R-Cmop and Pola-R-CMP Regimes As First-Line Treatment for Diffuse Large B-Cell Lymphoma with Cardiac Comorbidity

Introduction:

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for approximately 30% of all newly diagnosed NHL patients. Globally, there are approximately 150,000 new patients of DLBCL diagnosed each year. The median age at diagnosis for DLBCL patients is around 65 years, with 30% of patients being over the age of 75. For several decades, the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the backbone of DLBCL treatment, achieving overall cure rates in the range of 60% to 70%. However, due to the cardiotoxicity associated with doxorubicin, patients with compromised cardiac function cannot receive R-CHOP therapy. Additionally, the risk of cardiotoxicity increases in patients with cardiovascular risk factors such as a history of coronary artery disease, hypertension, or valvular heart disease. Therefore, there is a need for a novel treatment approach for these patients.

Aims:

The study was a prospective, single-arm, multicenter clinical trial to evaluate the safety and efficacy of R-CMOP (rituximab, cyclophosphamide, mitoxantrone hydrochloride liposome, vincristine, prednisone) or Pola-R-CMP (polatuzumab vedotin, rituximab, cyclophosphamide, mitoxantrone hydrochloride liposome, prednisone) regimes as first-line therapy for newly diagnosed DLBCL with cardiac comorbidity or in whom cardiac adverse events happened after 1-3 cycles R-CHOP treatment.

Methods:

Adult patients with newly diagnosed DLBCL with cardiac comorbidity or in whom cardiac adverse events happened after 1-3 cycles R-CHOP treatment. ECOG performance status ≤2, normal organ and bone marrow function, and at least one measurable or evaluable lesion were enrolled in this study. R-CMOP or Pola-R-CMP (suitable for patients with IPI≥4 or aaIPI=3) regimen was administered every 3 weeks for up to 6 cycles until disease progression or an intolerable toxic. For those who have received 1-3 cycles R-CHOP treatment, the overall cycles of treatment is 6. 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) 5.0.

Results：

From 1 June , 2023 through 4 June, 2024. 7 Chinese patients with DLBCL who were eligible for enrollment were treated with the R-CMOP or Pola-R-CMP regimen. The median age of the patients was 70 years (range, 57 to 72), with 71.4% being male. 3 patients had received 1-3 cycles of R-CHOP prior to enrolment. 7 patients were evaluated for efficacy, showing an ORR of 100% and a CRR of 85.7% . The most common grade 3/4 TRAEs with an incidence of ≥20% were lymphopenia (57.1%), anemia (57.1%), leucopenia (42.9%), fever (28.6%), neutropenia (28.6%), pneumonia(28.6%). There was no newly found or aggravated cTnT, CK-MB, BNP value abnormality, QTC abnormality and lower LV function after medication.

Conclusion:

CMOP and Pola-R-CMP regimens as first-line treatment for Diffuse Large B-Cell Lymphoma with cardiac comorbidity exhibited manageable safety and encouraging efficacy without an increased risk of cardiotoxicity.This study is ongoing and updated results will be presented in the future.

No relevant conflicts of interest to declare.