Classical Hodgkin lymphoma (HL) is a rare hematological cancer, affecting preferentially young adults. Using a risk-adapted approach, HL has become highly curable (>80%) with front-line chemotherapy in addition with radiotherapy, despite long term significant toxicity. Some patients are primary refractory or relapse after first-line chemotherapy, requiring high dose chemotherapy with serious side effects. Studies of the microenvironment from HL tissue reveal ineffective inflammatory and immune cell infiltrate surrounding Reed-Sternberg cells, involving the Programmed cell Death 1 (PD-1)/PD-ligand-1 checkpoint pathways. Recently, immune checkpoint inhibitors demonstrated high efficacy for relapsed and refractory patients, with a favorable safety profile but indeterminate long term outcome. Guidelines for nivolumab or pembrolizumab treatment in HL remain to be established.

Recent advances in immuno-oncology with the development of anti-PD1/PD-L1 antibodies are revolutionizing oncological management. Immuno-oncology I currently developing in most histological types of cancer. However, the rate of success of anti-PD1/PD-L1 antibodies in monotherapy is limited by a limited to a subpopulation of patients accounting for about 25-30 % of patients in most indications. The development of new strategies is based on this observation with the aim to predict response or enhancing response rate. Thus, we note the development of different strategies aimed at better selecting patients or combining inhibitory checkpoints with other therapies in order to increase their effectiveness. This review will study therapeutic test strategies to validate these new associations.

Merkel Cell Carcinoma (MCC) is a rare neuroendocrine skin cancer that is associated with frequent recurrences and a high mortality rate. In the recent past years, incidence rates of MCC have increased in the USA, Australia and Europe. About one third of patients present metastatic disease at the time of diagnosis or will develop metastases in the course of their disease. Although advanced MCC is chemosensitive, responses to cytotoxic chemotherapy are mostly of short duration and toxicity is potentially high. Recently, considerable progress has been made in the MCC field with the arrival of immunotherapy, particularly anti-PD-1 and anti-PD-L1 antibodies which have demonstrated impressive frequency and durability of response and were well-tolerated. However, about 50 % of advanced patients do not respond to immunotherapy and urgent need exists to identify biomarkers and predictive factors. Moreover, many randomized prospective studies are evaluating the efficacy and safety of novel therapeutics and patients with advanced stages are encouraged to participate in clinical trials. This article synthetizes the actual clinical practice guidelines, the safety and efficacy data from the recent clinical trials and the on-going clinical trials to help clinicians in the treatment of MCC patients.

Drug-induced crystalline nephropathies are secondary to abnormal accumulation of crystals leading to parenchymal renal injuries. Methotrexate, used to treat a wide range of malignancies, is one of the various drugs accountable in this particular condition. We report a case of acute renal injury during the course of high-dose methotrexate therapy in a patient presenting primary cerebral diffuse large B-cell lymphoma. Interestingly, the kidney biopsy revealed intratubular methotrexate crystal formations. We also summarize the distinctive characteristics of main crystalline nephropathies in order to guide pathologists toward the many types of crystals encountered on renal biopsy.

Oral cancer drugs make the patient more active and autonomous. They reduce the number of hospital appointments and the risk of infection. However, they result in new problems such as the management of side effects. In this context, therapeutic education is essential. The first French therapeutic education programme for patients taking oral cancer drugs at home has been set up.

Until recently, advanced BCC were only accessible to a highly morbid surgery not necessarily proving to be carcinologic, and leaving terrible dysmorphic sequelae hard to accept by the patient. Another possibility, the only one in case of metastatic BCC, was chemotherapy which efficacy has never been proven in a clinical trial. Radiotherapy is most often not accessible because of previous radiotherapy or because of the localization or the extension of the lesion. The discovery of the importance of the sonic hedgehog pathway in the physiopathology of BCC has opened a new strategy with the development of targeted anti SMO drugs inactivating the pathway. Two molecules have become available following Phase I and II studies: vismodegib (Erivedge®) the first in class indicated for locally advanced and metastatic BCC and sonidegib (Odomzo®) indicated only for locally advanced BCC. The pharmacokinetic profiles of sonidegib and vismodegib showed several differences. No head to head comparative studies are available between these two drugs. Their pivotal phase II studies had similar study designs and endpoints. The objective response rate (ORR) by central review for vismodegib was 47.6% (95% CI 35.5-60.6) at 21 months follow-up. The ORR for sonidegib according to central review at 18 months follow-up is 56.1% (95% CI 43.3-68.3). Although both treatments share a similar adverse event profile with possible numerically differences in incidence, most patients will discontinue hedgehog inhibitors treatment in the long term because of side effects. Some resistant cases to these drugs have been described but are rather rare. In case of resistance or bad tolerability to the drug future hopes rely on immunotherapy currently under investigation. © 2018. Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Prise en charge des carcinomes basocellulaires difficiles à traiter réalisé avec le soutien institutionnel de Sun Pharma.

