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)

被引:205
作者
Morschhauser, Franck [1 ]
Flinn, Ian W. [2 ,3 ]
Advani, Ranjana [4 ]
Sehn, Laurie H. [5 ]
Diefenbach, Catherine [6 ]
Kolibaba, Kathryn [7 ]
Press, Oliver W. [8 ]
Salles, Gilles [9 ]
Tilly, Herve [10 ]
Chen, Andy I. [11 ]
Assouline, Sarit [12 ]
Cheson, Bruce D. [13 ]
Dreyling, Martin [14 ]
Hagenbeek, Anton [15 ]
Zinzani, Pier Luigi [16 ]
Jones, Surai [17 ]
Cheng, Ji [17 ]
Lu, Dan [17 ]
Penuel, Elicia [17 ]
Hirata, Jamie [17 ]
Wenger, Michael [17 ]
Chu, Yu-Waye [17 ]
Sharman, Jeff [18 ,19 ]
机构
[1] Univ Lille, Ctr Hosp Reg Univ Lille, EA 7365, Grp Rech Formes Injectables & Technol Associees, F-59000 Lille, France
[2] Sarah Cannon Res Inst, Nashville, TN USA
[3] Tennessee Oncol, Nashville, TN USA
[4] Stanford Canc Ctr, Stanford, CA USA
[5] BC Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC, Canada
[6] NYU, Med Ctr, New York, NY 10016 USA
[7] US Oncol & Compass Oncol, Vancouver, WA USA
[8] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA
[9] Hosp Civils Lyon, Pierre Benite, France
[10] Ctr Henri Becquerel, Rouen, France
[11] Oregon Hlth & Sci Univ, Portland, OR 97201 USA
[12] Jewish Gen Hosp, Montreal, PQ, Canada
[13] Georgetown Univ Hosp, Washington, DC 20007 USA
[14] Ludwig Maximilian Univ Munich, Univ Hosp, Dept Med 3, Munich, Germany
[15] Acad Med Ctr, Amsterdam, Netherlands
[16] Univ Bologna, Inst Hematol, Bologna, Italy
[17] Genentech Inc, 460 Point San Bruno Blvd, San Francisco, CA 94080 USA
[18] US Oncol, Springfield, OR USA
[19] Willamette Valley Canc Inst, Springfield, OR USA
关键词
ANTIBODY-DRUG CONJUGATE; MULTICENTER; INHIBITION; ANTI-CD22; SAFETY;
D O I
10.1016/S2352-3026(19)30026-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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/m(2) 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 infectionrelated), 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 nonHodgkin lymphoma, partly because of longer durations of response than pina, and an overall benefit-risk favouring R-pola.
引用
收藏
页码:E254 / E265
页数:12
相关论文
共 25 条
[1]   Phase I Study of the Anti-CD22 Antibody-Drug Conjugate Pinatuzumab Vedotin with/without Rituximab in Patients with Relapsed/Refractory B-cell Non-Hodgkin Lymphoma [J].
Advani, Ranjana H. ;
Lebovic, Daniel ;
Chen, Andy ;
Brunvand, Mark ;
Goy, Andre ;
Chang, Julie E. ;
Hochberg, Ephraim ;
Yalamanchili, Sreeni ;
Kahn, Robert ;
Lu, Dan ;
Agarwal, Priya ;
Dere, Randall C. ;
Hsieh, Hsin-Ju ;
Jones, Surai ;
Chu, Yu-Waye ;
Cheson, Bruce D. .
CLINICAL CANCER RESEARCH, 2017, 23 (05) :1167-1176
[2]   A Multicenter Phase II Study of Twice-Weekly Bortezomib plus Rituximab in Patients with Relapsed Follicular Lymphoma: Long-Term Follow-Up [J].
Bari, Alessia ;
Marcheselli, Raffaella ;
Marcheselli, Luigi ;
Alvarez, Isabel ;
Pozzi, Samantha ;
Ferri, Paola ;
Lazzaro, Antonio ;
Fragasso, Alberto ;
Neri, Santo ;
Baldini, Luca ;
Carella, Angelo Michele ;
Angrilli, Francesco ;
Guariglia, Roberto ;
Buda, Gabriele ;
Stelitano, Caterina ;
Sacchi, Stefano .
ACTA HAEMATOLOGICA, 2017, 137 (01) :7-14
[3]   CD30 Downregulation, MMAE Resistance, and MDR1 Upregulation Are All Associated with Resistance to Brentuximab Vedotin [J].
Chen, Robert ;
Hou, Jessie ;
Newman, Edward ;
Kim, Young ;
Donohue, Cecile ;
Liu, Xueli ;
Thomas, Sandra H. ;
Forman, Stephen J. ;
Kane, Susan E. .
MOLECULAR CANCER THERAPEUTICS, 2015, 14 (06) :1376-1384
[4]   Revised response criteria for malignant lymphoma [J].
