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Background Coronavirus disease 2019 (COVID-19) has affected more than 210 million people worldwide. An optimal therapeutic approach for COVID-19 remains uncertain, to date. Since the history of cancer was linked to higher mortality rates due to COVID-19, the establishment of a safe and effective vaccine coverage is crucial in these patients. However, patients with cancer were mostly excluded from vaccine candidates’ clinical trials. This systematic review aims to investigate the current available evidence about the immunogenicity of COVID-19 vaccines in patients with cancer (PsC). Patients and methods All prospective studies that evaluated safety and efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included, with immunogenicity after the first and the second dose as the primary endpoint, when available. Results Vaccination against COVID-19 for PsC seems overall safe and immunogenic after well-conducted vaccinations schedules. Yet, the seroconversion rate remains lower, lagged or both compared to the general population. Patients with hematologic malignancies, especially those receiving B cell depleting agents in the last 12 months are the most at risk of poor seroconversion. Conclusion A tailored approach to vaccination may be proposed to PsC, especially on the basis of the type of malignancy and of the specific oncologic treatments received.

Objectives To evaluate the efficacy and tolerability of an attenuated immunochemotherapy regimen based on cytarabine, etoposide and dexamethasone plus rituximab (R-mini-CYVE) in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Methods We included pretreated adult patients with B-cell NHL who were ineligible for high-dose immunochemotherapy (HDT). Cytarabine and etoposide were given at four different dose levels, depending on the patient's frailty. Up to 8 cycles were administered. Results Between 2013 and 2019, 56 patients with diffuse large B-cell lymphoma (n = 45, 80%) and indolent B-cell lymphoma (n = 11, 20%) were included. Median age was 75 (range: 36-88). Nineteen patients (35%) had a performance status ≥2. Patients received a median of 4 cycles of R-mini-CYVE. The objective response and the complete response rates were 50% and 33%, respectively. Median progression-free survival and overall survival times were 5.7 (95% CI: 0.5-10.9) and 14.7 (95% CI: 3.5-25.9) months, respectively. Grade ≥3 anaemia, thrombocytopenia and neutropenia occurred in 44%, 55% and 60% of the patients, respectively. The most frequent non-haematological grade ≥3 adverse events were sepsis (21%), fatigue (13%) and cytarabine-related neurotoxicity (5%). Conclusion R-mini-CYVE demonstrated a meaningful antitumour efficacy and an acceptable safety profile in patients with relapsed/refractory B-cell NHL who were ineligible for HDT.

Background Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy (CT) are the current standard of therapy in several cancer types. Patients (pts) with lung cancer display higher response rates to CT when given after ICIs. Although ICIs have failed to demonstrate antitumour activity in microsatellite stable (MSS) metastatic colorectal cancer (mCRC), little is known about CT effect after ICIs. We aimed to assess whether sequential ICIs followed by CT may be an alternative therapeutic approach in a population of pts with mCRC. Material and methods We retrospectively assessed CT after ICI (CAICI) failure in pts with mCRC. The ICI regimen consisted of anti-PD(L)1 alone or in combination. The primary end-point was objective response rate. Progression-free survival (PFS) and overall survival (OS) were secondary end-points. Results Between 2014 and 2018, 29 pts with mCRC received CAICI (MSS tumours, 27 pts [86%]). The median number of previous lines was 4 (range, 2–7). Regimens included TAS-102 (n = 14), FOLFIRI (irinotecan, leucovorin, and fluorouracil; n = 6) or FOLFOX (oxaliplatin, leucovorin, and fluorouracil; n = 4), regorafenib (n = 3) and carboplatin (1 pt with BRCA mutation). Partial response and stable disease were observed in 4 (19%) and 9 (43%) pts, respectively (disease control rate, 62%). The median PFS and OS were 3.8 months (95% confidence interval [CI] = 1.5–5.4) and 8.0 months (95% CI = 4.2–14.0), respectively. Conclusion ICIs administered before CT might enhance cytotoxic effects even in pts with immunorefractory MSS mCRC. The results of this small cohort need to be validated in independent prospective cohorts. The role of ICIs as modifiers of both tumour cells and microenvironment in mCRC deserves further research.