Physiological aging causes qualitative or quantitative immune system decline, also called immunosenescence. Older people with cancer are often ineligible for chemotherapy. The new immunotherapies (with PD1, PDL1 and CTLA4 checkpoint inhibitors) have proven their effectiveness in many tumor types regardless of age and are often better tolerated than chemotherapy. In the older population, the subgroup data from the different pivotal studies show fairly reassuring efficacy and safety data, despite the frequent lack of power given the small population included. There remains, however, some doubt that age may be a risk factor for hyperprogression. Studies focusing on older subjects and dedicated meta-analysis seem necessary to obtain more accurate data.

Intravitreal injections of medication are designed to obtain a high concentration in the posterior segment. We conducted a retrospective study of our practice of intravitreal injections to assess safety of the technique and short- and medium-term tolerability, and to analyze indications and the complications.

In 2013, the European Medicines Agency authorized a new pharmaceutical formulation of the trastuzumab for breast cancer treatment. The latter allows a sub-cutaneous injection that reduces significantly the injection time and permits an administration at home. This study aims to assess the experience of patients treated by trastuzumab subcutaneously at home in 2016, and the experience of the nurses who performed these injections. In 2017, a retrospective survey by phone calls could gather the impressions from 84 patients on their treatment. And 60 nurses answered to a written survey. The whole treatment session is estimated to last 30minutes to one hour by most of the patients (60%) and the nurses (85%), with an injection duration below 5 minutes (according to 71% of patients and 77% of nurses). The main side effects described were: rash (reported by 40% of patients and 52% of nurses) and pain (32% of patients and 68% of nurses). Among patients feeling pain, it was estimated as brief and weak by two thirds of them. Eighty-six per cent of patients found the session pleasant. The general impression of the nurses was also satisfying for almost all of them (89%). Overall, the feedback about subcutaneous injections of trastuzumab at home is very positive, for patients as for nurses. This new formulation improves quality and comfort in patients' care.

Daratumumab is a monoclonal antibody that targets CD38. It has an anti-tumor action on the myeloma cell and an immunomodulatory action. For relapsing and/or refractory myeloma patients, daratumumab is effective both alone and in combination and significantly improves progression-free survival. Daratumumab has been approved in 2016 in France for treatment of relapses or refractory multiple myeloma.

We report cases of delayed, sustained elevated intraocular pressure (IOP) associated with repeated intravitreal anti-VEGF injections (IVI), which ultimately resulted in the need for filtering surgery. Two of the three cases demonstrated severe IOP elevation despite maximal medical treatment following unilateral IVI and required urgent filtering surgery. Optic nerve involvement was severe in all three cases. These intravitreal injections were performed for exudative age-related macular degeneration (AMD), and the patients did not show any sign of glaucoma or ocular hypertension prior to the initiation of treatment. Elevated IOP secondary to intravitreal steroids is a well-known side effect, as is immediate transient IOP elevation associated with anti-VEGF injection. Late, sustained IOP elevation after repeated injections of anti-VEGF, described approximately ten years ago, is often underestimated. Its incidence is estimated between 2.1% and 13% according to studies and increases with the number of IVI (cumulative effect). The pathophysiologic process is becoming increasingly understood, and several risk factors for this chronic IOP elevation have been identified. Most often, it is a moderate IOP elevation for which topical monotherapy is sufficient, or sometimes two, three or four medications or even selective laser trabeculoplasty (SLT). However, filtering surgery may rarely be required. Our findings illustrate a little-described phenomenon: a sudden, severe, late IOP elevation in response to anti-VEGF by an "overflow" effect, requiring urgent filtering surgery.

