Lorenzo Tonialini

Interesting activity of pegylated liposomal doxorubicin in primary refractory and multirelapsed Hodgkin lymphoma patients: bridge to transplant

Most patients with classical Hodgkin lymphoma (cHL) can be cured with frontline therapy, and those with relapsed or refractory (R/R) disease can often be cured with salvage therapy and autologous stem cell transplantation (ASCT). However, the prognosis of patients who relapse after or are ineligible to ASCT has historically been extremely poor, with a median overall survival of just over 2 years. Achieving durable responses in this patient population is a critical treatment goal so far only rarely achieved with conventional chemotherapy. Brentuximab vedotin (BV) has demonstrated efficacy in patients treated after failure of ASCT, with objective responses seen in 75% of patients in a phase 2 study. Recently, because of the unique genetics of cHL, the check point inhibitors nivolumab and pembrolizumab were tested in phase 1 to 2 studies that demonstrated objective responses in 70% to 85% heavily pretreated patients with R/R cHL. Among the different conventional salvage chemotherapy regimens and conventional single agents, such as bendamustine, BV, nivolumab, and pembrolizumab, there is another drug with interesting results in the setting of R/R cHL, but less known and used: the pegylated liposomal doxorubicin (PLD). It is a new formulation of doxorubicin in which the drug is encapsulated in liposomes and stabilized by the attachment of polyethylene glycol (ie, pegylation) to the liposomal surface, resulting in increased half‐life and improved accumulation in tumor tissues. Its toxicity profile is characterized by dose‐limiting mucosal and cutaneous adverse effects, in particular palmo‐plantar erythrodysesthesia syndrome, reported in up to 20% of treated patients. In addition, PLD presents a reduced cardiac toxicity compared to nonliposomal doxorubicin; it has shown efficacy alone and in combination in multirelapsed cHL. Clozel et al reported the only published data on the role of PLD as single agent in R/R cHL patients: in a subset of 23 patients the authors observed some long‐term remissions and 6 patients were treated again for later relapses. Here we report results of a single‐center experience on the role of PLD in monotherapy in the treatment of heavily pretreated refractory HL patients. Nine patients with R/R HL were treated at our institution from April 2014 to July 2017. The median age at treatment was 37 years (range 21‐57 y). All patients were heavily pretreated and refractory to the last regimen; the median count of previous regimens

Siltuximab in relapsed/refractory multicentric Castleman disease: Experience of the Italian NPP program

Because of the rarity of the disease, randomized clinical trials for multicentric Castleman disease (MCD) remain a challenge and, as a consequence, there is no established standard of care. Siltuximab is a chimeric immunoglobulin G1κ monoclonal antibody against human IL‐6 which was recently approved by FDA. Eligible patients in Italy were granted early access through a Named Patient Program (NPP). The aim of this observational multicenter retrospective study was to analyze outcomes and toxicity data of relapsed or refractory MCD patients treated with siltuximab in a real life context. All the 9 patients who received siltuximab in Italy under the NPP were enrolled. Median duration of treatment was 285 days (range, 104‐1113 days). The global overall response rate was 33.3%. At the time of this analysis, none of the 3 responder patients had subsequently disease relapse: response duration was 20, 23, and 37 months, respectively. Grade 1 to 2 fatigue and pruritus were observed in 2 (22.2%) patients, and weight gain was reported in only 1 patient (grade 1); local edema was reported in 2 patients with a grade 2 presentation. The most common side effect was upper respiratory tract infection reported in 3 (33.3%) patients but in these cases was grades 1 to 2. No patient developed an infusion‐related reaction. Our NPP data support siltuximab as single agent in the real‐life experience of the treatment of relapse/refractory MCD patients in effectiveness, safety profile, and sustained disease control.

The Berlin-Frankfurt-Münster protocol for the upfront treatment of aggressive lymphomas: The Bologna experience

criminate between high versus low-risk VTE patients. The benefit of low-molecular weight heparin (LMWH) thromboprophylaxis in patients with a score >=3 has recently been demonstrated. Two ongoing trials, CASSINI with rivaroxaban and AVERT with apixaban are seeking to expand upon this with a cutoff score of >=2, using more patient-friendly direct oral anticoagulants. There are inherent limitations of the current study. First, the NEDS database is administrative data. The initial clinical symptoms leading to ED visits were unavailable which prevented more granular analysis (for instance, ED visits for VTE related symptoms vs. incidental VTE diagnosis during ED visits). Second, VTE diagnosis was only based on ICD-9 codes and coding errors could exist. Third, detailed cancer stages and cancer treatment data were unavailable, which are important predictors for VTE. In summary, VTE diagnosis in cancer patients were associated with higher hospital admission rate, mortality rate, and higher hospital costs and is a significant burden to the healthcare system. Outpatient thromboprophylaxis has the potential to reduce such events, thereby reducing ED visits and associated healthcare resource utilization.