Background: The COVID-19 pandemic deeply threatens the rigorous conduct of clinical trials, notably by delaying site initiation visits, patient enrolment, treatment administration, trial-associated procedures, and data monitoring. Unlike most other medical specialties, clinical trials are an integral part of patient care in oncology. Limiting access to clinical trials therefore results in a loss of chance for patients. Methods: In this retrospective single-center study, we collected clinical trial-specific items (including patient-related or trial management-related items) during the first pandemic wave (March– June 2020) and lockdown (March 17th-May 11th) at Gustave Roussy, and compared them to those of the same period in 2019. Results: In March 2020, 84 phase I (P1) and 210 phase II/III (P2/3) trials were open. During the first pandemic wave, 21 (25%) P1 and 20 (9%) P2/3 trials were temporarily halted, following a unilateral sponsor decision in virtually all cases;all but one were industry-sponsored. Despite this, all important metrics of the P1/2 trial activity remained similar to those of 2019, including the number of patients referred for inclusion (599 vs 620), inclusion consultations (215 vs 247), patients starting treatment (130 vs 130), Internal Review Board (IRB) submissions (14 vs 16), and site initiation visits (11 vs 15), all in 2020 vs 2019, respectively. The impact of the first lock-down was more marked on P2/3, with 152 patient inclusions (vs 346 in 2019), 125 randomizations (vs 278), 43 IRB submissions (vs 50) and 34 site initiation visits (vs 40). However, in parallel, 475 patients were included in three “COVID and cancer” trials. Among the 443 P1 and 2851 P2/3 patients, 198 and 628 COVID-19 PCR were performed internally, and five and 15 (2.5%) were positive, respectively. One patient with a community-based COVID-19 died after transfer in intensive care. Conclusions: Cancer clinical trials can, and must be maintained despite challenges brought by COVID-19. Sharing experiences and retrospectively evaluating the impact on patients’ safety and cancer-related outcomes will be critical to durably improve the clinical trials conduct and to anticipate at best challenges brought by future similar crises. Legal entity responsible for the study: Gustave Roussy. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Background: Outcomes and risk factors associated with COVID-19 worsening among cancer patients have previously been reported. However, the actual impact of SARs-Co-V2 infection on the cancer treatment strategy remains unknown. Here, we report the Gustave Roussy (GR) experience, one year after the onset of the pandemic focusing on the impact of COVID-19 in patients with ongoing management of oncohematological disease. Methods: All patients positively tested for SARS-CoV-2 and managed at GR between Mar 14th 2020 and Feb 15th 2021 (data cut-off) have been included. Patients underlying oncohematological disease and COVID19 characteristics have been collected. Cancer and COVID-19 management and outcomes have been assessed. Primary endpoint was the overall impact of COVID-19 on oncological and hematological treatment strategy assessed at 1, 3, 6 and 12 months. Results: At the time of the analysis, 423 patients (median age: 62 years) were found positive for SARS-CoV-2 and managed at GR with a median follow up of 5.6 months (0-13 months). Among them, 284 (67%) were admitted due to COVID-19. Clinical deterioration occurred in 87 patients (21%), 43 patients (10%) were transferred in intensive care unit and 123 (29%) patients died, among which 47 (11%) died from COVID-19. Overall, 329 (78%) patients were on active treatment for underlying oncohematological disease at time of COVID diagnosis. Impact of COVID-19 