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Hodgkin lymphoma (HL) in older patients appears to be a different disease compared with younger patients with historically lower survival rates. This is related to a variety of factors, including increased treatment-related toxicity, the presence of comorbidities, and biologic differences. In order to better assess the clinical characteristics, treatment strategies, and outcome of this particular population, we conducted a population-based, retrospective analysis including 269 patients with HL older than 60 years (median age 71 years, range 60-94), treated between 2000 and 2017 in 15 referral centers across Switzerland. Primary endpoints were overall survival (OS), progression-free survival (PFS), and cause-specific survival (CSS). The vast majority of patients were treated with curative intent, either with a combined modality approach (chemotherapy followed by radiation therapy) or with systemic therapy. At a median follow-up of 6.6 years (95% confidence interval [CI], 6.0-7.6), 5-year PFS was 52.2% (95% CI, 46.0-59.2), 5-year OS was 62.5% (95% CI, 56.4-69.2), and 5-year CSS was 85.1.8% (95% CI, 80.3-90.1) for the entire cohort. A significant difference in terms of CSS was observed for patients older than 71 years in comparison to patients aged 60-70 years (hazard ratio 2.6, 1.3-5.0, p = 0.005). Bleomycin-induced lung toxicity (BLT) was documented in 26 patients (17.7%) out of the 147 patients exposed to this compound and was more frequent in patients older than 71 years (15/60, 25%). Outcome of HL pts older than 71 years appeared to decrease substantially in comparison to the younger counterpart. Treatment-related toxicities appeared to be relevant, in particular, BLT. New, potentially less toxic strategies need to be investigated in prospective clinical trials in this particular frail population.

Neoadjuvant, adjuvant and palliative systemic therapy of colorectal cancer Abstract. Neoadjuvant therapy is indicated for stage T3 / 4 and all N1 rectal cancers. Usually, chemoradiotherapy with capecitabine or 5FU is applied within a timeframe of 5 ½ weeks. 6 to 9 weeks later surgery is performed. The aim of neoadjuvant chemoradiotherapy is resectability and a low local recurrence rate. After surgery with curative intent, adjuvant chemotherapy increases the cure rate by 20 % in node-positive (stage III) colon cancer. For most patients, 3 months of capecitabine / oxaliplatin are adequate. For high risk patients, 6 months of therapy are necessary if a Folfox regimen is used. In the palliative setting, understanding the biology of the tumor is the key to systemic therapy. Next generation sequencing of tumor DNA is mandatory. Mismatch repair proficient tumors benefit from dual chemotherapy in combination with an antibody. Median survival increases from 6 to 30 months through palliative chemotherapy. Mismatch repair deficient tumors are in need of immunotherapy. Long lasting remission have been observed in this population.

Neoadjuvant, adjuvant and palliative systemic therapy of colorectal cancer

Standard conditioning regimens for autologous stem cell transplantation (ASCT) are often not tolerated by elderly patients, on one hand. Single high-dose melphalan, on the other hand, has been shown to be safe and active as a pretransplant preparative regimen in elderly patients. Y90 -Ibritumomab tiuxetan (Y90 -IT) is well tolerated and feasible in the transplantation setting. We therefore investigated the combination of high-dose melphalan and Y90 -IT as a conditioning regimen for patients ≥65 years of age. Patients with relapsed or resistant CD20-positive lymphoma in remission after salvage chemotherapy could be enrolled. High-dose therapy consisted of standard dose Y90 -IT (0.4-mCi/kg body weight) followed by melphalan at escalating doses (100, 140, 170 and 200 mg/m2 ) and ASCT. The primary objective was to identify the maximum tolerated dose; secondary end points were complete response (CR) rate 100 days after transplantation and toxicity. Twenty patients (median age 72 years) were included. No DLT occurred at any dose level. Thirteen patients completed the treatment, 11 were evaluable for response. Seven patients did not complete treatment because of mobilization failure (n = 3), progressive disease (n = 2), worsening of cardiac function (n = 1), and grade 3 dyspnea (n = 1). Seven patients achieved a CR/complete remission/unconfirmed (CRu) and 2 had stable disease. Five out of 7 responding patients were still alive more than 3 years after transplantation. The 2 patients with SD had a long-term survival of 3 and 5 years, respectively. Nonhematological grade 3 or higher treatment related adverse events (AEs) were infection (n = 6), including 2 cases of febrile neutropenia, diarrhea (n = 3), mucositis, anorexia, viral hepatitis, hypokalemia, dehydration, and multiorgan failure (n = 1 for each). The combination of Y90 -IT and high-dose melphalan is feasible before ASCT for elderly patients, with promising activity and manageable toxicity.

Standard conditioning regimens for autologous stem cell transplantation (ASCT) are often not tolerated by elderly patients, on one hand. Single high-dose melphalan, on the other hand, has been shown to be safe and active as a pretransplant preparative regimen in elderly patients. Y

