Liposomal Doxorubicin, Vinblastine and Dacarbazine Plus Consolidation Radiotherapy of Residual Nodal Masses for Frontline Treatment in Older Adults With Advanced Stage Classic Hodgkin Lymphoma: Improved Outcome in a Multi-Center Real-Life Study

Abstract

In elderly patients with high-risk classic Hodgkin lymphoma (c-HL), we evaluated the impact of a new modality treatment without bleomycin, that is, liposomal doxorubicin (NPLD)-based regimen plus consolidation radiotherapy of residual nodal masses (RNMs), on overall survival (OS) and progression free survival (PFS). In this retrospective study (2013-2023) conducted in tertiary hospitals in the bay of Naples (Italy), 50 older adults (median age, 69 years; range, 60-89) with advanced stage c-HL received frontline treatment with MVD ± irradiation. MVD consisted of 25 mg/m² of NPLD along with standard Vinblastine and Dacarbazine for a total of 6 cycles (twelve iv administrations, every 2 weeks) followed by radiation of RNMs with size ≥ 2.5 cm at computed tomography. Patients underwent MVD with a median dose intensity of 92%. At 2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography (FDG-PET), 90% of patients (45/50 patients; one failed to perform final FDG-PET due to early death) reached complete responses. Altogether, 17 patients (34%) received consolidation radiotherapy of RNMs with Deauville score ≥ 3. At 5-year median follow-up, the OS and PFS of the entire population were 87.5% (95% confidence interval [CI], 78.7-97.4) and 81.6% (95% CI, 71.4-93.2), respectively. Eleven patients (22%) experienced grade ≥ 3 adverse events, and 4 of them required hospitalization. Our data suggest that in older adults with high-risk c-HL NPLD-driven strategy (without bleomycin) plus consolidation radiotherapy (if needed) may be a promising up-front option, to test in phase II clinical trials for improving survival incidence.

Keywords: MVD; consolidation radiotherapy; c‐HL; elderly patients; non‐pegylated liposomal doxorubicin.

FIGURE 1

Drug doses, schedule, and treatment administration details of frontline MVD regimen ± irradiation. Dose‐intensity and dose‐dense of non‐pegylated liposomal doxorubicin in cycles 1‐6 for MVD, and diagnostic work‐up and vigorous support treatments are also shown. FDG‐PET/CT, 2‐deoxy‐2[F‐18] fluoro‐D‐glucose positron emission tomography/computed tomography; MVD, Myocet, Vinblastine, Dacarbazine.

FIGURE 2

Flow of participants. DS, Deauville scale scoring system; FDG‐PET/CT, 2‐deoxy‐2[F‐18] fluoro‐D‐glucose positron emission tomography/computed tomography; MVD, myocet, vinblastine, dacarbazine.

FIGURE 3

(A–C) Overall survival (OS) and Progression free survival (PFS). Kaplan Meier curves of 60 months OS and PFS (A and B, respectively) of 50 elderly patients with advanced stage classic Hodgkin lymphoma (c HL) who received the liposomal doxorubicin based (without bleomycin) frontline strategy ± irradiation. OS for elderly patients with c HL (n= 50) according to age stratification: 60‐69 years (n= 27) vs. 70‐79 years (n= 17) vs. ≥ 80 years (n= 6) (C). Figures also show the number of events and the number at risk during follow up.

FIGURE 4

(A, B) Percentage variations in global systolic longitudinal myocardial strain (GLS) (A) and left ventricular ejection fraction (LVEF) (B) and throughout treatment up to 6‐month after completion of study treatments expressed in individual values. Shaded areas represent abnormal values of echocardiographic measurements. The bold curve represents the median values at all time points.