on cancer treatment strategy in those patients is presented in the Table. The majority (N=268, 81%) had no change in oncological strategy. For those who experienced a delay, median delay in treatment was 21 days (N=99, [1-77]), 30 days (N=15, [15-56]), 7 days (N=8,[3-35]) for systemic treatment, surgery and radiotherapy respectively. [Formula presented] Conclusions: COVID-19 outbreak is associated with a significant mortality in patients with cancer. However, for patients who did not die from COVID-19, we provide the first report supporting that ongoing treatment was maintained or could be resumed in the majority of cases in a timely manner. Legal entity responsible for the study: Gustave Roussy. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Background: The severe pneumonitis in coronavirus disease 2019 (COVID-19) requires prolonged treatment in intensive care units, leading to overwhelmed hospital facilities Treatment with tocilizumab (Actemra, Roche), a monoclonal antibody targeting interleukin 6 receptor (IL6R), has shown promising efficacy in alleviating the severe pneumonitis However, only around 50% of the treated patients benefit from this intervention It is therefore an unmet medical need to identify biomarkers associated with the severity of disease and theranostic biomarkers to predict and differentiate potential responders from non-responders to the treatment Methods: An unbiased hyper reaction monitoring mass spectrometry (HRM™-MS) approach was used to analyze serum samples from severe COVID-19 cases before and 7 days after treatment with tocilizumab (n = 28), enabling simultaneous identification and quantification of all detectable serum proteins All samples were measured using 1h gradient on a nano-flow LC-MS/MS setup operated in data-independent acquisition (DIA) mode Data was extracted using Spectronaut™ (Biognosys) Univariate and multivariate statistical analyses were conducted to identify biomarker candidates Pathway analysis was used to identify dysregulated biological functions and signaling pathways Results: Over 450 proteins were quantified across all samples by HRM-MS Univariate statistical analysis identified significantly changing proteins across conditions (mortality day 30, pre-post treatment, responder/non-responder, q-value > 0 05 and fold change >1 5) Multivariate analysis (PLS-DA) was also used to classify proteins based on their abundance across condition Proteomic data was further integrated with clinical outcome data to identify a panel of protein biomarker candidates potentially useful in predicting tocilizumab treatment efficiency and the COVID-19 disease severity Conclusions: Unbiased proteomic profiling of COVID-19 patient serum identified a panel of candidate protein biomarkers that associate with tocilizumab treatment response as well as the ensuing course of the disease Further validation of these biomarker candidates opens the way for a personalized medicine approach in treating COVID-19 Legal entity responsible for the study: Biognosys AG Funding: Biognosys AG Disclosure: J-M Michot;F-X Danlos;F Pommeret;A Marabelle: Full/Part-time employment: Institut Gustave Roussy V Dozio;E Kishazi;C Escher;K Kakalacheva - Beeler: Full/Part-time employment: Biognosys AG M Vasse;J Rohmere;M Roumier: Full/Part-time employment: Hopital Foch

