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Chimeric antigen receptor (CAR) T-cell therapy is currently approved for the treatment of B-cell non-Hodgkin lymphomas and B-cell acute lymphoblastic leukemia. Prolonged hematological toxicity is an emergent concern following CAR T cells and occurred in 30% of patients with unknown mechanism. Few cases of myelodysplastic syndrome (MDS) following CAR T-cell therapy were reported and attributed to previous chemotherapies in heavily pretreated patients. The authors report the case of a patient with diffuse large B-cell lymphoma treated with axicabtagene ciloleucel who developed prolonged hematological toxicity by day 28. During the follow-up, the diagnosis of MDS was made. The patient underwent allogenic hematological stem cell transplantation. The patient remains in complete remission of his lymphoma and MDS 19 months after hematological stem cell transplantation.

Praise be to Allah, Lord of the Worlds, and blessings and peace be upon our master Muhammad and his family and companions. And after : This study came under the title (The concept of contravention and its authority between Alhanafis and the public), to shed light on the most important area of disagreement between the Hanafis and the public and to extract the fruit of the disagreement through jurisprudential applications. I concluded that fundamentalists consider the concept of contravention as a justification which should be considered in scientific authorship , people's contracts, their anecdotal actions and all their dealings; because the people's convention and idioms in this issue in expressing their intentions indicates that, otherwise it would be in vain to introduce the restriction in their custom, However, the disagreement occurred in invoking the concept of contravention in the texts of the Sharia to the first two sayings that the concept of contravention is not an argument in the texts of Sharia, to which the Hanafis went to those who agreed with them, and the second: the concept of the makhala is a legitimate argument except the concept of the title, and to it went the majority of the fundamentalists from the Maliki and Shafi’i and the Hanbalis, but the public restricted their authority to eight conditions.

Background Recent meta-analysis showed that immune checkpoint inhibitors (ICIs) have comparable activity between younger and older patients. However, little is known about efficacy and safety of ICI in elderly patients with relapsed/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). The aim of this study is to compare the efficacy of ICI for patients aged ≥70 y to that for younger patients, while taking into account potential confounding factors. Methods A retrospective study was conducted at four hospitals in France. Patients treated with ICI for R/M SCCHN between September 2014 and December 2018 were eligible. Patients’ charts were reviewed for clinical and radiological data as well as oncologic outcomes. Results We included 226 patients, of whom 67 were aged ≥70 years. Objective response rate (ORR), median overall survival (OS) and median progression-free survival (PFS) were 23%, 9.7 months and 2.7 months, respectively, for elderly patients, compared to 13%, 8.7 months and 1.9 months for younger patients (respective p-values: 0.071, 0.87 and 0.21). After adjustment for performance status, site of progression, number of ICI drugs, time between initial diagnosis and ICI start and number of previous lines, age ≥70 years was significantly associated with a better PFS (hazard ratio [HR], 0.66; p = 0.021) but not OS (HR, 0.91; p = 0.59). Grade 3-5 adverse events (AEs) occurred in 15% of patients aged ≥70 years and in 8% of younger patients (p = 0.13). Conclusion Patients aged ≥70 years with R/M SCCHN may respond to ICI similarly as younger patients in terms of ORR, OS and PFS, while maintaining comparable rate of AEs.

