{"entity":{"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","aka":[],"tldr":"Replacing one chemotherapy drug in R-CHOP with a CD79b antibody-drug conjugate modestly reduced progression (2-year PFS 76.7% versus 70.2%) without changing survival or side effects.","summary":"POLARIX randomised 879 previously untreated patients with diffuse large B-cell lymphoma (IPI 2-5, age 18-80) to pola-R-CHP (polatuzumab vedotin replacing vincristine) or standard R-CHOP for six cycles plus two rituximab doses. The primary endpoint was investigator-assessed PFS. At two years PFS was 76.7% versus 70.2% (hazard ratio 0.73) while overall survival was identical (88.7% versus 88.6%) and the safety profiles were similar. Exploratory subgroups suggested most benefit in activated B-cell-like subtype, older patients and higher IPI, with little or no benefit in germinal-centre subtype. It was the first regimen to beat R-CHOP in two decades of trials.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2115304"},{"label":"ClinicalTrials.gov NCT03274492","url":"https://clinicaltrials.gov/study/NCT03274492"}],"tags":[],"related":["lymphoma-roadmap","paper-polargo-polatuzumab-r-gemox-dlbcl-jco-2026","polar-bear"],"cancers":["dlbcl"],"sections":[],"technologies":["adc"],"targets":["cd79b","cd20"],"drugs":["polatuzumab-vedotin","rituximab","doxorubicin","vincristine"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["pfs","os"],"trials":["polarix"],"people":[],"bottlenecks":["b-drug-pricing","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2115304","authors":"Tilly H, Morschhauser F, Sehn LH, et al.","paperType":"rct","findings":["879 untreated DLBCL patients, IPI 2-5; pola-R-CHP vs R-CHOP.","2-year PFS 76.7% vs 70.2%; hazard ratio 0.73 (about 6.5 percentage points absolute).","2-year overall survival 88.7% vs 88.6%; no difference.","Grade 3-4 adverse events 57.7% vs 57.5%; peripheral neuropathy rates similar.","Exploratory: benefit concentrated in ABC subtype, IPI 3-5 and age over 60; GCB subtype showed none."],"whatItMeans":"POLARIX gave the first new first-line standard for DLBCL since rituximab was added to CHOP, and pola-R-CHP is now approved and widely used, especially in higher-risk or ABC-type disease. The gain is modest and survival is unchanged, so many clinicians still use R-CHOP in lower-risk or GCB-type patients. Cost and subgroup uncertainty drive ongoing debate.","caveats":["No overall survival benefit; the PFS gain is modest in absolute terms.","Subgroup effects are exploratory and hypothesis-generating, yet influence practice.","Excluded very low IPI (0-1) and age over 80.","High cost relative to a generic-based regimen."],"changedPractice":true,"participants":879},"route":"/key-papers/paper-polarix-polatuzumab-rchp-nejm-2022/","neighbours":{"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/"}],"paper":[{"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/"}],"trial":[{"id":"polar-bear","kind":"trial","name":"POLAR BEAR","route":"/trials/polar-bear/"},{"id":"polarix","kind":"trial","name":"POLARIX","route":"/trials/polarix/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"},{"id":"cd79b","kind":"target","name":"CD79b","route":"/targets/cd79b/"}],"drug":[{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"polatuzumab-vedotin","kind":"drug","name":"Polatuzumab vedotin","route":"/drugs/polatuzumab-vedotin/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"person":[{"id":"gilles-salles","kind":"person","name":"Gilles Salles","route":"/people/gilles-salles/"},{"id":"herve-tilly","kind":"person","name":"Hervé Tilly","route":"/people/herve-tilly/"}]}}