INTRODUCTION:Anti-CD38 monoclonal antibodies (aCD38) are increasingly used in early lines of therapies in multiple myeloma (MM). Retreatment with aCD38-based regimen is a widely used practice in later lines. However, data coming from clinical trials are currently limited. EMMY is a noninterventional, prospective dynamic cohort study conducted in 73 centers in France to assess the real-life management of MM in France and which can explore the efficacy of aCD38-based retreatment. METHODS:Patients who initiated a second line of treatment with aCD38-based combinations after a first exposure to aCD38 were identified and described and the outcomes of progression-free survival (PFS) and overall survival (OS) were estimated. RESULTS:In the EMMY cohort, 286 patients received 2 lines of treatment including aCD38. For all aCD38-retreated patients, median PFS was estimated at 5.1 months. Median PFS was 23.6 m in patients sensitive to aCD38 and 4.6 in nonsensitive patients, P = .0003. Median OS was estimated at 17.3 months for all patients,14.8 months in patients nonsensitive to aCD38, and not reached (NR) in sensitive patients, P = .0004. No significant differences in PFS or OS were observed between the refractory and nonrefractory to aCD38 groups. CONCLUSION:These results of aCD38 retreatment in a large sample of real-life patients (n = 286) in extensively pretreated patients show that retreatment may be a meaningful strategy for aCD38 sensitive patients. These findings need to be investigated further while the use of aCD38 is emerging as a first-line treatment for newly diagnosed patients.

Objectives: The roles of procalcitonin (PCT) and C-reactive protein (CRP) in febrile cancer patients is currently unclear. Our aim was to assess these in febrile patients with solid tumors and to identify cut-off values for ruling out infection.Methods: We retrospectively evaluated patients with solid tumors admitted to hospital due to fever. They were divided into those with Fever with microbiologically documented infection (FMDI), Fever with clinically documented infection (FCDI) and Tumor-related fever (TRF). PCT and CRP levels were compared. Receiver-operating curves were plotted to define the best cut-off values for discriminating between infection-related and cancer-related fever.Results: Between January 2015 to November 2018, 131 patients were recorded (mean age 68 years, 67% male, 86% with metastasis). Patients with FMDI or FCDI had significantly higher baseline levels of PCT and lower CRP/PCT than those with TRF. A PCT cut-off value of 0.52 ng/mL for discriminating between infection and cancer-associated fever yielded 75% sensitivity, 55% specificity, 77% positive predictive value (PPV), and 52% negative predictive value (NPV). A CRP/PCT ratio with a cut-off value of 95 showed 56% sensitivity, 70% specificity, 79% NPV, and 44% PPV.Discussion: PCT is a sensitive marker of sepsis or localized infection in patients with solid tumors, but its specificity is poor. The CRP/PCT ratio improves specificity, thus providing a reliable means of ruling out infection for values above 95.

There is no standard of care for unresectable cutaneous squamous cell carcinoma (cSCC). Chemotherapy, alone or combined with radiotherapy, is commonly used mostly as palliative treatment; moreover, its poor safety profile limits its use most of the time, especially in elderly patients. Thus, alternative options are needed. Targeted molecular inhibitors, such as the epidermal growth factor receptor inhibitor cetuximab, seem promising, but data are limited. We retrospectively evaluated clinical outcomes of cetuximab as a single agent in this indication. The primary endpoint was the Disease Control Rate (DCR) at 6 weeks according to RECIST criteria. Secondary endpoints included DCR at 12 weeks, objective response rate (ORR) at 6 and 12 weeks, progression-free-survival (PFS), overall survival (OS), and safety profile. Fifty-eight patients received cetuximab as monotherapy. The median age was 83.2 (range, 47.4 to 96.1). The majority of patients was chemotherapy naïve. The median follow-up was 11.7 months (95% CI: 9.6-30.1). The DCR at 6 and 12 weeks was 87% and 70%, respectively. The ORR was 53% and 42%, respectively, at 6 and 12 weeks. The median PFS and OS were 9.7 months (95% CI: 4.8-43.4) and 17.5 months (95% CI: 9.4-43.1), respectively. Fifty-one patients (88%) experienced toxicity, and 67 adverse events related to cetuximab occurred. Most of them (84%) were grade 1 to 2. Our study shows that cetuximab is safe and efficient for the treatment of patients, even elderly ones, with advanced cSCC. These results indicate that cetuximab is a promising agent to test in new combinations, especially with immune checkpoint inhibitors such as anti-PD-1 agents.

Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020 The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints Results From April 4 to June 11, 2020, 1289 patients were analysed The most frequent cancers were digestive and thoracic Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died In multivariate analysis, independent factors associated with death were male sex (odds ratio 1 73, 95%CI: 1 18-2 52), ECOG PS ≥ 2 (OR 3 23, 95%CI: 2 27-4 61), updated Charlson comorbidity index (OR 1 08, 95%CI: 1 01-1 16) and admission to ICU (OR 3 62, 95%CI 2 14-6 11) The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1 53;95%CI: 1 00-2 34;p = 0 05) A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19 Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis

358 Background: Abiraterone acetate (AA), a CYP17A1 inhibitor, has been approved in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Germline polymorphisms in genes involved in androgen biosynthesis or transport may influence response and survival in this setting. Methods: ABIGENE is a multicentric prospective non-randomized pharmacogenetic study (NCT01858441). The primary objective was to investigate the association between 13 SNPs in genes related to AA pharmacology (CYP17A1, SLCO2B1 and SLCO2B3) and radiographic progression-free survival (rPFS), according to PCWG2 criteria, in pts with mCRPC treated with first-line AA + prednisone. The main secondary objectives were to evaluate the impact of these SNPs on radiographic and PSA response, overall survival (OS) and toxicity. SNPs were detected in blood samples before starting AA and analyzed by pyrosequencing or PCR-RFLP methods. Kaplan-Meyer’s curves with log-rank tests and cox regression models were used to identify relationships between SNPs and survival. Chi2 tests and student t-tests were used to identify association with response rate and toxicity. Results: 147 pts in 17 french centers were included between 2013 and 2017. Here are presented the results for the first 109 pts. The median follow-up was 28.7 months. Overall response rate (ORR) was 17%, and 74% pts had stable disease as the best response. Median rPFS was 10.9 months (95% CI 9.2-15.3). One SNP (rs10883782) in CYP17A1 was associated with rPFS on AA therapy (Table). Two other SNPs in CYP17A1 (rs4919683) and SLCO2B1 (rs1077858) were significantly associated with radiographic response. Data on PSA response, OS and toxicity will be presented at the meeting. Conclusions: This is the first prospective dedicated study to show an association between SNPs related to androgen metabolism and clinical outcome in mCRPC treated with AA. Clinical trial information: NCT01858441. [Table: see text]

e20035 Background: Rd is a treatment option for patients (pts) ineligible for transplant. Lenalidomide (R) pharmacokinetics (PK) has been evaluated in pts under 65 and very few data are available about PK, dosage safety and efficacy for pts older than 80. This retrospective study aimed to describe safety and efficacy of R in pts > 80 years. Methods: We did a retrospective study in 7 centers in France. Inclusion criteria were: pts > 80 with a MM treated with Rd. The primary outcome was Progression-Free Survival (PFS). Secondary outcome were PFS according to the dose of Rd, Overall Survival (OS), grade 3 and 4 toxicities. Results: 144 consecutive pts received Rd at a median age of 83.5 [80 ; 93.5]. Charlson score was 4 [2 ; 12]. A majority of pts (n = 103, 78%) had stage III MM (Salmon and Durie) at diagnosis and 13% (n = 16) had a clearance of creatinine < 40mL/min or/and creatinine > 173µmol/L. Median number of lines of treatment was 1 [0 ; 4]. Initial dose of R was 15mg [5 ; 25] ; 56 pts had a daily dose < 15mg and 80 ≥ 15mg. Median number of cycles of Rd was 8 [1 ; 64]. With a median follow-up of 23.2 months [1 ; 93] the 1 and 2-years PFS and OS were 72.1%/62.8% and 87.1%/78.5% respectively. At the end of follow-up 29 pts died (20%), 27 from myeloma, 0 from treatment toxicities. Complete response rate (CR), Strict CR, very good partial response, PR, stable disease and immediate progression were respectively of 8.8%, 2.2%, 20.4%, 51.8%, 9.5% and 7.3%. Rd was discontinued for progression in 63.9% of pts. 14.6% and 2.8% of pts had grade 3 or 4 toxicities respectively. 24 pts had another line of treatment after Rd. In univariate analysis, R dosage did not correlate with OS (p = 0.3), PFS (p = 0.8) or response. In multivariate analysis, the unique significant predictive factor associated with a worse OS was Hb < 10g/dL (p = 0.01). Conclusions: Rd is feasible in very old pts at a dosage of 15mg per day. Our results compare favorably with previous large prospective phase 3 study. In patients over 80, PK analysis seems to be mandatory to determine the adapted dosage.

