TY - JOUR
T1 - Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma
T2 - final results from a phase 2 randomised study (ROMULUS)
AU - Morschhauser, Franck
AU - Flinn, Ian W.
AU - Advani, Ranjana
AU - Sehn, Laurie H.
AU - Diefenbach, Catherine
AU - Kolibaba, Kathryn
AU - Press, Oliver W.
AU - Salles, Gilles
AU - Tilly, Hervé
AU - Chen, Andy I.
AU - Assouline, Sarit
AU - Cheson, Bruce D.
AU - Dreyling, Martin
AU - Hagenbeek, Anton
AU - Zinzani, Pier Luigi
AU - Jones, Surai
AU - Cheng, Ji
AU - Lu, Dan
AU - Penuel, Elicia
AU - Hirata, Jamie
AU - Wenger, Michael
AU - Chu, Yu Waye
AU - Sharman, Jeff
N1 - Funding Information:
This study was supported by F Hoffmann-La Roche, and was designed by the funder (F Hoffmann-La Roche) and authors. Data were collected by the authors and their research teams, and were interpreted by the authors and funder. All authors had full access to the study data. The funder provided medical writing support. The corresponding author had full access to all the study data and final responsibility for the decision to submit for publication.
Funding Information:
FM reports honoraria for advisory board participation and scientific lectures from Bristol-Myers Squibb, Celgene, Gilead, Janssen, and Roche/Genentech; and consultancy fees for Gilead/Servier. IWF reports research funding from Genentech; and grants from Agios, ArQule, Beigene, Calithera, Celgene, Constellation, Curis, F Hoffmann-La Roche, Forma, Forty-Seven, Genentech, Gilead, Incyte, Infinity, Janssen, KITE, Merck, Novartis, Pfizer, Pharmacyclics, Portola, Seattle Genetics, Takeda, TG Therapeutics, Trillium, and Verastem. RA reports personal fees for advisory board participation for Agensys, AstraZeneca, Autolus, Bayer Healthcare Pharmaceuticals, Bristol-Myers Squibb, Celgene, Cell Medica, Forty-Seven, Gilead, Infinity, Janssen, Juno, Kura, Merck, Millennium, NanoString, Pharmacyclics, Regeneron, Roche/Genentech, Seattle Genetics, Spectrum Pharmaceuticals, Sutro, and Teva. LHS reports consultancy fees or has received honoraria from F Hoffman La-Roche/Genentech, AbbVie, Amgen, Apobiologix, AstraZeneca, Acerta, Celgene, Janssen, Lundbeck, Karyopharm, Morphosys, Merck, Seattle Genetics, Teva, Takeda, and has received research funding from F Hoffman La-Roche/Genentech. CD reports consultancy fees and research funding from Genentech. KK reports consultancy fees for Gilead, research funding from Acerta, Celgene, Cell Therapeutics, Genentech, Gilead, Janssen, Novartis, Pharmcyclics, Seattle Genetics, and TG Therapeutics; and honoraria from TG Therapeutics. OWP reported research funding from Roche, honoraria from Bristol-Myers Squibb and Roche, and consultancy fees from Bayer. GS reports personal fees for consultancy, advisory board participation, or speaking at symposia from Amgen, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Kite, Merck, Morphosys, Novartis, Roche, and Servier; and research funding from Roche. HT reports grants and personal fees from Celgene; personal fees and non-financial support from Roche; and personal fees from Karyopharm and AstraZeneca. AIC reports consultancy fees from Genentech/Roche, Kite, and Bayer. SA reports personal fees for speakers' bureau, advisory board participation, and research funding from Janssen and Pfizer; fees for travel support and research funding from Roche; and fees for speakers' bureau and research funding from Bristol-Myers Squibb. BDC reports consultancy to Roche/Genentech and research funding to the institution from Roche/Genentech. MD reports research funding, personal fees for advisory board participation, speakers' honoraria, institutional support of academic trials, and travel support from Roche. AH reports personal fees for advisory work from Takeda Oncology, USA. PLZ reports personal fees for advisory board participation from AbbVie, Celgene, Janssen, Morphosys, Roche, and Takeda. SJ reports employment and consultancy for Genentech. JC is an employee of F Hoffmann-La Roche. DL, EP, JH, MW, and Y-WC are employees of Genentech. JS reports research funding from Acerta, Celgene, Genentech, Gilead, Seattle Genetics, and TG Therapeutics; and consultancy fees from Acerta, Celgene, Genentech, Gilead, Seattle Genetics, and TG Therapeutics.
Funding Information:
We thank the patients and their families, study investigators, study coordinators, and support staff. Medical writing support for this Article was provided by Joanne Vaughan of Envision Pharma Group, and funded by F Hoffmann-La Roche. Medical editorial support was provided by Rachel Hubbard of Gardiner-Caldwell Communications, and was funded by F Hoffmann-La Roche.