Background Patients (pts) living with cancer are exposed to higher risk for thrombotic event (TE). The thrombotic risk (TR) is related to cancer disease and could also be associated with anti-cancer drugs such as antiangiogenic (AA). AA are currently being used more and more widely, alone or in combination (combo) with anti-PD(L)1 immunotherapies. It isn’t known whether combining anti-PD1 or PD-L1 with AA drug could increase the risk of TE. This study aimed at evaluating the TR in patients receiving a combo of AA and anti-PD1 or PD-L1. Methods Observational study conducted from January 2017 to September 2019 and retrospectively investigated all consecutive adults pts with cancer treated with a combo of AA plus anti-PD(L)1. All TE (venous and arterial) occurring following investigated treatment(s) and Khorana scores (KS) were analyzed. The TR was assessed in pts receiving the combo and compared with pts treated with single anti-PD(L)1. For the single anti-PD(L)1 cohort, data were collected from the pharmacovigilance Register of Severe Adverse Effects of Immunomodulatory Monoclonal Antibody in Cancer (REISAMIC). Data were compared between the combo and REISAMIC cohort using the Fisher’s exact and CHI2 tests (α = 5%). Results Overall, 83 pts receiving a combo of anti-PD(L)1 plus AA and 484 pts treated with anti-PD(L)1 were included. Both cohorts were similar for baseline characteristics: sex ratio, age, weight. Main tumor types in single anti-PD(L)1 vs combo were (in %): renal cell carcinoma, 5 vs 37; urothelial carcinoma, 3 vs 4; thoracic (lung or mesothelioma), 45 vs 32; gynecologic, 1 vs 8. The KS score was heterogeneous. It found 334/484 (69%) pts at intermediary or high risk of TE in the REISAMIC cohort and 70/83 (84%) in combo cohort (p = 0.006). In REISAMIC cohort, TE incidence was 7% compared to 18% in the combo cohort (p value=0.0006). Conclusion These results suggest that pts treated with combo AA plus anti-PD(L)1 seem to be more at risk of developing TE compare to single therapy anti-PD(L)1, according to a KS higher in this cohort. Further prospective study're warranted to investigate the risk of TE in pts receiving AA plus anti-PD(L)1 and to investigate the benefit of preventive anticoagulants therapy. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitor therapy is showing marked efficacy in advanced non-small cell lung cancer (NSCLC). Meanwhile, it is concomitant with distinctive immune-related adverse effects. We aim to describe the incidence of pneumonitis and other rare but severe immune-related adverse effects (IRAEs), as well as treatment related deaths. In addition, we analyze the differences in incidence of pneumonitis between PD-1 and PD-L1 inhibitors and standard-of-care chemotherapy. Methods PubMed was searched up to 24 March 2017 for clinical trials of PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, avelumab and durvalumab) in treatment of NSCLC. Besides, references of relevant articles were screened. Results Finally, 22 trials were included in our study, 14 with data of pneumonitis, 19 with other severe IRAEs or treatment related deaths and 5 with control groups. Incidence of all-grade pneumonitis was 2.9% (95% CI, 2.0-4.8%) and grade 3 or higher pneumonitis 2.0% (95% CI, 1.0-2.0%). Incidence of all-grade pneumonitis in PD-1 and PD-L1 inhibitor therapy (n=1,313) was significantly higher than that in chemotherapy (n=918) (OR=2.35, 95% CI, 1.32-4.20, P=0.004), but had no significance in grade 3-5 pneumonitis. Incidence of cardiorespiratory arrest (n=537) was 1.0% (95% CI, 0-2.0%), cardiac failure (n=214) 2.0% (95% CI, 1.0-5.7%), myocardial infarction (n=402) 1.0% (95% CI, 0-3.8%), stroke (n=135) 2.0% (95% CI, 0-13.0%), disease progression (n=391) 1.0% (95% CI, 0-2.9%), pancreatitis (n=700) 1.0% (95% CI, 0-2.0%) and severe skin reactions (n=836) 2.0% (95% CI, 1.0-3.8%). Incidence of treatment related deaths was 0.7%. Conclusions Immune related adverse effects can on occasion be life-threatening even though usually rare. Incidence of pneumonitis in PD-1 and PD-L1 inhibitors was significantly higher than that in chemotherapy. More studies should be conducted to investigate the incidence of these rare but life-threatening IRAEs.

