dc.date.accessioned | 2023-02-01T17:42:04Z | |
dc.date.available | 2023-02-01T17:42:04Z | |
dc.date.created | 2022-12-25T11:15:16Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Schjesvold, Fredrik Hellem Paiva, Bruno Ribrag, Vincent Rodriguez-Otero, Paula San-Miguel, Jesus F. Robak, Pawel Hansson, Markus Onishi, Maika Hamidi, Habib Malhi, Vikram Dail, Monique Javery, Apurva Ku, Grace Raab, Marc S. . Cobimetinib alone and plus venetoclax with/without atezolizumab in patients with relapsed/refractory multiple myeloma. Clinical Lymphoma, Myeloma & Leukemia. 2022, 23(1), e59-e70 | |
dc.identifier.uri | http://hdl.handle.net/10852/99552 | |
dc.description.abstract | 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; combination 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 venetoclax (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 demonstrated 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 biomarker-driven approach for ven in MM. | |
dc.language | EN | |
dc.publisher | CIG Media Group, LP | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | Cobimetinib alone and plus venetoclax with/without atezolizumab in patients with relapsed/refractory multiple myeloma | |
dc.title.alternative | ENEngelskEnglishCobimetinib alone and plus venetoclax with/without atezolizumab in patients with relapsed/refractory multiple myeloma | |
dc.type | Journal article | |
dc.creator.author | Schjesvold, Fredrik Hellem | |
dc.creator.author | Paiva, Bruno | |
dc.creator.author | Ribrag, Vincent | |
dc.creator.author | Rodriguez-Otero, Paula | |
dc.creator.author | San-Miguel, Jesus F. | |
dc.creator.author | Robak, Pawel | |
dc.creator.author | Hansson, Markus | |
dc.creator.author | Onishi, Maika | |
dc.creator.author | Hamidi, Habib | |
dc.creator.author | Malhi, Vikram | |
dc.creator.author | Dail, Monique | |
dc.creator.author | Javery, Apurva | |
dc.creator.author | Ku, Grace | |
dc.creator.author | Raab, Marc S. | |
cristin.unitcode | 185,53,18,75 | |
cristin.unitname | K.G. Jebsen senter for B-cellekreft - del UiO | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 2097355 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Clinical Lymphoma, Myeloma & Leukemia&rft.volume=23&rft.spage=e59&rft.date=2022 | |
dc.identifier.jtitle | Clinical Lymphoma, Myeloma & Leukemia | |
dc.identifier.volume | 23 | |
dc.identifier.issue | 1 | |
dc.identifier.startpage | e59 | |
dc.identifier.endpage | e70 | |
dc.identifier.doi | https://doi.org/10.1016/j.clml.2022.10.006 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2152-2650 | |
dc.type.version | PublishedVersion | |