Specific immune-related adverse events in lung cancer treatment are rare and it is important that they are identified as they may have important adverse consequences. We report such a case here.

The anti programmed death-1 (PD-1) and the programmed death ligand 1 (PD-L1) antibodies are used as immunotherapies in the treatment of many solid tumours. Cases of interstitial pneumonitis induced by anti PD-1 have been widely described, but there are fewer data with anti PD-L1. Avelumab is a new immunotherapy of the anti PD-L1 class.

Oral targeted therapies are a growing class of medication. After clinical trials conducted on a selected population, these molecules are usually approved at a fixed dose. However, oral tyrosine kinase inhibitors are characterized by a large intra and inter-individual pharmacokinetic variability, and a narrow therapeutic index. Hence, their prescription is hazardous and unsafe in non-selected people from daily clinical practice. The increasing number of available targeted therapies point out new challenges. These challenges should especially concern prescription for out of the ordinary patients, rules for dose adjustment according to factors of frailty. The ultimate goal is to ensure a safe and individualized prescription. Moreover, many of these molecules are metabolized by the CYP3A4, leading to a serious risk of drug interaction. These interactions might involve not only conventional medicine but also alternative and complementary medicines. These latter are more and more common but oncologists often lack experience about them. Finally, the oral route raises the issues of adherence, and the question of its assessment should now become a permanent part of patients care.

Chemotherapy-induced peripheral neuropathy (CIPN) is common with specific semiological characteristics. When CIPN appears, there are many difficulties in guaranteeing sustained treatment, especially with optimal protocol. Moreover, CIPN have bad repercussions on quality of life after cancer disease. In this article, we have achieved a current state of CIPN and try to report details about semiological characteristics and topography. We have also produced some epidemiological data. Nonetheless, we have not voluntarily introduced treatment because it will be the topic of further work.

Immune checkpoint inhibitors are becoming a standard treatment for many different cancers. Their toxicities are variable and include organ-specific dysimmune injuries and the development of systemic diseases.

Anti-tumoral immunotherapy is currently the basis of a profound modification of therapeutic concepts in oncology, in particular since the arrival of immune checkpoint inhibitors (ICI). In addition to their efficacy profile, these immune-targeted agents also generate adverse events. With the increasing use of ICI for a growing number of tumor types, awareness of immunotherapy-related adverse events is essential to ensure prompt diagnosis and effective management of these potentially serious adverse events.

The immunotherapies known as "inhibitors of checkpoint" (ICP) are monoclonal antibodies used since 2010 and have dramatically modified the management of the advanced or metastatic melanomas. By reactivating the anti-tumoral immune response, these antibodies can activate the immune system in all the tissues with a risk to induce immune related adverse events (IrAE). Thus, the adverse effect's profile of ICP is considered as very different from that usually associated with conventional chemotherapies. The objectives of our retrospective monocentric study were the evaluation of the real life's safety and efficiency of the ipilimumab and the pembrolizumab in patients with an advanced melanoma. Seventy-two patients treated by ipilimumab and\or pembrolizumab between August 1st, 2008 and December 31st, 2016 were investigated. The main IrAE occurring involved the gastro- intestinal, skin, and the endocrine systems. The average onset time of IrAE was 39, 104 and 68 days, respectively and their respective duration was of 67, 50 and 111 days. There were 13 events of grade III and IV along with one death. The overall survival was 5 months for the patients treated in monotherapy with ipilimumab, and 14 months for those treated by pembrolizumab. Our real life's study tends to confirm the current safety profile of ICP treatment. Moreover and according to our analyses, the drug sequence seems to have a global survival impact.

Immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1) have recently revolutionized anti-cancer therapy and are nowadays used in different metastatic cancers. These treatments may induce immune-related adverse events which frequently involve the digestive tract and, to a less extent the liver. The tissular injuries, which are still poorly characterized from a morphological and physiopathological point of view, may lead on one side to the interruption of a life-saving treatment and on the other side to the development of severe complications, if not death. Therefore, it is crucial to diagnose as early as possible and treat these digestive and hepatic adverse effects in an optimal way. This article aims to describe the clinical and pathological presentations of digestive and hepatic adverse events induced by these immunotherapies.