Cheson, Bruce D. ;
Pfistner, Beate ;
Juweid, Malik E. ;
Gascoyne, Randy D. ;
Specht, Lena ;
Horning, Sandra J. ;
Coiffier, Bertrand ;
Fisher, Richard I. ;
Hagenbeek, Anton ;
Zucca, Emanuele ;
Rosen, Steven T. ;
Stroobants, Sigrid ;
Lister, T. Andrew ;
Hoppe, Richard T. ;
Dreyling, Martin ;
Tobinai, Kensei ;
Vose, Julie M. ;
Connors, Joseph M. ;
Federico, Massimo ;
Diehl, Volker .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (05) :579-586
[5]   A phase II, single-arm, multicentre study of coltuximab ravtansine (SAR3419) and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma [J].
Coiffier, Bertrand ;
Thieblemont, Catherine ;
de Guibert, Sophie ;
Dupuis, Jehan ;
Ribrag, Vincent ;
Bouabdallah, Reda ;
Morschhauser, Franck ;
Navarro, Robert ;
Le Gouill, Steven ;
Haioun, Corinne ;
Houot, Roch ;
Casasnovas, Olivier ;
Holte, Harald ;
Lamy, Thierry ;
Broussais, Florence ;
Payrard, Sandrine ;
Hatteville, Laurence ;
Tilly, Herve .
BRITISH JOURNAL OF HAEMATOLOGY, 2016, 173 (05) :722-730
[6]   Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study [J].
Crump, Michael ;
Neelapu, Sattva S. ;
Farooq, Umar ;
Van den Neste, Eric ;
Kuruvilla, John ;
Westin, Jason ;
Link, Brian K. ;
Hay, Annette ;
Cerhan, James R. ;
Zhu, Liting ;
Boussetta, Sami ;
Feng, Lei ;
Maurer, Matthew J. ;
Navale, Lynn ;
Wiezorek, Jeff ;
Go, William Y. ;
Gisselbrecht, Christian .
BLOOD, 2017, 130 (16) :1800-1808
[7]   Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma [J].
Dang, Nam H. ;
Ogura, Michinori ;
Castaigne, Sylvie ;
Fayad, Luis E. ;
Jerkeman, Mats ;
Radford, John ;
Pezzutto, Antonio ;
Bondarenko, Igor ;
Stewart, Douglas A. ;
Shnaidman, Michael ;
Sullivan, Sharon ;
Vandendries, Erik ;
Tobinai, Kensei ;
Ramchandren, Radhakrishnan ;
Hamlin, Paul A. ;
Gine, Eva ;
Ando, Kiyoshi .
BRITISH JOURNAL OF HAEMATOLOGY, 2018, 182 (04) :583-586
[8]   Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma [J].
Dornan, David ;
Bennett, Fiona ;
Chen, Yvonne ;
Dennis, Mark ;
Eaton, Dan ;
Elkins, Kristi ;
French, Dorothy ;
Go, Mary Ann T. ;
Jack, Andrew ;
Junutula, Jagath R. ;
Koeppen, Hartmut ;
Lau, Jeffrey ;
McBride, Jacqueline ;
Rawstron, Andy ;
Shi, Xiaoyan ;
Yu, Nancy ;
Yu, Shang-Fan ;
Yue, Peng ;
Zheng, Bing ;
Ebens, Allen ;
Polson, Andrew G. .
BLOOD, 2009, 114 (13) :2721-2729
[9]   Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in Relapsed or Refractory Indolent Lymphoma [J].
Dreyling, Martin ;
Santoro, Armando ;
Mollica, Luigina ;
Leppa, Sirpa ;
Follows, George A. ;
Lenz, Georg ;
Kim, Won Seog ;
Nagler, Arnon ;
Panayiotidis, Panayiotis ;
Demeter, Judit ;
Ozcan, Muhit ;
Kosinova, Marina ;
Bouabdallah, Krimo ;
Morschhauser, Franck ;
Stevens, Don A. ;
Trevarthen, David ;
Giurescu, Marius ;
Cupit, Lisa ;
Liu, Li ;
Koechert, Karl ;
Seidel, Henrik ;
Pena, Carol ;
Yin, Shuxin ;
Hiemeyer, Florian ;
Garcia-Vargas, Jose ;
Childs, Barrett H. ;
Zinzani, Pier Luigi .
JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (35) :3898-+
[10]   Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab [J].
Fayad, Luis ;
Offner, Fritz ;
Smith, Mitchell R. ;
Verhoef, Gregor ;
Johnson, Peter ;
Kaufman, Jonathan L. ;
Rohatiner, Ama ;
Advani, Anjali ;
Foran, James ;
Hess, Georg ;
Coiffier, Bertrand ;
Czuczman, Myron ;
Gine, Eva ;
Durrant, Simon ;
Kneissl, Michelle ;
Luu, Kenneth T. ;
Hua, Steven Y. ;
Boni, Joseph ;
Vandendries, Erik ;
Dang, Nam H. .
JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (05) :573-583