Liposomal doxorubicin supercharge‐containing frontline treatment for diffuse large B‐cell lymphoma or classical Hodgkin lymphoma: preliminary results of a phase II study

Myocet™ is doxorubicin encapsulated in a non-pegylated liposomal membrane of phosphatidylcholine and cholesterol (NPLD) that spares the heart muscle from the direct cytotoxic drug. NPLD was suggested for the treatment of elderly or cardiopathic patients with DLBCL or c-HL, instead of hydroxydaunorubicin, constituting new regimens of R-COMP (Rituximab, cyclophosphamide, NPLD and vincristine) and MBVD (NPLD, bleomycin, vinblastine and dacarbazine) respectively. We designed a dose-intensified (DI) version of both R-COMP and MBVD scheme by using a supercharge dose of NPLD (named R-COMP-DI and MBVD-DI). In this prospective study, patients with newly diagnosed advanced-stage DLBCL received R-COMP-DI for a total of 3 cycles followed by 3 cycles of R-COMP (with NPLD at standard dose), and patients with newly diagnosed advanced-stage c-HL received MBVD-DI for a total of 2 cycles followed by 4 cycles of MBVD (with NPLD at standard dose). The primary end-point was the activity of this strategy in terms of interim-FDG-PET negativity (according to the Deauville scale [DS] 5-point scoring system). Secondary end-points were end-of-treatment (EoT) responses, toxicity (including cardiologic side-effects by using the echocardiography [ECG] assessment of global systolic longitudinal myocardial strain [GLS], as well as left ventricular ejection fraction [LVEF]), feasibility and Progression Free survival (PFS). In this phase II study (2016–2022), 92 adult patients, admitted to the Federico II Hematology Department, with advanced-stage DLBCL (n = 60) and c-HL (n = 32) received front-line R-COMP-DI and MBVD-DI. In R-COMP-DI, 70 mg/m2 of NPLD was employed for 3 cycles (followed by 3 cycles with NPLD de-escalated at 50 mg/m2); MBVD-DI consisted of 35 mg/m2 of NPLD for 2 cycles (followed by 4 cycles with NPLD de-escalated at 25 mg/m2). Patients underwent R-COMP-DI and MBVD-DI with a median dose intensity of 91% and 94%, respectively. At interim-FDG-PET, 81/92 patients (one failed to undergo interim-FDG-PET due to early death) had a Deauville score of ≤3 reaching the primary end-point of the trial in terms of complete response incidence at interim imaging assessment with a Complete Metabolic response rate significantly higher (89% [95% CI: 83%–96%]; p = 0.0015) than the pre-specified minimum efficacy threshold. At end of treatment, 90% of patients reached complete responses. In all, 20 patients had Grade ≥3 adverse events, and four of them required hospitalization. According to the definition of cardiotoxicity for cancer treatment of ESC, there were very small changes, i.e. <10% point reductions in median values of GLS and LVEF at interim, EoT and 6-month follow-up, when they were compared with the median values at baseline. At a median 21-months of follow-up, the progression-free survival of the entire population was 77.3% (95% confidence interval 68%–88%). Our data suggest that the NPLD supercharge-driven strategy in high-risk DLBCL/c-HL may be a promising option to test in phase III trials, for improving negative interim-FDG-PET cases incidence. Keyword: Chemotherapy No conflicts of interests pertinent to the abstract.