Orelabrutinib Combined With Induction Therapy Followed by Sequential Monotherapy Maintenance in MCD Subtype Diffuse Large B-cell Lymphoma

This is a single-center, single-arm, prospective study aimed at evaluating the efficacy and safety of orelabrutinib combined with an induction regimen followed by monotherapy maintenance in patients with MCD subtype diffuse large B-cell lymphoma (DLBCL).

• R-CHOP+Orelabrutinib (Drug), also known as Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, Orelabrutinib: R-CHOP Regimen Rituximab: 375 mg/m², Day 0 Cyclophosphamide: 750 mg/m², Day 1 Doxorubicin: 50 mg/m², Day 1 Vincristine: 1.4 mg/m², Day 1 (maximum single dose: 2 mg) Prednisone: 100 mg, Days 1-5 Orelabrutinib 150mg QD every 21 days per cycle in Induction therapy, 28 days/cycle during maintenance therapy
• POLA-R-CHP+orelabrutinib (Drug), also known as Rituximab, Vepoliximab, Cyclophosphamide, Doxorubicin, Prednisone, orelabrutinib: POLA-R-CHP+orelabrutinib Rituximab: 375 mg/m², Day 1 Vepoliximab: 1.8 mg/kg, Day 1 Cyclophosphamide: 750 mg/m², Day 1 Doxorubicin: 50 mg/m², Day 1 Prednisone: 100 mg, Days 1-5 orelabrutinib 150mg QD every 21 days per cycle in Induction therapy, 28 days/cycle during maintenance therapy
• R-miniCHOP +orelabrutinib (Drug), also known as Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, orelabrutinib: R-miniCHOP Regimen Rituximab: 375 mg/m², Day 0 Cyclophosphamide: 400 mg/m², Day 1 Doxorubicin: 25 mg/m², Day 1 Vincristine: 1 mg, Day 1 Prednisone: 40 mg/m², Days 1-5 orelabrutinib 150mg QD every 21 days per cycle in Induction therapy, 28 days/cycle during maintenance therapy
• Zuberitamab-CHOP+orelabrutinib (Drug), also known as Zuberitamab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone: Zuberitamab: 375 mg/m², Day 0 Cyclophosphamide: 400 mg/m², Day 1 Doxorubicin: 25 mg/m², Day 1 Vincristine: 1 mg, Day 1 Prednisone: 40 mg/m², Days 1-5 orelabrutinib 150mg QD every 21 days per cycle in Induction therapy, 28 days/cycle during maintenance therapy
• POLA-Hi-CHP+orelabrutinib (Drug), also known as Vepoliximab, Cyclophosphamide, Doxorubicin, Prednisone, orelabrutinib, Zuberitamab: POLA-Hi-CHP+orelabrutinib Zuberitamab: 375 mg/m², Day 1 Vepoliximab: 1.8 mg/kg, Day 1 Cyclophosphamide: 750 mg/m², Day 1 Doxorubicin: 50 mg/m², Day 1 Prednisone: 100 mg, Days 1-5 orelabrutinib 150mg QD every 21 days per cycle in Induction therapy, 28 days/cycle during maintenance therapy
• Hi-miniCHOP +orelabrutinib (Drug), also known as Zuberitamab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone,, orelabrutinib: Hi-miniCHOP Regimen Zuberitamab: 375 mg/m², Day 0 Cyclophosphamide: 400 mg/m², Day 1 Doxorubicin: 25 mg/m², Day 1 Vincristine: 1 mg, Day 1 Prednisone: 40 mg/m², Days 1-5 orelabrutinib 150mg QD every 21 days per cycle in Induction therapy, 28 days/cycle during maintenance therapy
• RMTO (Drug), also known as Rituximab, orelabrutinib, Thiotepa, Methotrexate: RMTO Regimen Rituximab: 375 mg/m², Day 1 Methotrexate: 3.5 g/m², Day 2 Thiotepa 30 mg/m² Day 4 Orelabrutinib: 150 mg, Days 1-21 every 21 days per cycle in Induction therapy, maintenance therapy 28 days/cycle
• HiMTO (Drug), also known as Zuberitamab, orelabrutinib, Thiotepa, Methotrexate: HiMTO Regimen Zuberitamab: 375 mg/m², Day 1 Methotrexate: 3.5 g/m², Day 2 Thiotepa 30 mg/m² Day 4 Orelabrutinib: 150 mg, Days 1-21 every 21 days per cycle in Induction therapy, maintenance therapy 28 days/cycle
• Pola-R-miniCHP+O (Drug), also known as Polatuzumab vedotin, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone: Pola-R-miniCHP Regimen Polatuzumab vedotin: 1.8 mg/kg IV, Day 1 Rituximab: 375 mg/m² IV, Day 1 Cyclophosphamide: 400 mg/m² IV, Day 1 Doxorubicin: 25 mg/m² IV, Day 1 Prednisone: 40 mg/m² PO, Days 1-5 every 21 days per cycle in Induction therapy, maintenance therapy 28 days/cycle
• Pola-Hi-miniCHP (Drug), also known as Polatuzumab vedotin, Cyclophosphamide, Doxorubicin, Prednisone, Zuberitamab, orelabrutinib: Pola-Hi-miniCHP Regimen (21-day cycle, up to 6 cycles) Polatuzumab vedotin: 1.8 mg/kg IV, Day 1 Zuberitamab: 375 mg/m² IV, Day 1 Cyclophosphamide: 400 mg/m² IV, Day 1 Doxorubicin: 25 mg/m² IV, Day 1 Prednisone: 40 mg/m² PO, Days 1-5 every 21 days per cycle in Induction therapy, maintenance therapy 28 days/cycle

Primary outcomes

• 2year PFS [From the start of treatment up to 2 years]: The percentage of subjects who had not experienced disease progression or all-cause death at 24 months from first dose, relative to the total enrolled population.

Secondary outcomes

• ORR [From the start of treatment up to 2 years]: The proportion of patients who achieved a PR or better response at the end of therapy
• CRR [From the start of treatment up to 2 years]: Proportion of patients achieving CR at the end of treatment
• OS [From the start of treatment up to 2 years]: Time from treatment initiation to death from any cause
• AEs [From the start of treatment up to 2 years]: All adverse medical events that occurred after the initiation of treatment

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patients of any gender, aged ≥18 years;
* Pathologically, NGS, and imaging confirmed diagnosis of MCD subtype DLBCL (including IP-LBCLs);
* No prior treatment history;
* Serum creatinine ≤2 times the upper limit of normal or eGFR ≥40 ml/min;
* Bilirubin <1.5 times the upper limit of normal;
* Understand and voluntarily sign a written informed consent form.

Exclusion Criteria:

* Pregnant or lactating women and women of childbearing age who are unwilling to use contraception;
* Patients with a history of stroke or bleeding within the past 6 months;
* Patients requiring treatment with strong CYP3A inhibitors;
* Patients with comorbid autoimmune deficiency diseases or active hepatitis virus infection;
* Patients with a history of organ transplantation;
* Patients with a history of or concurrent other malignant tumors.