Advances in molecular profiling of newly diagnosed diffuse large cell B lymphoma (DLBCL) have recently refine genetic subgroups. Genetic subgroups remain undetermined at the time of relapse or refractory (RR) disease. This study aims to decipher genetic subgroups and search for prognostic molecular biomarkers in patients with RR-DLBCL. From 2015 to 2021, targeted next-generation sequencing analyses of germline-matched tumor samples and fresh tissue from RR-DLBCL patients were performed. Unsupervised clustering of somatic mutations was performed and correlations with patient outcome were sought. 120 patients with RR-DLBCL were included in LNH-EP1 study and a molecular tumor landscape was successfully analyzed in 87% of patients (104/120 tumor samples). The median age was 67.5 years (range 27.4-87.4), median number of previous treatments was 2 (range 1-9). The most frequently mutated genes were TP53 (n=53 mutations; 42% of samples), CREBBP (n=39; 32%), BCL2 (n=86; 31%), KMT2D (n=39; 28%) and PIM1 (n=54; 22%). Unsupervised clustering separated three genetic subgroups entitled BST (enriched in BCL2, SOCS1 and TNFRSF14 mutations); TKS (enriched in TP53, KMT2D and STAT6 mutations); and PCM (enriched in PIM1, CD79B and MYD88 mutations). Median overall survival was 11.0 (95%CI: 8.1-12.6) months. Overall survival was not significantly different between the three genetic subgroups. GNA13 mutant was significantly associated with an increased risk of death (HR: 6.6 [95%CI: 2.1-20.6]; p=0.0011) and shorter overall survival (p=0.0340). At the time of relapse or refractory disease, three genetic subgroups of DLBCL patients were delineated, which could help advance precision molecular medicine programs. This article is protected by copyright. All rights reserved.

Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of rare hematologic malignancies accounting for less than 10% of non-Hodgkin lymphomas. The 2016 classification of World Health Organization recognized 29 different entities of PTCLs. These subgroups are characterized by different molecular and genetic patterns. For nearly 30 years, little improvement in the treatment of PTCLs has been noticed due to the paucity of randomized trials and anthracycline-based chemotherapy remains the mainstay of first-line treatment. In front-line setting, ECHELON-2, the first randomized controlled Phase III clinical trial, recently met its primary endpoint of PFS demonstrating the superiority of BV containing regimen when compared to standard CHOP in patients with CD30 positive PTCLs. The role of therapeutic intensifications such as autologous or allogenic stem cell transplantations remains controversial in first-line setting and in relapsed/refractory disease due to the lack of studies clearly addressing this question and the recently published negative studies. PTCLs are often refractory to first-line chemotherapy and tend to relapse after an initial response. New agents have been approved for relapsed/refractory disease such as Histone deacetylase inhibitors, folate analogue metabolic inhibitor or CD30 antibody drug conjugated. Despite an acceptable response to these agents, progression-free survival remains very poor. New strategies such as combinations of different agents have been evaluated in order to improve outcomes. Innovative drugs in the fields of epigenetics, immunomodulation within the tumor microenvironment, and direct targeting of tumor cells to CD30 and T-cell receptor abnormalities open new perspectives to improve the treatment of PTCLs.

International audience; Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) characterized by the translocation t(11;14) (q13;q32) and a poor response to rituximab–anthracycline-based chemotherapy. High-dose cytarabine-based regimens offer a durable response, but an important number of MCL patients are not eligible for intensive treatment and are ideal candidates for novel targeted therapies (such as BTK, proteasome or BCL2 inhibitors, Immunomodulatory Drugs (IMiDs), bispecific antibodies, or CAR-T cell therapy). On the bench side, several studies aiming to integrate the tumor within its ecosystem highlighted a critical role of the tumor microenvironment (TME) in the expansion and resistance of MCL. This led to important insights into the role of the TME in the management of MCL, including potential targets and biomarkers. Indeed, targeted agents often have a combined mechanism of action on the tumor B cell but also on the tumor microenvironment. The aim of this review is to briefly describe the current knowledge on the biology of the TME in MCL and expose the results of the different therapeutic strategies integrating the TME in this disease.

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the monoclonal proliferation of immature progenitors. It is the most common acute leukemia in adults and its incidence increases with age. The standard traditional treatment in fit patients was the ‘3 + 7’ regimen and cytarabine consolidation followed or not with allogeneic stem cell transplantation. Recently, several targeted therapies such as gemtuzumab ozogamicin targeting the CD33+ AML, midostaurin, gilteritinib and crenolanib inhibiting FLT3-positive AML and ivosidenib and enasidenib blocking IDH-mutated AML have been approved. These new drugs led to the change of the landscape of the treatment of AML and transforming this disease to a targetable one. We aimed in this paper to review the implications of each new target, the mechanisms of action of these new drugs and we discuss all the studies leading to the approval of these new drugs in their indications according to each target.

Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) is the most common subtype of B-ALL in adults and its incidence increases with age. It is characterized by the presence of BCR-ABL oncoprotein that plays a central role in the leukemogenesis of Ph+ ALL. Ph+ ALL patients traditionally had dismal prognosis and long-term survivors were only observed among patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1). However, feasibility of allo-HSCT is limited in this elderly population. Fortunately, development of increasingly powerful tyrosine kinase inhibitors (TKIs) from the beginning of the 2000′s dramatically improved the prognosis of Ph+ ALL patients with complete response rates above 90%, deep molecular responses and prolonged survival, altogether with good tolerance. TKIs became the keystone of Ph+ ALL management and their great efficacy led to develop reduced-intensity chemotherapy backbones. Subsequent introduction of blinatumomab allowed going further with development of chemo free strategies. This review will focus on these amazing recent advances as well as novel therapeutic strategies in adult Ph+ ALL.

Bladder cancer is the seventh most frequent cancer worldwide. The majority of patients present with nonmuscle invasive disease, while 20% of the patients are diagnosed with muscle-invasive bladder cancer. The treatment of nonmuscle invasive disease is endoscopic resection followed by intravesical adjuvant treatment for high risk patients. The standard treatment of localized muscle-invasive disease is neoadjuvant chemotherapy followed by radical cystectomy. Platinum-based chemotherapy is the first-line treatment in locally advanced or metastatic urothelial carcinoma. Immune checkpoint inhibitors have been approved for the treatment of metastatic urothelial carcinoma as second-line treatment or first-line in platinum-ineligible patients. Recently, pembrolizumab have been approved in bacillus Calmette-Guérin (BCG)-refractory nonmuscle invasive bladder cancer. This review summarizes the current evidence concerning immunotherapy in the treatment of urothelial carcinoma.Lay abstract Bladder cancer is one of the most frequent cancers worldwide with multiple known risk factors such as cigarette smoking and occupational exposures. The majority of patients present with a superficial disease treated with endoscopic resection and intravesical treatment if needed. The localized form of bladder cancer is treated with chemotherapy followed by radical cystectomy. Metastatic bladder cancer is an incurable disease and historic treatment remains on chemotherapy. Recently, immunotherapy has been approved for the treatment of bladder cancer after progression on chemotherapy. In this article we reviewed the most recent available data concerning immunotherapy for the treatment of early-stage and advanced disease.

Background High Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC). Methods The National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers. Results Of 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m2 (range 12.1–66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2–48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02–1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect. Conclusion Overweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor., Highlights • This is the first large multicenter cohort reporting BMI’s effect on outcomes among patients with metastatic breast cancer. • Overweight or obese status does not negatively influence outcome of metastatic breast cancer patients, whatever the subtype. • Underweight is a strong negative independent prognostic factor on outcomes, whatever the subtype.

6036 Background: Salvage chemotherapy after progression on immune checkpoint inhibitors (ICIs) was associated with an objective response rate (ORR) of 30% in patients (pts) with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We aimed to investigate the efficacy of taxanes + cetuximab (TC) +/- platinum chemotherapy in pts with R/M SCCHN who failed ICIs in palliative setting. Methods: A retrospective study was conducted at 7 French university hospitals. Eligibility criteria were pts treated with ICI for R/M SCCHN, who progressed after treatment with ICI and received TC +/- platinum salvage chemotherapy between August 2017 and December 2021. Clinical and radiological data and outcome were collected from review of medical records. Results: Ninety-nine pts met eligibility criteria: 63 pts received TC and 36 pts received triplet regimen (TR). The median age was 61 years (range 24-78) and 79% of pts were male. Forty-two pts (42%) had platinum-refractory disease (PRD) after multimodal treatment, 13 pts received prior taxanes and 24 pts received prior cetuximab. The median PS at salvage chemotherapy was 1 (range 0-3). ICIs were given as first-line treatment in 70% of pts including those with PRD. The ORR of the entire cohort was 62% (61/99) including 5 complete responses (CR) and the disease control rate was 79% (78/99). The median progression-free survival of the entire cohort was 4.4 months and the median overall survival (OS) was 7.5 months. The 5 pts who had CR as best response are still in remission after a median follow-up of 24 months (range 8-58). The ORR of TC subgroup was 57% (36/63) and the ORR of TR subgroup was 69% (25/36). Furthermore, the ORR in the PRD subgroup of pts was 54% (39/72), and the ORR in the subgroup of pts who were not chemo naïve was 54% (39/72). The ORR in pts who previously received cetuximab was 50% (12/24) vs 75% (49/75) in those who did not. The ORR in pts who previsouly received taxanes was 38% (5/13) vs 65% in those who did not. Finally, the ORR in PRD pts and treated with TR was 50% (7/14) and the ORR in pts who previously received platinum-based treatment or PRD and treated with TR was 55% (11/20). Conclusions: TC +/- platinum chemotherapy was highly effective in pts R/M SCCHN who progressed on ICIs with an ORR of 62% and DCR of 79%. Further investigations are warranted.