PY - 2019/5
Y1 - 2019/5
N2 - Background: Antibody–drug conjugates (ADCs)polatuzumab vedotin (pola)and pinatuzumab vedotin (pina)showed clinical activity and tolerability in phase 1 trials. The aim of this multicentre, open-label, phase 2 study was to compare rituximab plus pola (R-pola)or pina (R-pina)in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Methods: In this phase 2 randomised study at 39 investigational sites in six countries, patients were randomly assigned (1:1), by use of a dynamic hierarchical randomisation scheme, to receive R-pola or R-pina (375 mg/m2 rituximab plus 2·4 mg/kg ADCs)every 21 days until disease progression or unacceptable toxicity up to 1 year. Treatment allocations were not masked to the investigator, patients or sponsor after the patients were enrolled and randomly assigned. The primary objectives were safety and tolerability, and antitumour response. The study is registered with ClinicalTrials.gov, number NCT01691898, and is closed to accrual. Findings: 81 patients with diffuse large B-cell lymphoma and 42 with follicular lymphoma were recruited between Sept 27, 2012, and Oct 10, 2013, and were assigned to treatment. 81 patients with diffuse large B-cell lymphoma and 41 patients with follicular lymphoma were eligible for analysis. Of the 42 patients with diffuse large B-cell lymphoma who received R-pina, 25 (60%, 95% CI 43–74)achieved an objective response and 11 (26%, 95% CI 14–42)achieved a complete response. Of the 39 patients in this cohort who received R-pola, 21 (54%, 95% CI 37–70)achieved an objective response, and eight (21%, 95% CI 9–36)achieved a complete response. Of the 21 patients in the follicular lymphoma cohort who received R-pina, 13 (62%, 95% CI 38–82)achieved an objective response, and one (5%, 95% CI 0·1–24)achieved a complete response. Of the 20 patients in this cohort who received R-pola, 14 (70%, 95% CI 46–88)achieved an objective response, and nine (45%, 95% CI 23–68)achieved a complete response. In the diffuse large B-cell lymphoma cohort, grade 3–5 adverse events occurred in 33 (79%)of 42 patients receiving R-pina (most common were neutropenia [29%]and hyperglycaemia [10%]; nine [21%]grade 5 adverse events, five of which were infection-related), and in 30 (77%)of 39 patients receiving R-pola (most common were neutropenia [23%], anaemia [8%]and diarrhoea [8%]; no grade 5 adverse events). In the follicular lymphoma cohort, grade 3–5 adverse events occurred in 13 (62%)of 21 patients receiving R-pina (most common were neutropenia [29%]and hyperglycaemia [14%]; no grade 5 adverse events)and in ten (50%)of 20 patients receiving R-pola (most common were neutropenia [15%]and diarrhoea [10%]; one grade 5 adverse event). Interpretation: R-pina and R-pola are potential treatment options in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Pola was selected by the study funder for further development in non-Hodgkin lymphoma, partly because of longer durations of response than pina, and an overall benefit–risk favouring R-pola. Funding: F Hoffmann-La Roche.
AB - Background: Antibody–drug conjugates (ADCs)polatuzumab vedotin (pola)and pinatuzumab vedotin (pina)showed clinical activity and tolerability in phase 1 trials. The aim of this multicentre, open-label, phase 2 study was to compare rituximab plus pola (R-pola)or pina (R-pina)in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Methods: In this phase 2 randomised study at 39 investigational sites in six countries, patients were randomly assigned (1:1), by use of a dynamic hierarchical randomisation scheme, to receive R-pola or R-pina (375 mg/m2 rituximab plus 2·4 mg/kg ADCs)every 21 days until disease progression or unacceptable toxicity up to 1 year. Treatment allocations were not masked to the investigator, patients or sponsor after the patients were enrolled and randomly assigned. The primary objectives were safety and tolerability, and antitumour response. The study is registered with ClinicalTrials.gov, number NCT01691898, and is closed to accrual. Findings: 81 patients with diffuse large B-cell lymphoma and 42 with follicular lymphoma were recruited between Sept 27, 2012, and Oct 10, 2013, and were assigned to treatment. 81 patients with diffuse large B-cell lymphoma and 41 patients with follicular lymphoma were eligible for analysis. Of the 42 patients with diffuse large B-cell lymphoma who received R-pina, 25 (60%, 95% CI 43–74)achieved an objective response and 11 (26%, 95% CI 14–42)achieved a complete response. Of the 39 patients in this cohort who received R-pola, 21 (54%, 95% CI 37–70)achieved an objective response, and eight (21%, 95% CI 9–36)achieved a complete response. Of the 21 patients in the follicular lymphoma cohort who received R-pina, 13 (62%, 95% CI 38–82)achieved an objective response, and one (5%, 95% CI 0·1–24)achieved a complete response. Of the 20 patients in this cohort who received R-pola, 14 (70%, 95% CI 46–88)achieved an objective response, and nine (45%, 95% CI 23–68)achieved a complete response. In the diffuse large B-cell lymphoma cohort, grade 3–5 adverse events occurred in 33 (79%)of 42 patients receiving R-pina (most common were neutropenia [29%]and hyperglycaemia [10%]; nine [21%]grade 5 adverse events, five of which were infection-related), and in 30 (77%)of 39 patients receiving R-pola (most common were neutropenia [23%], anaemia [8%]and diarrhoea [8%]; no grade 5 adverse events). In the follicular lymphoma cohort, grade 3–5 adverse events occurred in 13 (62%)of 21 patients receiving R-pina (most common were neutropenia [29%]and hyperglycaemia [14%]; no grade 5 adverse events)and in ten (50%)of 20 patients receiving R-pola (most common were neutropenia [15%]and diarrhoea [10%]; one grade 5 adverse event). Interpretation: R-pina and R-pola are potential treatment options in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Pola was selected by the study funder for further development in non-Hodgkin lymphoma, partly because of longer durations of response than pina, and an overall benefit–risk favouring R-pola. Funding: F Hoffmann-La Roche.
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U2 - 10.1016/S2352-3026(19)30026-2
DO - 10.1016/S2352-3026(19)30026-2
M3 - Article
C2 - 30935953
AN - SCOPUS:85064588955
VL - 6
SP - e254-e265
JO - The Lancet Haematology
JF - The Lancet Haematology
SN - 2352-3026
IS - 5
ER -