Atezolizumab combined with immunogenic salvage chemoimmunotherapy in patients with transformed diffuse large B-cell lymphoma

Autor: Tamer Othman, Paul Frankel, Pamela Allen, Leslie L. Popplewell, Geoffrey Shouse, Tanya Siddiqi, Alexey V. Danilov, Nora Ruel, Shari Daniels, Lacolle Peters, Stella Khoo, Steven T. Rosen, Elad Sharon, Miguel Villalona-Calero, Christopher Ruel, Joseph Tuscano, Alex F. Herrera
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Haematologica, Vol 999, Iss 1 (2024)
Druh dokumentu: article
ISSN: 0390-6078
1592-8721
DOI: 10.3324/haematol.2024.285185
Popis: Patients with relapsed/refractory (R/R) transformed diffuse large B-cell lymphoma (DLBCL) from indolent B-cell lymphomas, including Richter transformation (RT), have a poor prognosis. PD-1/PD-L1 antibodies produce modest objective and complete response rates (ORR and CRR) in B-NHL as monotherapy but may synergize with immunogenic chemotherapies like gemcitabine and oxaliplatin (GemOx). Thus, we evaluated the safety and efficacy of atezolizumab plus rituximab and GemOx (R-GemOx+Atezo) in R/R transformed DLBCL, including RT. We conducted a phase I trial including patients with transformed DLBCL after ≥1 prior therapy. Patients received up to 4 cycles of R-GemOx-+Atezo. Patients in CR could then proceed to Ratezo maintenance until progression. A safety lead-in with dose-limiting toxicity (DLT) evaluation was enrolled to confirm the recommended phase 2 dose (RP2D), followed by 2 expansion cohorts: one for transformed follicular lymphoma (FL) and another for non-FL transformed DLBCL, including RT. Twenty-seven patients were enrolled. One of the 6 safety lead-in patients had a DLT attributed to atezolizumab, a grade 4 Stevens-Johnson syndrome (SJS). The most common grade ≥3 events were neutropenia (18.5%), lymphopenia (18.5%), and thrombocytopenia (14.8%). The overall and complete response rates (ORR and CRR) were 59% and 33%, respectively. The ORR and CRR in transformed FL were 79% and 43%, and 38% and 23% in transformed non-FL, respectively. The median PFS and OS of the total population were 4.2 and 7.7 months, respectively. R-GemOx+Atezo was well tolerated and demonstrated promising preliminary efficacy in patients with R/R transformed DLBCL.
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