Background: Patients (pts) with NHL experiencing early relapse (ER) within two years of initial diagnosis and those double refractory (DR) to both rituximab and chemotherapy have particularly poor outcomes (Casulo et al JCO 2015; Gopal et al. NEJM 2014). Preliminary results from CC-122-NHL-001, the first study of CC-122, a novel cereblon-modulating agent, in combination with obinutuzumab (G), showed promising response rates in pts with R/R B-cell NHL (Michot et al Blood 2016). Herein, we report updated results for safety and efficacy from CC-122-NHL-001 (NCT02417285) with further 12 months follow up. Methods: CC-122 was given orally (5/7 d) for 28-d cycles in escalating doses plus a fixed dose of intravenous G 1000 mg on d2, 8, 15 of cycle 1 (c1) and d1 of c2–8. CC–122 active ingredient in capsule formulation (AIC) 1, 2, 3, and 4 mg and CC-122 formulated capsules (F6) 3 and 4 mg were evaluated in separate cohorts. Primary end points included safety and tolerability, NTD, and MTD. Response was assessed using the Cheson 2007 criteria every 2 cycles to c6, every 3 cycles to c12, and every 6 cycles thereafter. Results: As of September 1, 2017, 44 pts with R/R B-cell NHL were enrolled in the dose-escalation phase. Tumor types included 19 pts with DLBCL, 24 with FL, and 1 with MZL. Median age was 60 y (range, 26–81 y), 29 (66%) were men, and 33 (75%) had stage III/IV disease. Median number of prior anticancer therapies was 3 (range, 1– 11), and 18 pts (41%) had 1 prior ASCT; 2 pts had a dose-limiting toxicity (grade 4 neutropenia, n ¼ 1 [CC-122 AIC 3 mg]; grade 5 tumor flare, n ¼ 1 [CC-122 F6 4 mg]). The most common (15%) grade 3/4 TEAEs were neutropenia (52%) and thrombocytopenia (25%). ORR/CR rate in the total population was 68%/27% (DLBCL, 47%/11%; FL, 84%/42%). The mDOR was 19.4 mo (95% CI:7.9, NR). Subgroup analysis showed comparable mPFS and DOR for high-risk (ERþDR) and standard-risk FL pts (mPFS, 21.1 mo [2.9, NR] vs 16.2 mo [1.7, 16.2]; DOR, 19.3 mo [1.9, NR] vs NR). Conclusions: CC-122þG is well-tolerated, with promising response rates and durable remissions in R/R B-cell NHL. Subgroup analysis showed CC-122þG has similar efficacy in the high-risk and standard-risk FL population

Background The use of immune checkpoint inhibitors (ICI) has revealed a new panel of tumor response and adverse events. Immune-related sarcoidosis-like reactions is frequently misdiagnosed as progressive or recurrent disease. This study aims to decipher the diagnosis hallmark of immune-related sarcoidosis-like reactions as well as its association with patients’ outcome. Methods From August 2014 and December 2018, in a centralized single center review, we retrospectively included all patients with histologically proven immune-related sarcoidosis-like reaction during a treatment with ICI in monotherapy or combination. 54 variables were retrospectively recorded: clinical (n = 17), biological (n = 11) and radiological (n = 26), as well as the objective response to treatment using the best overall response according to iRECIST. Results Out of 3,200 patients treated with ICI, a total of 18 histologically proven sarcoidosis were diagnosed. The majority were female patients (n = 11/18) treated for melanoma (n = 14/18) or clear renal cell carcinoma (n = 3/18). The median [range] time to diagnosis of a sarcoidosis-like reaction was 30 [5-126] weeks after ICI treatment initiation. On CT-scans, the most common radiological findings were: absence of radiographical progression of the primary tumor per RECIST1.1 (100%), bilateral symmetrical mediastinal lymphadenopathy (100%), symmetrical hilar lymphadenopathy (84%), and micronodules with lymphatic distribution (15%). On PET-CT, an extrathoracic glucose uptake was observed in 65% of patients. The sites involved were pleural involvement, abdominal lymph nodes, liver, and spleen. Patients with immune-related sarcoidosis-like reactions were objective responders according to iRECIST in 84% (n = 15/18) of patients, while only 15% had stable disease. Conclusions Immune-related sarcoidosis is characterized by the appearance of new mediastinal and/or pulmonary lesions, usually at 30 weeks after initiation of treatment, with stability of baseline target lesions. PET/CT demonstrated extrathoracic uptake in 65% of patients. This should not be misinterpreted as disease progressive since 84% of patients will show an objective response to ICI. Legal entity responsible for the study Ammari Sami. Funding Has not received any funding. Disclosure S. Champiat: Advisory / Consultancy: Astrazenaca; Advisory / Consultancy: BMS; Advisory / Consultancy: Janssen; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche. J. Michot: Advisory / Consultancy: BMS. All other authors have declared no conflicts of interest.

