Lenalidomide-based induction and maintenance in elderly newly diagnosed multiple myeloma patients: updated results of the EMN01 randomized trial

In the EMN01 trial, the addition of an alkylator (melphalan or cyclophosphamide) to lenalidomide-steroid induction has been prospectively evaluated in transplant-ineligible multiple myeloma patients. After induction, patients were randomly assigned to maintenance treatment with lenalidomide alone or with prednisone continuously. This analysis (median follow-up of 71 months) focused on maintenance treatment and on subgroup analyses according to the International Myeloma Working Group Frailty Score. 217 patients in lenalidomide-dexamethasone, 217 in melphalan-prednisone-lenalidomide and 220 in cyclophosphamide-prednisone-lenalidomide arms were evaluable. 284 (43%) patients were fit, 205 (31%) intermediate-fit and 165 (25%) frail. After induction, 402 patients were eligible for maintenance, (lenalidomide arm: 204; lenalidomide-prednisone: 198). After a median duration of maintenance of 22.0 months, progression-free survival from start of maintenance was 22.2 months with lenalidomide-prednisone vs 18.6 months with lenalidomide (HR 0.85,p=0.14), with no differences across frailty subgroups. The most frequent grade ≥3 toxicity was neutropenia (10% of lenalidomide-prednisone and 21% of lenalidomide patients; p=0.001). Grade ≥3 non-hematologic adverse events were rare (<15%). In fit patients, melphalan-prednisone-lenalidomide significantly prolonged progression-free survival compared to cyclophosphamide-prednisone-lenalidomide (HR 0.72,p=0.05) and lenalidomide-dexamethasone (HR 0.72, p=0.04). Likewise, a trend towards a better overall survival was noted for melphalan-prednisone-lenalidomide and cyclophosphamide-prednisone-lenalidomide, as compared to lenalidomide-dexamethasone. No differences were observed in intermediate-fit and frail patients. This analysis showed positive outcomes of maintenance with lenalidomide-based regimens, with a good safety profile. For the first time, we showed that fit patients benefit from a triplet full-dose regimen, while intermediate-fit and frail patients from gentler regimens. ClinicalTrials.gov registration number: NCT01093196

Ante situm liver resection with inferior vena cava replacement under hypothermic cardiopolmunary bypass for hepatoblastoma: Report of a case and review of the literature

Introduction: Hepatoblastoma with tumour thrombi extending into inferior-vena-cava and right atrium are often unresectable with an extremely poor prognosis. The surgical approach is technically challenging and might require major liver resection with vascular reconstruction and extracorporeal circulation. However, which is the best surgical technique is yet unclear. Presentation of case: A 11-months-old boy was referred for a right hepatic lobe mass(90 × 78 mm) suspicious of hepatoblastoma with tumoral thrombi extending into the inferior-vena-cava and the right atrium, bilateral lung lesions and serum alpha-fetoprotein level of 50.795 IU/mL. After 8 months of chemotherapy (SIOPEL 2004-high-risk-Protocol), the lung lesions were no longer clearly visible and the hepatoblastoma size decreased to 61 × 64 mm. Thus, ante situm liver resection was planned: after hepatic parenchymal transection, hypothermic cardiopulmonary bypass was started and en bloc resection of the extended-right hepatic lobe, the retro/suprahepatic cava and the tumoral trombi was performed with concomitant cold perfusion of the remnant liver. The inferior-vena-cava was replaced with an aortic graft from a blood-group compatible cadaveric donor. The post-operative course was uneventful and after 8 months of follow-up the child has normal liver function and an alpha-fetoprotein level and is free of disease recurrence with patent vascular graft. Conclusions: We report for the first time a case of ante situ liver resection and inferior-vena-cava replacement associated with hypothermic cardiopulmonary bypass in a child with hepatoblastoma. Herein, we extensively review the literature for hepatoblastoma with thumoral thrombi and we describe the technical aspects of ante situm approach, which is a realistic option in otherwise unresectable hepatoblastoma

Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss

Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research

Impact of influenza vaccination on survival of patients with advanced cancer receiving immune checkpoint inhibitors (INVIDIa-2): final results of the multicentre, prospective, observational study

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration. Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020. The trial's primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020, the results of which were reported previously. Secondary endpoints (data cut-off Jan 31, 2022) included the outcomes of patients to immunotherapy based on vaccine administration, for which the final results are reported herein. A propensity score matching by age, sex, performance status, primary tumour site, comorbidities, and smoking habits was planned for the present analysis. Only patients with available data for these variables were included. The outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease-control rate (DCR). Findings: The original study population consisted of 1188 evaluable patients. After a propensity score matching, 1004 patients were considered (502 vaccinated and 502 unvaccinated), and 986 of them were evaluable for overall survival (OS). At the median follow-up of 20 months, the influenza vaccination demonstrated a favourable impact on the outcome receiving ICI in terms of median OS [27.0 months (CI 19.5-34.6) in vaccinated vs. 20.9 months (16.6-25.2) in unvaccinated, p = 0.003], median progression-free survival [12.5 months (CI 10.4-14.6) vs. 9.6 months (CI 7.9-11.4), p = 0.049], and disease-control rate (74.7% vs. 66.5%, p = 0.005). The multivariable analyses confirmed the favourable impact of influenza vaccination in terms of OS (HR 0.75, 95% C.I. 0.62-0.92; p = 0.005) and DCR (OR 1.47, 95% C.I. 1.11-1.96; p = 0.007). Interpretation: The INVIDIa-2 study results suggest a favourable immunological impact of influenza vaccination on the outcome of cancer patients receiving ICI immunotherapy, further encouraging the vaccine recommendation in this population and supporting translational investigations about the possible synergy between antiviral and antitumour immunity. Funding: The Federation of Italian Cooperative Oncology Groups (FICOG), Roche S.p.A., and Seqirus