Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu klinické zkoušky, fáze III, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem
Grantová podpora
P30 CA008748
NCI NIH HHS - United States
PubMed
34904799
PubMed Central
PMC11702892
DOI
10.1056/nejmoa2115304
Knihovny.cz E-zdroje
- MeSH
- cyklofosfamid škodlivé účinky terapeutické užití MeSH
- difúzní velkobuněčný B-lymfom farmakoterapie mortalita MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- doxorubicin škodlivé účinky terapeutické užití MeSH
- dvojitá slepá metoda MeSH
- imunokonjugáty aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- monoklonální protilátky aplikace a dávkování škodlivé účinky MeSH
- prednison škodlivé účinky terapeutické užití MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
- rituximab škodlivé účinky terapeutické užití MeSH
- senioři MeSH
- vinkristin škodlivé účinky terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- cyklofosfamid MeSH
- doxorubicin MeSH
- imunokonjugáty MeSH
- monoklonální protilátky MeSH
- polatuzumab vedotin MeSH Prohlížeč
- prednison MeSH
- R-CHOP protocol MeSH Prohlížeč
- rituximab MeSH
- vinkristin MeSH
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells. METHODS: We conducted a double-blind, placebo-controlled, international phase 3 trial to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival and safety. RESULTS: Overall, 879 patients underwent randomization: 440 were assigned to the pola-R-CHP group and 439 to the R-CHOP group. After a median follow-up of 28.2 months, the percentage of patients surviving without progression was significantly higher in the pola-R-CHP group than in the R-CHOP group (76.7% [95% confidence interval (CI), 72.7 to 80.8] vs. 70.2% [95% CI, 65.8 to 74.6] at 2 years; stratified hazard ratio for progression, relapse, or death, 0.73 by Cox regression; 95% CI, 0.57 to 0.95; P = 0.02). Overall survival at 2 years did not differ significantly between the groups (88.7% [95% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6% [95% CI, 85.6 to 91.6] in the R-CHOP group; hazard ratio for death, 0.94; 95% CI, 0.65 to 1.37; P = 0.75). The safety profile was similar in the two groups. CONCLUSIONS: Among patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP. (Funded by F. Hoffmann-La Roche/Genentech; POLARIX ClinicalTrials.gov number, NCT03274492.).
Zobrazit více v PubMed
Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin 2016;66:443–59. PubMed
Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002;346:235–42. PubMed
Pfreundschuh M, Kuhnt E, Trümper L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. The Lancet Oncology 2011;12:1013–22. PubMed
Sehn LH, Salles G. Diffuse large B-cell lymphoma. N Engl J Med 2021;384:842–58. PubMed PMC
Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood 2017;130:1800–8. PubMed PMC
Cunningham D, Hawkes EA, Jack A, et al. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet 2013;381:1817–26. PubMed
Delarue R, Tilly H, Mounier N, et al. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03–6B study): a randomised phase 3 trial. The Lancet Oncology 2013;14:525–33. PubMed
Bartlett NL, Wilson WH, Jung SH, et al. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol 2019;37:1790–9. PubMed PMC
Lugtenburg PJ, de Nully Brown P, van der Holt B, et al. Rituximab-CHOP with early rituximab intensification for diffuse large B-cell lymphoma: a randomized phase III trial of the HOVON and the Nordic Lymphoma Group (HOVON-84). J Clin Oncol 2020;38:3377–87. PubMed
Jaeger U, Trneny M, Melzer H, et al. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica 2015;100:955–63. PubMed PMC
Thieblemont C, Tilly H, Gomes da Silva M, et al. Lenalidomide Maintenance Compared With Placebo in Responding Elderly Patients With Diffuse Large B-Cell Lymphoma Treated With First-Line Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone. J Clin Oncol 2017;35:2473–81. PubMed
Vitolo U, Trneny M, Belada D, et al. Obinutuzumab or Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Previously Untreated Diffuse Large B-Cell Lymphoma. J Clin Oncol 2017;35:3529–37. PubMed
Nowakowski GS, Chiappella A, Gascoyne RD, et al. ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma. J Clin Oncol 2021;39:1317–28. PubMed PMC
Younes A, Sehn LH, Johnson P, et al. Randomized phase III Trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol 2019;37:1285–95. PubMed PMC
Goy A. Succeeding in breaking the R-CHOP ceiling in DLBCL: learning from negative trials. J Clin Oncol 2017;35:3519–22. PubMed
Dornan D, Bennett F, Chen Y, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood 2009;114:2721–9. PubMed
Pfeifer M, Zheng B, Erdmann T, et al. Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes. Leukemia 2015;29:1578–86. PubMed
Okazaki M, Luo Y, Han T, Yoshida M, Seon BK. Three new monoclonal antibodies that define a unique antigen associated with prolymphocytic leukemia/non-Hodgkin's lymphoma and are effectively internalized after binding to the cell surface antigen. Blood 1993;81:84–94. PubMed
Polson AG, Yu SF, Elkins K, et al. Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. Blood 2007;110:616–23. PubMed
Palanca-Wessels MC, Czuczman M, Salles G, et al. Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. The Lancet Oncology 2015;16:704–15. PubMed
Morschhauser F, Flinn IW, Advani R, et al. Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol 2019;6:e254–e65. PubMed
Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 2020;38:155–65. PubMed PMC
Tilly H, Morschhauser F, Bartlett NL, et al. Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. The Lancet Oncology 2019;20:998–1010. PubMed
World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Jama 2013;310:2191–4. PubMed
Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375–90. PubMed PMC
International Non-Hodgkin's Lymphoma Prognostic Factors P. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med 1993;329:987–94. PubMed
Bretz F, Maurer W, Brannath W, Posch M. A graphical approach to sequentially rejective multiple test procedures. Statistics in Medicine 2009;28:586–604. PubMed
Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014;32:3059–68. PubMed PMC
Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 1994;81:515–26.
Chapuy B, Stewart C, Dunford AJ, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nature Med 2018;24:679–90. PubMed PMC
Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000;403:503–11. PubMed
Schmitz R, Wright GW, Huang DW, et al. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma. New England Journal of Medicine 2018;378:1396–407. PubMed PMC
Ennishi D, Jiang A, Boyle M, et al. Double-Hit Gene Expression Signature Defines a Distinct Subgroup of Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma. Journal of Clinical Oncology 2018;37:190–201. PubMed PMC
Maurer MJ, Ghesquières H, Jais JP, et al. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol 2014;32:1066–73. PubMed PMC
Maurer MJ, Habermann TM, Shi Q, et al. Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) enrolled on randomized clinical trials. Ann Oncol 2018;29:1822–7. PubMed PMC
Shi Q, Schmitz N, Ou FS, et al. Progression-Free Survival as a Surrogate End Point for Overall Survival in First-Line Diffuse Large B-Cell Lymphoma: An Individual Patient-Level Analysis of Multiple Randomized Trials (SEAL). J Clin Oncol 2018;36:2593–602. PubMed PMC
Horwitz S, O'Connor OA, Pro B, et al. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet 2019;393:229–40. PubMed PMC
Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options
Targeted Drug Delivery and Theranostic Strategies in Malignant Lymphomas
ClinicalTrials.gov
NCT03274492