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dc.creatorSchjesvold, F.H. (Fredrik H.)-
dc.creatorLourenco-Paiva, B.D. (Bruno David)-
dc.creatorRibrag, V. (Vincent)-
dc.creatorRodriguez-Otero, P. (Paula)-
dc.creatorSan-Miguel-Izquierdo, J. (Jesús Fernando)-
dc.creatorRobak, P. (Pawel)-
dc.creatorHansson, M. (Markus)-
dc.creatorOnishi, M. (Maika)-
dc.creatorHamidi, H. (Habib)-
dc.creatorMalhi, V. (Vikram)-
dc.creatorDail, M. (Monique)-
dc.creatorJavery, A. (Apurva)-
dc.creatorKu, G. (Grace)-
dc.creatorRaab, M.S. (Marc S.)-
dc.date.accessioned2023-04-19T10:32:06Z-
dc.date.available2023-04-19T10:32:06Z-
dc.date.issued2023-
dc.identifier.citationSchjesvold, F.; Lourenco-Paiva, B. (Bruno David); Ribrag, V.; et al. "Cobimetinib alone and plus venetoclax with/without atezolizumab in patients with relapsed/refractory multiple myeloma". Clinical Lymphoma Myeloma and Leukemia. 23 (1), 2023, e59 - e70es
dc.identifier.issn2152-2650-
dc.identifier.urihttps://hdl.handle.net/10171/66017-
dc.description.abstractThis phase IB/II trial evaluated safety and efficacy of cobimetinib alone and in novel combinations with veneto-clax with/without atezolizumab in patients with relapsed/refractory multiple myeloma. Forty-nine patients were enrolled. Cobimetinib alone and in combination with venetoclax with/without atezolizumab was determined to be safe and tolerable; anti-tumor activity was moderate overall but higher in patients with translocation t(11;14). Introduction: Mitogen-activated protein kinase pathway mutations are present in > 50% of patients with relapsed/refractory (R/R) multiple myeloma (MM). MEK inhibitors show limited single-agent activity in R/R MM; combi-nation with B-cell lymphoma-2 (BCL-2) and programmed death-ligand 1 inhibition may improve efficacy. This phase Ib/II trial (NCT03312530) evaluated safety and efficacy of cobimetinib (cobi) alone and in combination with veneto-clax (ven) with/without atezolizumab (atezo) in patients with R/R MM. Patients and Methods: Forty-nine patients were randomized 1:2:2 to cobi 60 mg/day on days 1-21 (n = 6), cobi 40 mg/day on days 1-21 + ven 800 mg/day on days 1-28 with/without atezo 840 mg on days 1 and 15 of 28-day cycles (cobi-ven, n = 22; cobi-ven-atezo, n = 21). Safety run-in cohorts evaluated cobi-ven and cobi-ven-atezo dose levels. Results: Any-grade common adverse events (AEs) with cobi, cobi-ven, and cobi-ven-atezo, respectively, included diarrhea (33.3%, 81.8%, 90.5%) and nausea (16.7%, 50.0%, 66.7%); common grade >= 3 AEs included anemia (0%, 22.7%, 23.8%), neutropenia (0%, 13.6%, 38.1%), and thrombocytopenia (0%, 18.2%, 23.8%). The overall response rate for all-comers was 0% (cobi), 27.3% (cobi-ven), and 28.6% (cobi-ven-atezo), and 0%, 50.0%, and 100%, respectively, in patients with t(11;14) + . Biomarker analysis demon-strated non-t(11;14) patient selection with NRAS /KRAS /BRAF mutation or high BCL-2/BCL-2-L1 ratio ( > 52% of the study population) could enrich for responders to the cobi-ven combination. Conclusions: Cobi-ven and cobi-ven-atezo demonstrated manageable safety with moderate activity in all-comers, and higher activity in patients with t(11;14) + MM, supporting a biomar ker-dr iven approach for ven in MM.-
dc.language.isoen-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.subjectÁrea de Medicina Clínica y Epidemiología-
dc.subjectMitogen-activated protein kinase pathway-
dc.subjectImmunotherapy-
dc.subjectB-cell lymphoma-2-
dc.subjectProgrammed death-ligand 1-
dc.subjectBiomarker-
dc.titleCobimetinib Alone and Plus Venetoclax With/Without Atezolizumab in Patients With Relapsed/Refractory Multiple Myeloma-
dc.typeinfo:eu-repo/semantics/article-
dc.relation.publisherversionhttps://pubmed.ncbi.nlm.nih.gov/36450626/-
dc.description.noteThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)-
dc.identifier.doi10.1016/j.clml.2022.10.006-
dadun.citation.endingPagee70-
dadun.citation.number1-
dadun.citation.publicationNameCLINICAL LYMPHOMA MYELOMA AND LEUKEMIA-
dadun.citation.startingPagee59-
dadun.citation.volume23-
dc.identifier.pmid36450626-

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