Background The adverse events generated by immunotherapies are characterized by their wide diversity, unpredictability and reversibility by steroid used, and requires a delicate management. A collaborative organization of immunological toxicology management called ImmunoTOX (iTox) has been set up at Gustave Roussy to support physicians in their routine practice. Methods Descriptive study of all consecutive advice given by the ImmunoTOX committee at Gustave Roussy from Apr 6, 2016 to Jan 2, 2019. The iTox committee organizes a multidisciplinary meeting twice a month with organs specialists, oncologists, pharmacovigilants, radiologists, around prescribing physicians facing difficult to manage or unusual immune related adverse events (irAEs). Results The iTox committee delivered 398 pieces of advice for 356 patients (207 men and 149 women) receiving immunotherapies. Patients received anti-PD1 (55%) or anti-PDL1 (6%) given in monotherapy, or in combination with anti-CTLA4 (11%), or in combination with targeted therapy (11%), or another immunotherapy regimen (17%). The queries patterns for advices questioned the causal link (37%), rechallenge over G ≥ 3 (27%), or a complex clinical management (25%) or the possibility of initiating immunotherapy in a patient with comorbidities (10%). The iTox committee retained a causal link between the adverse event and immunotherapy in 273 of the 356 patients (77%). Of these 273 patients with irAEs, the grade of maximum severity was grade 1-2 in 112 (41%), grade 3-4 in 148 patients (54%), and irAE ultimately resulted in death in 13 (5%) patients. The organ categories mostly involved by requests were lung (21%), gastrointestinal (13%), liver (12%), musculoskeletal (10%) and neurological (8%). Over the study period, the 273 patients with irAEs led to 313 requests for advice that recommended systemic corticosteroids (n = 193, 62%) or a second immunomodulatory agents (n = 45, 14%). Conclusions These results should help cancer hospitals to further appreciate the current medical needs in their management of irAEs. By a specific management, patients with autoimmune comorbidities and rechallenge over G ≥ 3 could be regarded as precautions for use and not absolute contraindications. Clinical trial identification Commission Nationale de l’Informatique et des Libertes N°2098694v0. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure J. Michot: Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Cellgene; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Honoraria (institution): Abbvie; Honoraria (institution): Xencor. J. Soria: Full / Part-time employment: MedImmune. C. Massard: Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (institution), Advisory / Consultancy, Leadership role: Lilly. All other authors have declared no conflicts of interest.

