606EGAD00001008975EGAC00001002715