Purpose: Few in vivo studies have been reported describing efficacy and duration of antibiotic lock therapy (ALT) with daptomycin (DPT) for long-term catheter-related bloodstream infections (CRBSI) due to coagulase-negative staphylococci (CoNS). We retrospectively analysed the efficacy of short-course ALT with DPT in combination with systemic treatment (ST) for CoNS-associated CRBSI in our hospital. Methods: Patients admitted for CoNS-associated CRBSI and treated with DPT as ALT and ST were retrospectively analysed. Success was defined as preservation of the catheter device 30 days after ending treatment. Catheter removal within 30 days of discontinuing treatment, for either microbiological documentation of CRBSI relapse or re-occurrence of unexplained fever, was considered as failure. Results: Among 7610 patients admitted to the Departments of Internal Medicine/Infectious Diseases and Pneumology in Cannes from January 2013 to November 2015, we identified 28 episodes of CoNS-associated CRBSI. Seven patients died of cancer during follow-up. Thus, 21 episodes were analysed among 20 patients (median age 67 years, 12 males, all treated for neoplasia and carrying a port-a-cath® device). Staphylococcus epidermidis was the main agent responsible for CRBSI. Median duration of systemic and ALT DPT was 3 days, in combination with rifampin for 4 days and then generally followed by a switch to oral drugs, most frequently cotrimoxazole or linezolid, to achieve 14 median days of treatment. Clinical success and failure rates were 76% and 24%, respectively. Conclusions: Short-course DPT as ALT, combined with 14 days of ST, allowed conservative management of CoNS-associated CRBSI in surgically implanted-catheters in three-fourth of cases.

Management of Acute Myeloid Leukemia (AML) in the elderly is particularly difficult as life expectancy is highly variable and the benefit-risk ratio of treatment depends on comorbidities and age-related pharmacological specificities.

BACKGROUND:We describe histological, clinical findings and outcomes of renal involvement during Leishmania infantum infection in four HIV-infected patients in South France and North Italy hospital settings.CASES PRESENTATION:Four HIV-infected Caucasian patients (age 24-49) performed renal biopsy during episodes of visceral leishmaniasis. They presented severe immunosuppression, frequent relapses of visceral leishmaniasis during a follow-up period of several years and partial or complete recovery of renal function after anti-parasitic treatment. Main clinical presentations were nephrotic or nephritic syndrome and/or acute renal failure secondary to membranoproliferative type III glomerulonephritis or acute interstitial nephritis. Clinical outcome was poor, probably as a consequence of insufficient immuno-virological control of the HIV infection.CONCLUSIONS:Our findings suggest that the main histological findings in case of renal involvement due to Leishmania infantum infection in HIV-infected patients are type III MPGN and acute interstitial nephritis, with a histological specificity similar to that observed in canine leishmaniasis. Poor immune status in HIV-infected patients, altering the capacity for parasite clearance, and prolonged course of chronic active VL in this population may lead to the development of specific renal lesions.

