Brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone as frontline treatment for patients with CD30-positive B-cell lymphomas

Jakub Svoboda, Steven M Bair, Daniel J Landsburg, Sunita Dwivedy Nasta, Sarah J Nagle, Stefan K Barta, Nadia Khan, Joanne Filicko-O'Hara, Sameh Gaballa, Lauren Strelec, Elise Chong, Sheryl Mitnick, Terease S Waite, Cara King, Hatcher Ballard, Matthew Youngman, James Gerson, John P Plastaras, Amit Maity, Agata M Bogusz, Stacy S Hung, Hisae Nakamura, Reza Nejati, Christian Steidl, Megan Lim, Marco Ruella, Stephen J Schuster, Jakub Svoboda, Steven M Bair, Daniel J Landsburg, Sunita Dwivedy Nasta, Sarah J Nagle, Stefan K Barta, Nadia Khan, Joanne Filicko-O'Hara, Sameh Gaballa, Lauren Strelec, Elise Chong, Sheryl Mitnick, Terease S Waite, Cara King, Hatcher Ballard, Matthew Youngman, James Gerson, John P Plastaras, Amit Maity, Agata M Bogusz, Stacy S Hung, Hisae Nakamura, Reza Nejati, Christian Steidl, Megan Lim, Marco Ruella, Stephen J Schuster

Abstract

We conducted a phase I/II multicenter trial using 6 cycles of brentuximab vedotin (BV) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for treatment of patients with CD30-positive (+) B-cell lymphomas. Thirty-one patients were evaluable for toxicity and 29 for efficacy including 22 with primary mediastinal B-cell lymphoma (PMBCL), 5 with diffuse large B-cell lymphoma (DLBCL), and 2 with gray zone lymphoma (GZL). There were no treatment-related deaths; 32% of patients had non-hematological grade 3/4 toxicities. The overall response rate was 100% (95% CI: 88-100) with 86% (95% CI: 68-96) of patients achieving complete response at the end of systemic treatment. Consolidative radiation following end of treatment response assessment was permissible and used in 52% of all patients including 59% of patients with PMBCL. With a median follow-up of 30 months, the 2-year progression-free survival (PFS) and overall survival (OS) were 85% (95% CI: 66-94) and 100%, respectively. In the PMBCL cohort, 2-year PFS was 86% (95% CI: 62-95). In summary, BV-R-CHP with or without consolidative radiation is a feasible and active frontline regimen for CD30+ B-cell lymphomas (NCT01994850).

Figures

Figure 1.
Figure 1.
CONSORT diagram. GZL: gray zone lymphoma; cHL: classical Hodgkin lymphoma; EOT: end of treatment.
Figure 2.
Figure 2.
Survival curves for patients who received the BV-R-CHP treatment regimen. (A, B) Progression-free survival (A) and overall survival (B) of all evaluable patients enrolled in the trial (n=29). (C, D) Progression-free survival (C) and overall survival (D) of evaluable patients with primary mediastinal B-cell lymphoma (PMBCL) (n=22).
Figure 3.
Figure 3.
Examples of different CD30 staining patterns by immunohistochemistry in three representative patients with primary mediastinal B-cell lymphoma enrolled on the trial. (A) Heterogeneous staining pattern with strong and dim staining in different areas of the same tumor. (B) Focal staining in one area of the tumor. (C) Diffuse staining throughout the tumor. The antibodies used were CD20 (ready to use, DAKO) and CD30 (ready to use, Leica) and they were detected using a chromogenic substrate, diaminobenzene (Leica). An original magnification x200 was used for all images. H&E: hematoxylin & eosin.
Figure 4.
Figure 4.
Correlation of Lymph3Cx results with standard clinicopathological diagnoses made by the investigators. DLBCL: diffuse large B-cell lymphoma; GZL: gray zone lymphoma; PMBCL: primary mediastinal B-cell lymphoma. Patients who progressed are labeled by an arrow. Of 14 patients with PMBCL diagnosed by investigator assessment alone, 11 patients (79%) had Lymph3Cx probability scores >0.9, which were consistent with a molecular diagnosis of PMBCL by gene expression analysis, two patients (14%) scored in the indeterminate category (0.1 to 0.9), and one patient (7%) scored as having DLBCL (< 0.1).

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