Introduction: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma (NHL), accounts for approximately 30% of newly diagnosed NHL, with approximately 150,000 new cases annually worldwide. The median age at diagnosis is around 65 years, with 30% of patients aged > 75. While the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) achieves cure rates of 60%-70%, its anthracycline component (doxorubicin) causes significant cardiotoxicity, precluding its use in patients with pre-existing cardiac dysfunction or cardiovascular risk factors (e.g., coronary artery disease, hypertension, valvular heart disease). Effective alternative regimens are needed for this population. Mitoxantrone hydrochloride liposome (Lipo-MIT), as a modified formulation of the anthracycline drug mitoxantrone, possesses the characteristic of reducing cardiotoxicity.

Aim: This prospective, single-arm, multicenter trial evaluated the safety and efficacy of first-line R-CMOP (rituximab, cyclophosphamide, Lipo-MIT, vincristine, prednisone) or Pola-R-CMP (polatuzumab vedotin, rituximab, cyclophosphamide, Lipo-MIT, prednisone) in newly diagnosed DLBCL patients with cardiac comorbidity or those experiencing cardiac adverse events (AEs) after 1-3 cycles of R-CHOP. This study has been registered (NCT05777369) at www.clinicaltrials.gov.

Methods: Eligible adults had newly diagnosed DLBCL with cardiac comorbidity defined as: left ventricular ejection fraction (LVEF) 50-55% by echocardiography, or LVEF >55% with concomitant cardiovascular disease (left ventricular dilation, controlled arrhythmias, myocarditis, pericarditis, structural heart disease). Patients experiencing cardiac AEs after 1-3 cycles of R-CHOP(-like) therapy were also included. Key criteria: ECOG PS ≤2, adequate organ/marrow function, ≥1 measurable lesion. Patients received R-CMOP or Pola-R-CMP (preferred for IPI≥4 or aaIPI=3) every 3 weeks for up to 6 cycles (including prior R-CHOP cycles). Patients aged ≥70 received dose-reduced R-miniCMOP or Pola-R-miniCMP. The primary endpoint was the objective response rate (ORR). Secondary endpoints included complete response rate(CRR), duration of response (DoR), 1-year progression-free survival (PFS), 1-year overall survival (OS), and safety. Adverse events were graded using National Cancer Institute Common Terminology Criteria for Adverse Events ( NCI -CTCAE) v5.0.

Results： Between June 1, 2023, and July 24, 2025, 14 eligible DLBCL patients (median age 73 years, range 53-82; 71.4% male) received R-CMOP or Pola-R-(mini)CMP regimen treatment. 5 (35.7%) patients had received 1-3 prior R-CHOP cycles. One patient had LVEF of 52% and 13 had cardiovascular diseases. All 12 patients were efficacy-evaluable, achieving an ORR of 83.3% (10/12) and CRR of 58.3% (7/12). The CRR and ORR of patients receiving R-CMOP regimen were both 66.7% (2/3) with a median dose of 13.8 mg/m²; while patients receiving R-miniCMOP or Pola-R-miniCMP regimen had a CRR of 55.6% (5/9) and ORR of 88.9% (8/9) with a median dose of 6.4 mg/m². At a median follow-up of 5.4 months, both median PFS, OS and DoR were not mature. Grade 3/4 treatment-related adverse events were hematological adverse events, and the overall safety was controllable. One patient experienced QTc interval prolongation of grade 3 on the electrocardiogram, but relieved after treatment. No new/worsening abnormalities in cardiac biomarkers (cTnT, CK-MB, BNP), or left ventricular function were observed post-treatment.

Conclusion:First-line R-CMOP and Pola-R-CMP regimens demonstrated manageable safety and promising efficacy in DLBCL patients with cardiac comorbidities, without increased cardiotoxicity risk. This study is ongoing and updated results will be presented in the future.

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2025
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