Burkitt’s lymphoma and its leukemic form (Burkitt cell acute lymphoblastic leukemia) are a highly aggressive disease. We review the classification, clinical presentation, histology, cytogenetics, and the treatment of the disease. Burkitt’s lymphoma might be associated with tumor lysis syndrome which is a potentially fatal complication that occurs spontaneously or upon initiation of chemotherapy. Major improvements were made in the treatment of pediatric and adults population using short-course dose-intensive chemotherapy regimens, usually 1 week after a prephase induction. Addition of Rituximab to chemotherapy has become a standard of care. Relapsed/refractory disease has a very poor prognosis and the benefit from autologous/allogeneic hematopoietic stem cell transplant remains uncertain. Rituximab-based short-course dose-intensive chemotherapy is the standard of care of Burkitt’s lymphoma even in the immunodeficiency-related form.

Introduction: Brain metastases (BM) are rare in colorectal cancer (CRC) and are associated with a dismal prognosis. This work aims to report the rate of BM in CRC patients treated in a single institution, along with survival and prognostic factors. Methods: Medical charts for patients with histologically proven CRC were retrospectively reviewed. Results: A total of 538 patients were identified, of whom 33% developed any metastatic disease and 4.4% presented BM. Lung was the most frequently associated metastatic site (in 68% of the cases). The only factor independently associated with BM development was the presence of metastatic disease at the time of initial presentation. The median duration from initial diagnosis to BM development was 38.6 months (SD 29.1 months). Median survival after BM development was 62 days (95% confidence interval [CI] 56–68). Patients diagnosed with BM within 1 year of cancer diagnosis responded significantly better to treatment than those who acquired BM later, with a median survival after BM diagnosis of 261 days versus 61 days, respectively ( p = .002). Patients with BM who received antiangiogenic therapy had an improved median survival compared to those who did not (151 days vs 59 days, p = 0.02; hazard ratio for death 0.29 [95% CI 0.09–0.94]). Conclusion: CRC with BM is an aggressive disease resistant to standard treatment and is associated with poor outcomes. Adding antiangiogenic therapy might be of value for those patients. Patients with BM developing early in the disease course might respond better to treatment.

Head and neck squamous cell carcinoma (HNSCC), a heterogeneous group of upper aerodigestive tract malignancies, is the seventh most common cancer worldwide. Tobacco use and alcohol consumption were the most identified risk factors of HNSCC. However, human papilloma virus, a sexually transmitted infection, has been determined as another primary cause of HNSCC. Early-stage disease is treated with surgery or radiotherapy. Recurrent or metastatic HNSCC is associated with poor prognosis with a median overall survival of 10 months. The EXTREME protocol is commonly used in first-line setting. Recently, pembrolizumab, an anti-programmed death-1 agent, has been approved by the US Food and Drug Administration for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy. It demonstrated a durable objective response rate with a good safety profile and quality of life. Many ongoing trials are evaluating the use of pembrolizumab for the treatment of HNSCC in various indications such as adjuvant and neoadjuvant setting, maintenance and recurrent disease, alone or in combination with chemotherapy, radiation and targeted therapy. Finding those biomarkers predictive of response to immune checkpoints inhibitors has been a major concern. However, markers have been identified, such as PD-L1 expression, human papilloma virus infection, interferon-γ signature score, microsatellite instability and neoantigen production.

