{"entity":{"id":"polatuzumab-vedotin","kind":"drug","name":"Polatuzumab vedotin","aka":[],"tldr":"Polatuzumab vedotin is an ADC against CD79b that, swapped into the classic R-CHOP regimen, became the first improvement on frontline lymphoma therapy in twenty years.","summary":"POLARIX (2022): Pola-R-CHP versus R-CHOP in untreated DLBCL, IPI 2-5. Two-year PFS 76.7% vs 70.2% (HR 0.73); five-year PFS 64.9% vs 59.1% (HR 0.77) with OS HR 0.85, not significant. Approved US April 2023 for frontline DLBCL (IPI ≥2) and since 2019 with bendamustine-rituximab for relapsed disease. Peripheral neuropathy is the class toxicity.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Polatuzumab_vedotin","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Polatuzumab%20vedotin"},{"label":"Davis et al., Nature 2010: chronic active B-cell receptor signalling in diffuse large B-cell lymphoma","url":"https://doi.org/10.1038/nature08638"}],"tags":[],"related":[],"cancers":["dlbcl"],"sections":[],"technologies":["adc"],"targets":["cd79b"],"drugs":[],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["payload","bystander-effect"],"trials":["polarix","nct04844866","nct03671018","nct03533283","nct06890884"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lymphoma biology: CD79b is chosen not because it is more specific than CD20 but because it internalises. It is part of the B-cell receptor complex, which is continuously taken into the cell, so it can carry monomethyl auristatin E inside; CD20 cannot. Expression is above 95% in diffuse large B-cell lymphoma, so nothing is tested before the first dose, and the dose-limiting toxicity is the payload, as cumulative peripheral neuropathy, rather than the antigen (Davis 2010)."],"brand":"Polivy","modality":"ADC","payload":"MMAE (tubulin inhibitor), DAR ~3.5","linker":"mc-vc-PABC, protease-cleavable","mechanism":"Humanised anti-CD79b IgG1 internalised via the B-cell receptor complex; MMAE released by cathepsin B; bystander killing.","approvals":[{"region":"US","year":2019,"indication":"Relapsed/refractory DLBCL with bendamustine-rituximab after ≥2 lines (accelerated)"},{"region":"US","year":2023,"indication":"Untreated DLBCL, IPI ≥2, with R-CHP (Pola-R-CHP)"}],"mechanismSteps":["Antibody binds CD79b on the B-cell receptor complex","Complex internalised and trafficked to lysosome","Cathepsin cleaves the vc linker, freeing MMAE","MMAE disrupts microtubules; mitotic arrest and apoptosis","Permeable MMAE diffuses to neighbouring cells"],"dosing":{"route":"IV","schedule":"1.8 mg/kg every 21 days for 6 cycles with R-CHP (frontline) or with BR (relapsed)","modifications":"Reduce to 1.4 mg/kg for grade 2-3 neuropathy; discontinue for grade 4","monitoring":"Neuropathy, neutropenia, infections, infusion reactions","source":"https://www.gene.com/download/pdf/polivy_prescribing.pdf"},"toxicity":[{"event":"Peripheral neuropathy","anyGradePct":52.9,"grade3PlusPct":1.6,"note":"POLARIX Pola-R-CHP arm"},{"event":"Neutropenia","grade3PlusPct":28.3},{"event":"Febrile neutropenia","grade3PlusPct":13.8},{"event":"Diarrhoea","anyGradePct":30.8}],"access":[],"regulatoryEvents":[{"date":"2019-06-10","type":"accelerated-approval","region":"US","note":"Accelerated approval with BR in R/R DLBCL","indication":"In combination with bendamustine and a rituximab product for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, after at least two prior therapies."},{"date":"2023-04-19","type":"conversion","region":"US","note":"Frontline Pola-R-CHP (POLARIX)","indication":"In combination with bendamustine and a rituximab product for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, after at least two prior therapies."}]},"route":"/drugs/polatuzumab-vedotin/","neighbours":{"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"cd79b","kind":"target","name":"CD79b","route":"/targets/cd79b/"}],"company":[{"id":"chugai","kind":"company","name":"Chugai Pharmaceutical","route":"/companies/chugai/"},{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"lymphoma-tx-uk-versus-us","kind":"term","name":"British and American lymphoma practice: where they differ, and why","route":"/terms/lymphoma-tx-uk-versus-us/"},{"id":"bystander-effect","kind":"term","name":"Bystander effect (ADC)","route":"/terms/bystander-effect/"},{"id":"payload","kind":"term","name":"Payload (ADC)","route":"/terms/payload/"},{"id":"lymphoma-tx-regimen-alphabet","kind":"term","name":"The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest","route":"/terms/lymphoma-tx-regimen-alphabet/"},{"id":"lymphoma-tx-uk-access","kind":"term","name":"What the NHS in England funds for lymphoma, appraisal by appraisal","route":"/terms/lymphoma-tx-uk-access/"}],"trial":[{"id":"nct06890884","kind":"trial","name":"A Clinical Study of Zilovertamab Vedotin (MK-2140) Plus Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Polatuzumab Vedotin Plus R-CHP in People With Diffuse Large B-cell Lymphoma (DLBCL) (MK-2140-011/waveLINE-011)","route":"/trials/nct06890884/"},{"id":"nct03671018","kind":"trial","name":"A Study to Evaluate the Safety and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in B-Cell Non-Hodgkin Lymphoma","route":"/trials/nct03671018/"},{"id":"nct03533283","kind":"trial","name":"An Open-Label Phase lB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma","route":"/trials/nct03533283/"},{"id":"nct04844866","kind":"trial","name":"Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients","route":"/trials/nct04844866/"},{"id":"polar-bear","kind":"trial","name":"POLAR BEAR","route":"/trials/polar-bear/"},{"id":"polargo","kind":"trial","name":"POLARGO","route":"/trials/polargo/"},{"id":"polarix","kind":"trial","name":"POLARIX","route":"/trials/polarix/"},{"id":"sunmo","kind":"trial","name":"SUNMO","route":"/trials/sunmo/"}],"drug":[{"id":"mosunetuzumab","kind":"drug","name":"Mosunetuzumab","route":"/drugs/mosunetuzumab/"}],"pairing":[{"id":"bispecific-plus-adc-lymphoma","kind":"pairing","name":"CD20 bispecific + CD79b ADC (mosunetuzumab + polatuzumab)","route":"/pairings/bispecific-plus-adc-lymphoma/"}],"idea":[{"id":"idea-ctdna-guided-dlbcl-frontline","kind":"idea","name":"ctDNA-guided escalation and de-escalation in frontline DLBCL","route":"/ideas/idea-ctdna-guided-dlbcl-frontline/"}],"biomarker":[{"id":"cd79b-itam-mutation","kind":"biomarker","name":"CD79B ITAM mutation","route":"/biomarkers/cd79b-itam-mutation/"}],"paper":[{"id":"paper-polarix-polatuzumab-rchp-nejm-2022","kind":"paper","name":"POLARIX: swapping vincristine for the antibody-drug conjugate polatuzumab vedotin in first-line treatment of diffuse large B-cell lymphoma","route":"/key-papers/paper-polarix-polatuzumab-rchp-nejm-2022/"},{"id":"paper-polargo-polatuzumab-r-gemox-dlbcl-jco-2026","kind":"paper","name":"Polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin in relapsed or refractory diffuse large B-cell lymphoma: results from the phase III, randomized POLARGO trial","route":"/key-papers/paper-polargo-polatuzumab-r-gemox-dlbcl-jco-2026/"}],"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}]}}