Background Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have been recently approved for treatment of patients with metastatic melanoma and non-small cell lung cancer (NSCLC). Despite important clinical benefits, these therapies are associated with a diverse spectrum of immune-related adverse events (irAEs) that are typically transient, but occasionally severe or even fatal. Case presentation This autopsy case illustrates that clinically overt irAEs may represent only a fraction of the total spectrum of immune-related organ pathology in patients treated with immune checkpoint inhibitors. We report a comprehensive analysis of systemic irAE pathology based on the autopsy of a 35-year-old female patient with metastatic melanoma treated first with ipilimumab and then nivolumab. The clinical course was characterized by a mixed tumor response with regression of skin and lung metastases and fatal progression of metastatic disease in the small bowel, peritoneum and brain. During therapy with ipilimumab, radiographic features of immune-related pneumonitis were noted. The autopsy examination established a sarcoid-like granulomatous reaction of the lung, pulmonary fibrosis and diffuse alveolar damage. Importantly, a clinically unapparent but histologically striking systemic inflammation involving the heart, central nervous system, liver and bone marrow was identified. Severe immune-related end-organ damage due to lymphocytic myocarditis was found. Conclusions Autopsy studies are an important measure of quality control and may identify clinically unapparent irAEs in patients treated with immunotherapy. Pathologists and clinicians need to be aware of the broad spectrum of irAEs for timely management of treatment-related morbidity. Electronic supplementary material The online version of this article (doi:10.1186/s40425-016-0117-1) contains supplementary material, which is available to authorized users.

8560 Background: Standard conditioning regimens for ASCT are often not tolerated by elderly patients. Single agent high-dose melphalan has been shown to be safe and active in elderly patients with multiple myeloma. Y90-IT is a well-tolerated lymphoma treatment and feasible in the transplantation setting. We therefore investigated this combination of high-dose melphalan and Y90-IT as a conditioning regimen for elderly patients. Methods: Patients ≥65 years with relapsed or chemotherapy resistant CD20-positive lymphoma in PR or CR after salvage chemotherapy could be enrolled prior to stem cell mobilization. Myeloablation regimen consisted of standard dose Y90-IT followed by melphalan at escalating doses (100, 140, 170 and 200mg/m2, with a 3+3 phase I design) and by ASCT. The primary objective was to identify the MTD of melphalan in combination with standard dose Y90-IT (as defined < 1 DLT in 3 patients); secondary endpoints were toxicity and CR rate 100 days after transplantation. Results: Between 2006-2012 twenty patients were included. Median age was 72 years (range 66-77). One patient was considered retrospectively ineligible and was evaluable for toxicity but not for DLT. Thirteen patients received the treatment and were transplanted. Eleven patients were evaluable for DLT. No DLT occurred. Non-hematological grade 3 or higher treatment related adverse events were: infection (n=6, including 2 cases of febrile neutropenia), diarrhea (n=3), mucositis, anorexia, viral hepatitis, hypokalemia, dehydration and multi-organ failure (n=1). Seven patients did not start treatment because of mobilization failure (n=3), progressive disease (n=2), worsening of cardiac failure (n=1) and grade 3 dyspnea (n=1). Seven patients achieved a CR/CRu and 2 patients were stable 100 days after transplantation. Conclusions: The combination ofstandard dose Y90-IT and high dose melphalan (200mg/m2) is a safe and feasible conditioning regimen before ASCT for patients ≥65 years. The results show promising activity. Clinical trial information: NCT00392691.

The first administration of rituximab can cause important side effects due to cytokine release into the blood. It is therefore recommended to administer it over 4–6 hours. According to the manufacturer subsequent doses can be given in approximately 3 hours, but this is demanding for the patient (pt) and facilities and resources-consuming. A Canadian study has recently shown that rituximab can be given safely over 90 minutes from the second administration in combination with CHOP, provided that steroids and chemotherapy are administered before the antibody. We are conducting an infusion speed-escalation trial to verify if rituximab can be given in one hour without steroids pre-medication, in pts having received at least two previous doses of rituximab (with or without chemotherapy) in the previous 3 months. Further inclusion criteria include a normal cardiac function as evaluated by ECG and echocardiography. Cohorts of 3 patients are assigned to receive rituximab at a given initial infusion speed, to be increased by 100 mg /hour every 30 minutes. All receive standard anti-hystamine and paracetamol pre-medication. At every subsequent rituximab administration the initial speed is increased by 100 mg/h (intra-patient speed-escalation). If a pt experiences serious adverse events (SAE), then 6 pts are treated in the same cohort, in case of SAE in 2 of them the trial is discontinued. In each new cohort the initial speed is 100 mg/hr higher than in the previous cohort. Pts are monitored every 15 minutes for symptoms, blood pressure and hearth rate, hourly for temperature and an ECG is performed after treatment. For patients receiving chemo-immunotherapy, rituximab is given first and chemotherapy only later on the same day. Fifteen pts have so far been included (14 evaluable), with the first 4 cohorts complete. Median age was 60 (range 41–76), lymphoma type was diffuse large cell (8 pts), follicular (4 pts) and other indolent (3 pts). Two patients were treated with single agent rituximab and 12 in combination with chemotherapy. The median time from the last rituximab to inclusion in the study was 3 weeks (range 1–11). Overall, 3 cycles were given at a starting infusion speed of 200 mg/hr, 7 cycles at 300 mg/hr, 11 cycles at 400 mg/hr, 11 cycles at 500 mg/hr, 8 cycles at 600 mg/hr and 7 cycles at 700 mg/hr. The latter schedule allowed the administration of the whole prescribed drug in one hour. All pts tolerated the increased-speed infusion without major side effects. The blood pressure dropped by a median 10–15% of baseline, without symptoms and without significant differences between cohorts. The highest blood pressure drops were of respectively 25% and 29% without symptoms and spontaneously resolving within 15 minutes. There was no variation in the hearth frequency and no elevation of body temperature above 37°C. No relevant ECG changes were seen. We conclude that rituximab can be given in one hour without steroids pre-medication in pts who have already received at least two previous rituximab doses. The study is ongoing to evaluate the maximum infusion speed and will further explore if the latter is applicable from the second infusion on.