TEZ11685 Tez (Doktora) -- Çukurova Üniversitesi, Adana, 2019. Kaynakça (s. 121-130) var. iii, 131 s. : res. (bzs. rnk.), tablo ; 29 cm. Bu çalışmada Mersin Körfezi’nden izole edilen Pseudomonas ve Aeromonas bakterilerinin antibiyotik ve ağır metal dirençlilik düzeyleri belirlenmiş. Tetrasiklin antibiyotiğine dirençli bakterilerinde dirençlilik mekanizması tanımlanmıştır. Dört mevsimde çalışma boyunca toplamda 340 bakteri izole edilmiştir. Bu izolatların 94 tanesi Aeromonas türü, 186 tanesi Pseudomonas türü bakteri olarak tanımlanmıştır. Antibiyotik test sonuçlarına göre, Pseudomonas spp. ve Aeromonas spp. için en yüksek antibiyotik dirençliliği Tetrasiklin ve Kanamisin antibiyotiklerine karşı sırasıyla% 76.9 ve% 91.3 olarak tespit edilmiştir. Pseudomonas spp. ve Aeromonas spp. bakterilerinin Kadmiyum, Kurşun, Bakır ve Nikel ağır metallerine karşı dirençlilik düzeyleri belirlenmiş. Esherichia coli K-12 bakterisi referans suş olarak kullanılmıştır. Ağır metal test sonuçlarına göre Pseudomonas spp. bakterileri Kadmiyum’a %71.5, Nikel’e %69.35, Bakır’a %67.2 ve Kurşun’a %23.65’i direçli olarak belirlenmiştir. Aeromonas spp. bakterileri Kadmiyum ve Nikel’e %79.78’i, Bakır’a %78.72’si, Kurşun’a ise %19.14’ü dirençli olarak belirlenmiştir. Tetrasikline karşı dirençli Pseudomonas spp. bakterilerinden 17, Aeromonas spp. bakterilerinden 13 tane rastgele seçilen izolatlarda Tet A, B, C, D, E, M, W ve X gen kasetleri taraması yapılmıştır. Tet A, B, C, D, E, M, W ve X gen kasetleri taraması sonucunda sırası ile 16, 13, 14, 14, 11, 7, 11 ve 5 Pseudomonas spp. bakterisi ve yine sırası ile 11, 9, 9, 10, 7, 7, 8 ve 5 Aeromonas spp. bakterisi pozitif olarak tespit edilmiştir. In this study, antibiotic and heavy metal resistance were determined of Pseudomonas and Aeromonas bacteria isolated from the Bay of Mersin. The resistance mechanism of tetracycline antibiotic resistant bacteria has been described. In four seasons, 340 bacteria were isolated. These isolated bacteria were identified as 94 Aeromonas species and 186 Pseudomonas species. According to antibiotic test results, the highest antibiotic resistance was determined to Tetracycline and Kanamycin antibiotics as 76.9% and 91.3% for Pseudomonas and Aeromonas, respectively. The heavy metal resistance levels of Pseudomonas and Aeromonas bacteria to Cadmium, Lead, Copper and Nickel were determined and Esherichia coli K-12 bacteria was used as reference strain. According to heavy metal test results, Pseudomonas bacteria were determined as rezistance as 71.5% to Cadmium, 69.35% to Nickel, 67.2% to Copper and 23.65% to Lead. The Aeromonas bacteria were determined as rezistance as 79.78% to Cadmium and Nickel, 78.72% to Copper and 19.14% to Lead. Thirteen of Pseudomonas bacteria and 13 from Aeromonas bacteria which was randomly selected resistant to Tetracycline antibiotic. In these bacteria, Tet A, B, C, D, E, M, W and X gene cassettes were screened. According to gene cassettes screening of Tet A, B, C, D, E, M, W and X were positive as 6, 13, 14, 14, 11, 7, 11 and 5 for Pseudomonas bacteria and 11, 9, 9, 10, 7, 7, 8 and 5 for Aeromonas bacteria were determined as positive, respectively. Bu çalışma Ç.Ü. Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir. Proje No: FDK-2016-5796.

