Polatuzumab vedotin, venetoclax, and an anti‐CD20 monoclonal antibody in relapsed/refractory B‐cell non‐Hodgkin lymphoma

• Published in: American journal of hematology 2024-07, Vol.99 (7), p.1281-1289
• Main Authors: Yuen, Sam, Phillips, Tycel J., Bannerji, Rajat, Marlton, Paula, Gritti, Giuseppe, Seymour, John F., Johnston, Anna, Arthur, Christopher, Dodero, Anna, Sharma, Sunil, Hirata, Jamie, Musick, Lisa, Flowers, Christopher R.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bridged Bicyclo Compounds, Heterocyclic - administration & dosage; Bridged Bicyclo Compounds, Heterocyclic - adverse effects; Bridged Bicyclo Compounds, Heterocyclic - therapeutic use; CD20 antigen; Diarrhea; Female; Humans; Immunoconjugates; Induction therapy; Lymphoma; Lymphoma, Follicular - drug therapy; Lymphoma, Large B-Cell, Diffuse - drug therapy; Male; Middle Aged; Monoclonal antibodies; Neutropenia; Non-Hodgkin's lymphoma; Recurrence; Rituximab; Rituximab - administration & dosage; Rituximab - adverse effects; Rituximab - therapeutic use; Safety; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Targeted cancer therapy; Toxicity
• ISSN: 0361-8609; 1096-8652; 1096-8652
• DOI: 10.1002/ajh.27341

The Phase 2 portion of this study evaluated safety and efficacy of polatuzumab vedotin 1.8 mg/kg and venetoclax 800 mg, plus fixed‐dose obinutuzumab 1000 mg or rituximab 375 mg/m2 in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or diffuse large B‐cell lymphoma (DLBCL), respectively. Patients with complete response (CR) or partial response (PR)/stable disease (FL) or CR/PR (DLBCL) at end of induction (EOI; six 21‐day cycles) received post‐induction therapy with venetoclax and obinutuzumab or rituximab, respectively. Primary endpoint was CR rate at EOI. Safety‐evaluable populations included 74 patients (FL cohort; median age 64 years; progression of disease within 24 months on first‐line treatment, 25.7%; FL International Prognostic Index 3–5, 54.1%; ≥2 previous therapies, 74.3%) and 57 patients (DLBCL cohort; median age 65 years; International Prognostic Index 3–5, 54.4%; ≥2 previous therapies, 77.2%). The most common non‐hematologic adverse events (mostly Grades 1–2) in the FL and DLBCL cohorts were diarrhea (55.4% and 47.4%, respectively) and nausea (47.3% and 36.8%); neutropenia was the most common Grades 3–4 toxicity (39.2% and 52.6%). Efficacy‐evaluable populations included patients treated at the recommended Phase 2 dose (FL, n = 49; DLBCL, n = 48). CR rates at EOI were 59.2% (FL) and 31.3% (DLBCL); median progression‐free survival was 22.8 months (95% confidence interval [CI], 14.5—not evaluable) and 4.6 months (95% CI, 3.6–8.1), respectively. Polatuzumab vedotin plus venetoclax and obinutuzumab/rituximab had acceptable safety in patients with R/R FL or DLBCL, with promising response rates in R/R FL, including high‐risk patients.