Background Anti-PD1 and anti-PD-L1 are effective checkpoints inhibitors to stimulate the immune system against many types of cancers. The flip side of these immunotherapies is the generation of immune-related adverse events (irAE), which can theoretically affect all organs including muscle tissue. Immune-related creatine phosphokinase (irCPK) increase is associated with immune related myositis. The meaning of CPK monitoring in clinical practice remains poorly understood. In this observational study, all the grade ≥ 2 increased CPK occurring in patients treated with anti-PD-1 or anti-PD-L1 were investigated to determine their clinical significance. Methods All consecutive pts treated with anti-PD1 or anti-PD-L1, in monotherapy or in combine therapy with other agents, monitored by routine CPK in the Drug Development Department (DITEP) and in the Dermatology Unit of Gustave Roussy between January 2016 and December 2018 were retrospectively reviewed. Patients CPK monitoring level were extracted from biological chart and all the patients with grade ≥ 2 increased CPK were selected for the analysis. Results Among the 1151 patients treated with anti PD1/PD-L1, 53 (4.6%) had grade ≥ 2 increased CPK regardless of immune causality and 31 (2.7%) had a grade ≥ 2 irCPK increase. Among the 53 pts with CPK increase, mean age was 54 years old, tumor types were skin (n = 21), bladder and urothelial (n = 5), head and neck (n = 4) and others (n = 23). CPK increase was not related to the treatment in 22 (41%) pts, was immune-related to anti-PD1/PDL1 and not clinically significant in 19 (36%) pts, was immune-related with muscular adverse events in 10 (19%) pts, including 2 myositis and 2 acute polyradiculoneuritis; and was immune-related with myocarditis in 2 (4%) pts. The mean of CPK maximal peak was significantly higher in patients with immune-related cardiac or muscular adverse event that in the asymptomatic CPK increase pts (1271 UI/L vs. 771 UI/L, p-value = 0.02). Conclusions The frequency of grade ≥ 2 irCPK increase is estimated at 2.7% of patients treated with anti-PD1 or anti-PD-L1. For patients treated with anti PD1/PD-L1, regular CPK monitoring appears as clinically relevant in the early detection of immune-related cardiac and muscular adverse events. Legal entity responsible for the study Jean-Marie Michot. Funding Has not received any funding. Disclosure C. Baldini: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. P. Romano-Martin: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. P. Vuagnat: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. S. Champiat: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. A. Varga: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. A. Hollebecque: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. C. Robert: Advisory / Consultancy: Roche, BMS, MSD, Amgen, Novartis. C. Massard: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. O. Lambotte: Advisory / Consultancy: BMS, MSD, AstraZeneca, LFB, CSL Behring, Janssen. J. Michot: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. All other authors have declared no conflicts of interest.

Background: Treating relapsed/refractory lymphoma remains a challenge. While phase 1 trials classically aim to determine the recommended phase 2 dose (RP2D), the search of anti-tumor activity is increasingly evaluated. We aimed to assess the tolerance and efficacy of phase 1 trial and to determine a simple scoring system to identify patients who will prematurely discontinue phase 1 studies (before six weeks), in a large cohort of patients with relapsed/refractory lymphoma. Patients and Methods: Data from 105 consecutive patients with relapsed/refractory lymphoma treated within a panel of 17 phase 1 trials were collected, between 2008 and 2014. At inclusion, median age was 66 years [range: 23-83]. Lymphoma histological patient's types were: 58 (55%) aggressive non-Hodgkin lymphoma (34 diffuse large B-cell lymphoma, 7 T-cell lymphoma and 17 Mantle cell lymphoma), 31 (30%) indolent non-Hodgkin lymphoma and 16 (15%) Hodgkin lymphoma. The predefined Gustave Roussy (GR) score combined two simple variables, PS and baseline serum albumin (+1 if PS = 0, +1 if albumin ≤ 35g/l). Results: Grade 3 or 4 adverse events were experienced by 40/105 (38%) patients. With a median follow-up of 10 months, median OS and progression free survival (PFS) were respectively 19 (CI95%: 12-37) and 4 (CI95%: 2-5) months. Best overall response rate and disease control rate were 22% and 56%, respectively. Histological type's analysis shown median OS was 10, 45 and 47 months in aggressive-NHL, Hodgkin and indolent-NHL, respectively (p 0, baseline albumin ≤ 35 g/l and baseline LDH ≥ 250 UI/L were significantly associated with poorer OS. Patients with a GR score = 0 experienced significantly better OS compared to patients with a score = 1 and a score = 2 (37 months vs 17 months vs 9 months; p = 0.007). A premature study discontinuation was recorded in 28/105 patients (27%). The GR score distinguishes patients most likely to remain on study for more than 6 weeks. Conclusion: The three parameters WHO performance status (PS) > 0, baseline albumin ≤ 35 g/l and baseline LDH ≥ 250 UI/L are associated with OS and premature withdrew of study. Both PFS and OS survival curves demonstrates a plateau, in favor of therapeutic effect potentially maintained.