Incidence of cancer treatment-related cardiotoxicity in patients with lymphoma treated with non-pegylated liposomal doxorubicin

Background Anthracyclines are a cornerstone of first-line treatment of lymphoma, but are burdened by cancer treatment-related cardiovascular toxicity (CTR-CVT), which is particularly relevant in patients with advanced age or pre-existing cardiac disease. The risk of CVT is mitigated by the use of non-pegylated liposomal doxorubicin (NPLD). Purpose To assess the outcomes of patients who received NPLD for non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). Methods We retrospectively collected clinical, echocardiographic, and outcome data of patients with newly diagnosed or relapsed NHL/HL, who had been treated with NPLD and then followed at our institution between Jan. 1st, 2007 and Dec. 31st, 2023. The risk of CTR-CVT was evaluated at baseline as recommended by the Heart Failure Association (HFA) and International Cardio-oncology Society (ICOS). CTR-CVT included development of left ventricular dysfunction (LVD), new-onset or worsening heart failure (HF), and acute coronary syndrome (ACS) during follow-up. Baseline characteristics were compared by chi-square test, t-test, or Mann-Whitney test, as appropriate. The Kaplan-Meier method was used to assess CTR-CVT and progression-free survival (PFS). Results Of a total of 199 patients during the study period, 127 (63.8%) had diffuse large cell lymphoma (DLBCL), 43 (21.6%) indolent NHL, 14 (7%) HL, and 15 (7.5%) T-cell lymphoma. The median age at diagnosis was 73 (66-78) years and 112 (56.2%) were male. The reasons for treatment with NPLD were old age (N=119, 59.7%), pre-existing cardiac disease (N=35, 17.5%), participation in a clinical trial (N=32, 16.1%), and previous anthracycline therapy (N=13, 6.5%). At baseline, 5 (2.5%) patients had a very high HFA-ICOS risk profile, 84 (42.2%) were at high risk, and 80 (40.2%) were at intermediate risk. NPLD was completed in 169 (85%) patients and CTR-CVT occurred in 24 (12%): 1 (0.5%) had LVD, 16 (8%) HF, and 7 (3.51%) ACS. The median onset time of HF (9.1 [3.3-22.7] months) was shorter than that of ACS (32.1 [19.4-43.6] months). CTR-CVT was significantly more likely in patients older than 75 years (Fig. 1A) and in those with very high or high HFA-ICOS risk estimate (Fig. 1B). Overall, 67 (33.6%) patients died, because of lymphoma progression (38 [56.7%)], infection (17 [25.3%]), secondary neoplasm (1 [1.49%]), or unknown causes (11 [16.4%]). No death was attributed to CTR-CVT. Facing CTR-CVT was not associated with worse PFS (Fig. 1C). Conclusions Our findings confirm a favorable balance between feasibility, effectiveness, and CV safety of NPLD-containing chemotherapy for lymphoma. The HFA-ICOS approach well stratified the risk of CTR-CVT. Although the incidence of the latter was sizable in our cohort, it did not affect cancer outcomes and mortality from any cause.Figure 1