6633 Background: IT-Y90was approved in follicular lymphoma, and some data indicates that it could be used in DLBCL. It has been reported that early TEP-TDM negativity is associated with a longer survival in DLBCL, which suggest that these patients could benefit of a less intensive protocol. Methods: We conducted an international, open-label, phase II non-randomised study, in patients aged between 65 and 80 with age-adjusted (aa) IPI score of 0 and 1 and CD20+ DLBCL. The primary objective was to evaluate the efficacy of 3 cycles of RCHOP14 followed by, in case of complete response (CR), an injection of IT-Y90. Results: Thirty patients (M/F= 1) were included. Median age was 72.6 years (range 65 - 80). Patients had a stage III/IV, elevated LDH and IPI=1 in 38%, 16.6 and 57% respectively. 25 patients received the full treatment. Five obtained an uncomplete FDG-PET response and were excluded after 2 RCHOP cycles. 23 patients received the full IT-Y90 dosage (0.4mCi/Kg) and two received the attenuated dosage (0.3mCi/Kg). Mean treatment time was 54 days (median 52; min 48-max 69). The CR rate after RCHOP treatment was 85% [95% CI: 65-94]. No treatment-related deaths occurred. Grade III-IV neutropenia and thrombocytopenia was observed in 45% and 4%, respectively. Five patients experienced at least one febrile neutropenia. After IT-Y90, mean duration time for platelets <50G/l was 2.08 weeks (median 2; min 0-max 5). Two patients required platelet transfusion. With a median follow-up of 29.5 months [95% CI: 23-39], the estimated 3-year PFS was 90% [95% CI: 80-100] and the 3-year OS was 100% [95% CI: 100-100]. Among patients treated with 90Y-IT, only 3 relapsed were recorded (at 6, 16 and 24 months). Conclusions: this study suggested the feasibility, and efficacy of a short regimen including one injection of IT-Y90for selected DLBCL in complete response after 3 cycles of RCHOP14. This results need to be confirmed by further studies.

Objective: To assess the efficacy of capecitabine plus docetaxel (XT) versus epirubicin plus docetaxel (ET) as first-line therapy for metastatic breast cancer (MBC). Patients and Methods: Patients with no prior chemotherapy for MBC were randomized to 3-weekly cycles of either XT (capecitabine 1,000 mg/m2 twice daily, days 1–14; docetaxel 75 mg/m2, day 1) or ET (epirubicin 75 mg/m2, day 1; docetaxel 75 mg/m2, day 1). The primary endpoint was non-progression rate 6 months after randomization. The planned sample size was 106 patients based on a randomized, phase II selection design. Results: Between April 2004 and January 2007, 68 patients were randomized, giving 82% power to select the best regimen according to a 6-month non-progression rate. Slow accrual led to premature study termination. Baseline characteristics were generally well balanced between arms. The 6-month non-progression rates were 75.8% with XT versus 65.7% with ET (p = 0.36). After 42 months’ median follow-up, median progression-free survival was 12.4 versus 6.8 months, respectively (p = 0.040). The safety profiles were consistent with previous experience. Conclusion: Further larger studies are warranted to validate these results. Despite more grade 3 hand-foot syndrome, first-line XT may be a valid alternative to ET, potentially improving efficacy.

BACKGROUND. Docetaxel is a well-recognized drug in patients with hormone-refractory prostate cancer (HRPC), either alone or combined with estramustine. In this indication, a Phase If trial was conducted investigating a docetaxel-capecitabine combination.METHODS. Forty-six patients presenting with documented HRPC were enrolled in the study. The treatment regimen consisted of docetaxel (D) at a dose of 35 mg/m(2)/week (intravenously, 3 consecutive weeks) plus oral capecitabine (C) at a dose of 625 mg/m(2) twice daily (Days 5-18) every 28 days for 4 cycles. The primary endpoint was the biological response defined as a reduction in prostate-specific antigen (PSA) level >= 50%. Secondary endpoints were overall survival, safety, and quality of life.RESULTS. Thirty of 44 assessable patients (68.2%) achieved a biological response, 14 of whom (31.8%) normalized their PSA value. The median overall survival time was 17.7 months (95% confidence interval, 15.8 to not reached). Four treatment cycles were completed by 87% of the patients. Hematologic toxicity was mild. The main Grade 3-4 toxicities were cutaneous toxicity (13.1%) and changes in nails (6.5%). Physical functioning and role scales were higher before treatment (P =.02 and P =.003, respectively), fatigue and diarrhea were more frequent during and after treatment (P =.0003 and P =.03, respectively), and pain was lower during and after treatment.CONCLUSIONS. The results of the current study demonstrated the high efficacy of the DC combination in patients with HRPC, and the associated good tolerability This combination offers a new alternative to the docetaxel-estramustine combination. Further randomized trials are warranted.

4624 Background: Docetaxel monotherapy is active in hormone refractory metastatic prostate cancer. Pre-clinical models indicate a synergistic cytotoxicity between capecitabine and docetaxel. Recently, this association has proven survival benefits in advanced breast cancer. This multicenter phase II study reports on preliminary efficacy and safety data of docetaxel-capecitabine combination in hormone-refractory prostate cancer with metastases (HRPC). Methods: Eligible pts had histologically and biologically confirmed HRPC. Other requirements included a Karnofsky index of more than 50% and no prior chemotherapy except estramustine. Treatment consisted of 4 cycles of docetaxel 35mg/m2 on day 1, day 8, day 15 and capecitabine 1250mg/m2/day in 2 divided doses from day 5 to day 18 of each 28 days cycle. A minimum of 2 treatment cycles were required for response assessment. Biological efficacy was defined as a decline of >50% from baseline PSA levels. Clinical response was evaluated using RECIST criteria. Results: 23/50 planned pts were enrolled between June to November 2003. Patient baseline characteristics were: median age 69.5 years (range 51.4–81.3), median Gleason score: 8 (range 6–9), median PSA 73.2 ng/ml (range 0.93–2010.9). Sixty-height percent had prior radiation and 52.3% had prior surgical treatment. Disease related pain was present in 82.3% of pts. Pts received a median of 2 courses of treatment (range 1–4). A total of 54 cycles of treatment were administered. The most common grade (G) 3–4 toxicities included 1 G-3 anemia, 4 G-3 digestive toxicities and 1 G-3 stomatitis. Biological response was observed in 17 pts after the 2nd cycle and in 7 pts after the 4th cycle. Seven pts (41.2%) exhibited a PSA decrease of >50% after the 2nd cycle and 5 pts (71.4%) after the 4th cycle. Conclusions: This combination appears to be a very promising regimen with a favorable toxicity profile. These early encouraging data have to be confirmed with the analysis of the next 27 planned patients and final results will be presented at the meeting. No significant financial relationships to disclose.

PURPOSE To determine incidence of non-AIDS-defining cancers (NADC) in HIV-infected patients before (P1) and during (P2) the use of highly active antiretroviral therapy (HAART) relative to that observed in the French general population (FGP) of the same age and sex. PATIENTS AND METHODS Sex- and age-adjusted NADC standardized incidence ratios (SIR), with FGP as reference, were estimated in 1992 to 1995 (P1) and in 1996 to 1999 (P2) in a French Hospital Database on HIV prospective hospital cohort study. RESULTS NADCs were diagnosed in 260 patients during P1 and 391 patients during P2 among the 77,025 patients included in the database between January 1, 1992, and December 31, 1999. Estimated incidence of all cancers was higher in HIV-infected men than in FGP during both periods (P1 SIR = 2.36 and P2 SIR = 1.91). No excess of cancers was observed among HIV-infected women in either period. Incidence of all cancers did not change from P1 to P2 in either sex (SIR = 0.96 for men and 1.00 for women). In contrast, incidence of Hodgkin's disease (HD) was higher than in FGP in both sexes and both periods and increased in P2 as compared with P1; incidence of lung cancer was higher in both sexes during P2. CONCLUSION Relative to FGP, the overall incidence of NADCs was increased in HIV-infected men but not in women and did not differ between P1 and P2. Only HD was much more common in HIV infection, and the potential role of HAART on HD cannot be excluded.

This observation reports the case of a rapid paraparesia occurring in a young man. Imaging disclosed a spina tumor. Diagnosis of sarcoidosis leads us to suspect a specific spinal granuloma involvement and to start corticosteroid pulses. Clinical and radiological symptoms improved dramatically.