Background LIPI, based on derived NLR (neutrophils/(leucocytes-neutrophils)) and lactate dehydrogenase (LDH) level, has been correlated to ICI outcomes in advanced non small cell lung cancer. We evaluated if HN-LIPI could offer the same role in R/M SCCHN. Methods This is a multicentric (9 European centers) retrospective study including R/M SCCHN patients (pts) treated with ICI from September 2014 to May 2019 and a control cohort (N = 83) only treated with chemotherapy. Baseline biological and clinicaldata were collected from medical records. According to dNLR>3 and LDH > upper limit of normal, HN-LIPI defines 3 groups (Good: 0 factor; Intermediate: 1 factor; Poor: 2 factors).The primary endpoint was overall survival (OS), and secondary endpoints was progression free survival (PFS). Results We included 273 pts (84% male, 84% smokers and 87% with PS ≤ 1, median age 59 years). Primary tumor locations were: oropharynx (37%), oral cavity (23%) and hypopharynx (17%). p16by immunohistochemistry was positive in 33% oropharynx pts. ICI were administered in 53% of patients as monotherapy and in 47% in combination. The median number of prior lines was 2 (1-7) with 65% of pts receiving ≥2. Median follow up of 13.2 months (mo).The median (m) PFS and OS were 2.84 mo [2.53-3.52] and 11.8mo [9.4-15.8]. dNLR >3 was associated to poor OS(HR 1.6, 95%CI: 1.1-2.3) but not with PFS (p = 0.11). LDH was not associated with endpoints. Median OS for good, intermediate and poor LIPI groups were: 15.9mo, 8.9mo and 6.2mo, respectively (p=.03). In univariate analysis, Intermediate and Poor risk groups were associated with OS (HR:1.5 95%CI:1.1-2.2 and HR:2 95%CI:1.0-4. respectively ). There was trend to better objective response rate in the good risk group compared with intermediate and poor (36%, 22% and 18%, p = 0.09). Conclusions Baseline HN-LIPI is associated with worse OS for ICI in R/M SCCHN but not with PFS. Control cohort results and multivariate models will be further presented at the congress, which would elucidate the prognostic and/or predictive impact in R/M SCCHN population. Legal entity responsible for the study Neus Baste. Funding Has not received any funding. Disclosure V. Cristina: Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: Ely Lilly; Advisory / Consultancy: Servier; Advisory / Consultancy: Celgene; Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: Merck-Serono. A. Garcia Castano: Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Pierre Fabre; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Pierre Fabre. R. Mesia Nin: Advisory / Consultancy: Merck; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Nanobiotix; Speaker Bureau / Expert testimony: Merck; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: MSD. M. Taberna: Non-remunerated activity/ies: Merck Serono; Non-remunerated activity/ies: AstraZeneca; Travel / Accommodation / Expenses: Merck Serono; Travel / Accommodation / Expenses: Nanobiotics; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Bristol-Myers. B. Besse: Travel / Accommodation / Expenses: AbbVie; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Biogen; Travel / Accommodation / Expenses: Blueprint Medicine; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: Eli Lilly; Travel / Accommodation / Expenses: GSK; Travel / Accommodation / Expenses: Ignyta; Travel / Accommodation / Expenses: IPSEN; Travel / Accommodation / Expenses: MERCK; Travel / Accommodation / Expenses: KGaA; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Nektar; Travel / Accommodation / Expenses: Onxeo; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Pharma Mar; Travel / Accommodation / Expenses: SANOFI; Travel / Accommodation / Expenses: Spectrum pharmaceuticals; Travel / Accommodation / Expenses: Tiziana Pharma; Travel / Accommodation / Expenses: Takeda. N. Baste-Rotllan: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Nanobiotics; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: MSD. All other authors have declared no conflicts of interest.