A Prospective, Single-Center Study Evaluating the Efficacy and Safety of Glofitamab Combined With Orelabrutinib and Bortezomib in Patients With High-Risk Mantle Cell Lymphoma

A Prospective, Single-Center Study Evaluating the Efficacy and Safety of Glofitamab Combined With Orelabrutinib and Bortezomib in Patients With High-Risk Mantle Cell Lymphoma

The aim of this study is to evaluate the efficacy and safety of Glofitamab combined with Orelabrutinib and Bortezomib in patients with high-risk mantle cell lymphoma

Inclusion Criteria:

• Signed Informed Consent Form
• Age ≥ 18 years at the time of signing Informed Consent Form and willingness to comply with study protocol procedures
• Participants with MCL
• Meets any of the following high-risk criteria: blastoid/pleomorphic morphology; high Ki-67 (≥ 30%); TP53 aberration; del(17p); complex karyotype; MIPI score ≥ 6.2; early progression after first-line treatment (<24 months); presence of other high-risk genetic mutations (KMT2D, NSD2, NOTCH1, CDKN2A, NOTCH2, SMARCA4, CCND1)
• Life expectancy ≥ 12 weeks
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2
• At least one bi-dimensionally measurable (≥ 1.5 cm) nodal lesion, or one bi-dimensionally measurable (≥ 1 cm) extranodal lesion, as measured on CT scan
• No bone marrow involvement: ANC ≥ 1.0 × 10^9/L; bone marrow involvement: ANC ≥ 0.5 × 10^9/L
• No bone marrow involvement: PLT ≥ 75 × 10^9/L; bone marrow involvement: PLT ≥ 25 × 10^9/L
• No bone marrow involvement: Hgb ≥ 8 g/dL; bone marrow involvement: Hgb ≥ 7 g/dL
• Adequate renal function, defined as measured or estimated creatinine clearance ≥ 30 mL/min

Exclusion Criteria:

• Contraindication to any of the individual components of Glofit-Orela-Borte
• Known active infection at the time of enrollment
• Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HBsAg] serology): Patients with occult or prior HBV infection (defined as negative HbsAg and positive hepatitis B core antibody [HbcAb]) may be included if HBV DNA is undetectable, provided that they are willing to undergo DNA testing on Day 1 of every cycle and every three months for at least 12 months after the last cycle of study treatment and appropriate antiviral therapy
• Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing): Patients who are positive for HCV antibody are eligible only if PCR is negative for HCV RNA
• History of other malignancies that could affect compliance with the protocol or interpretation of results
• Active autoimmune disease requiring treatment
• Primary or secondary CNS lymphoma at the time of recruitment
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications