Liposomal doxorubicin supercharge-containing front-line treatment in patients with advanced-stage diffuse large B-cell lymphoma or classical Hodgkin lymphoma: Preliminary results of a single-centre phase II study

Abstract

We evaluated the impact of liposomal doxorubicin (NPLD) supercharge-containing therapy on interim fluorodeoxyglucose positron emission tomography (interim-FDG-PET) responses in high-risk diffuse large B-cell lymphoma (DLBCL) or classical Hodgkin lymphoma (c-HL). In this phase II study (2016-2021), 81 adult patients with advanced-stage DLBCL (n = 53) and c-HL (n = 28) received front-line treatment with R-COMP-dose-intensified (DI) and MBVD-DI. R-COMP-DI consisted of 70 mg/m² of NPLD plus standard rituximab, cyclophosphamide, vincristine and prednisone for three cycles (followed by three cycles with NPLD de-escalated at 50 mg/m² ); MBVD-DI consisted of 35 mg/m² of NPLD plus standard bleomycin, vinblastine and dacarbazine for two cycles (followed by four 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, 72/81 patients (one failed to undergo interim-FDG-PET due to early death) had a Deauville score of ≤3. At end of treatment, 90% of patients reached complete responses. In all, 20 patients had Grade ≥3 adverse events, and four of them required hospitalisation. 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.

Keywords: DLBCL; R-COMP and MBVD; c-HL; high-dose non-pegylated liposomal doxorubicin.

FIGURE 1

Flow of participants. Ann Arbor Stage III: defined as multiple lymph node groups on both sides of the diaphragm. Ann Arbor Stage IV: defined as multiple extra‐nodal sites or lymph nodes and extra‐nodal disease. DLBCL, diffuse large B‐cell lymphoma; c‐HL, classical Hodgkin lymphoma; ECOG PS, Eastern Cooperative Group Performance Status; R‐COMP‐DI, rituximab, cyclophosphamide, vincristine, Myocet™, prednisone, dose‐intensified; MBVD‐DI, Myocet™, bleomycin, vinblastine, dacarbazine, dose‐intensified; i‐PET, interim 2‐deoxy‐2[F‐18] fluoro‐D‐glucose positron emission tomography; EoT, end‐of‐treatment. Score 4: Deauville scale scoring system showing uptake moderately >liver at FDG‐PET scans. Score 5: Deauville scale scoring system showing uptake markedly increased than liver and/or new lesions at FDG‐PET scans.

FIGURE 2

Percentage variations in left ventricular ejection fraction (EF) (A) and global systolic longitudinal myocardial strain (GLS) (B) throughout treatment up to 6 months after completion of study treatments expressed in individual values. EOT, end of treatment.

FIGURE 3

Progression‐free survival (PFS). Kaplan–Meier curve of 21‐month PFS of 81 patients with advanced‐stage diffuse large B‐cell lymphoma (DLBCL) and classical Hodgkin lymphoma (c‐HL) who received the liposomal doxorubicin supercharge‐based front‐line strategy (A), PFS for patients with DLBCL (n = 53) (B), and for patients with c‐HL (n = 28) (C). PFS for patients (n = 46) with specific extra‐nodal sites involved (i.e. spleen, lung, bone and/or liver) versus the remaining patients with only nodal (n = 19) and nodal with other extra‐nodal sites involved (n = 16) (D). Figures also show number of events and number at risk during follow‐up.