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Background: The widespread use of immunotherapy drugs in the oncological field has led to the spread of new toxicities compared to the more common chemotherapy treatments. This is because immunotherapy with anti-CTLA-4 (Cytotoxic T Lymphocytes-Associated Antigen 4), anti- PD-1 and anti-PD-L1 monoclonal antibodies has become the standard-of-care in a growing number of indications. Any organ or tissue can be involved, but more commonly, side effects are reported regarding skin, colon, endocrine glands, liver, lung and kidney. Other less frequent, but more serious, adverse events are neurological and myocarditis. Methods: We performed an electronic search on PUBMED of the literature concerning immunotherapy- related toxicities and their management in oncological patients from 2007 to 2020, with particular attention to the most recent publications. Aim: To summarize the different types of immunotherapy-related toxicities, together with their incidence and diagnosis, and to simplify their management, especially in the emergency setting. Conclusion: Usually, for grade I toxicities, it is not recommended to stop immunotherapy; for most of grade II toxicities, immunotherapy should be postponed to when toxicity will have regressed to grade I, considering the possibility of corticosteroid treatment for most toxicities. The majority of grade III and IV require administration of high-dose corticosteroid intravenous therapy and suspension of immunotherapy. related to immune checkpoint inhibitors’ toxicity, occurring at a rate of 0.3-1.3%, is well below fatality rates due to other oncologic interventions and should not discourage the promising results so far reached by immunotherapy.

e14566Background: CIT is provided with a platelet count < 100×109/μL with or without bleeding in cancer patients receiving chemotherapy .CIT can prevent the administration of the optimal dose and s...

Germline mutations of the tumour suppressor gene BRCA1 are involved in the predisposition and development of breast cancer and account for 20-45% of all hereditary cases. There is an increasing evidence that these tumours are characterised by a specific phenotype and pattern of gene expression. We have hypothesised that differences in chemosensitivity might parallel molecular heterogeneity of hereditary and sporadic breast tumours. To this end, we have investigated the chemosensitivity of the BRCA1-defective HCC1937 breast cancer cell line, and the BRCA1-competent MCF-7 (hormone-sensitive) and MDA-MB231 (hormone-insensitive) breast cancer cell lines using the MTT assay. The 50% inhibitory concentration (IC(50)) for the individual compounds were derived by interpolate plot analysis of the logarithmic scalar concentration curve after a 48 h exposure. HCC1937 cells were significantly (P0.005) more sensitive to cisplatin (CDDP) (IC(50) : 30-40 microM) compared with MCF-7 (IC(50) : 60-70 microM) and MDA-MB231 (IC(50) : 90-100 microM) cells. On the other hand, BRCA1-defective breast cancer cells were significantly less sensitive to doxorubicin (Dox) (IC(50) : 45-50 microM) compared with MCF-7 (IC(50) : 1-5 microM) and MDA-MB231 (IC(50) : 5-10 microM) (P0.02), as well as to paclitaxel (Tax) (IC(50) :2 microM for HCC1937, 0.1-0.2 microM for MCF-7 and 0.01-0.02 microM for MDA-MB231) (P0.001). Full-length BRCA1 cDNA transfection of BRCA1-defective HCC1937 cells led to the reconstituted expression of BRCA1 protein in HCC1937/(WT)BRCA1-derived cell clone, but did not reduce tumour cell growth in soft agar. BRCA1 reconstitution reverted the hypersensitivity to CDDP (P0.02), and restored the sensitivity to Dox (P0.05) and Tax (P0.001), compared with parental HCC1937 cells. Taken together, our findings suggest a specific chemosensitivity profile of BRCA1-defective cells in vitro, which is dependent on BRCA1 protein expression, and suggest prospective preclinical and clinical investigation for the development of tailored therapeutical approaches in this setting.

Chemotherapy-induced-thrombocytopenia (CIT) can prevent the administration of the optimal dose and schedule of anticancer treatment and limit its benefits in the adjuvant or metastatic setting. Therapeutic approaches will include dose delays or reduction ,platelet transfusion and consideration of platelet-stimulating agents. In a review of chemotherapy-induced thrombocytopenia including >47 000 patients with solid tumors, CRC was associated with the highest prevalence of thrombocytopenia by cancer type, and most patients had received a platinum-based chemotherapy regimen. Experimental data demonstrated that Platinum is one of the heavy metals which may induce immune manifestations in humans and in experimental animals. However, novel mechanisms of oxaliplatin-related thrombocytopenia have been implicated and include an immune-dependent mechanism, as well as portal hypertension related to sinusoidal injury yielding splenic sequestration of platelets. Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has been shown efficacy and safety in chronic immune thrombocytopenia (ITP) patients not responding to previous therapy .Moreover,some clinical studies demonstrate a role for thrombopoietin agonists in improving compliance with cytotoxic regimens in cancer patients whose chemotherapy was delayed due to thrombocytopenia,[and they suggest that prophylactic use of eltrombopag or romiplostim might reduce the degree and duration of chemotherapy-induced thrombocytopenia. Here, we report on a series of 22 patients at high risk of CIT because of platinum chemotherapy schedules who received low doses eltrombopag as prophilaxis .The aim of the study was to prevent CIT in patients who cannot be supported by platelet transfusions and for whom the maintenance of dose intensity is crucial for remission or survival Methods A total of 22 consecutive adult patients, female (60 %), median age 47 years (range 28 - 67) were enrolled in the study. The reason of chemotherapy has been ovary cancer in 5 patients, colon cancer in 8 patients, relapsed DLBC lymhoma in 4 patients,, TNBC in 2 patients, pancreatic cancer in 3 pts. All patients received eltrombopag 25 mg by mouth twice a weekly as soon as the platelet count falls below 80000 mmc, and continued on treatment until completion of cycles of chemotherapy. Results The mean platelet count nadir was 60000 mmc; the number of days with platelet count < 80000/µL was 4 days; The maximum value reached was 270,000 mmc. No treatment-related toxicity was observe. 1 out of 22 pts , did not respond to the planned dose and received 50 mg for eight consecutive days before each course of chemotherapy.The principal endpoints of the study : avoid nadir platelet counts < 50,000/µL,platelet transfusions, bleeding events, chemotherapy dose reductions , chemotherapy delays. were achieved in all patients. Conclusion In our opinion low dose eltrombopag prophilaxis can be an effective and safe strategy for preventing the CIT. Disclosures No relevant conflicts of interest to declare.

e22539Background: Kaposi's sarcoma (KS) is a potentially life-threatening multifocal neoplasm that may represent a difficult therapeutic challenge in disseminated stages. Liposomal anthracyclines, or combination chemotherapy are widely used to treat this kind of patients.. The efficacy of taxanes (paclitaxel and docetaxel), as agents with antiangiogenic properties,has been described previously in the treatment of KS patients but the length of the infusion, the need for pre-medication with steroids and toxicity caused by solvents can limit their utilization , especially in elderly patients. Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication which can make it easier to tolerate .At the moment there are no studies on its efficacy and safety in older KS patients . Methods: After written informed consent was obtained a phase II trial was conducted with nab-paclitaxel in 6 patients with advanced-stage KS to assess its safety and antitumor activity. The mean ...

Introduction. Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has been shown efficacy and safety in chronic immune thrombocytopenia (ITP) patients not responding to previous therapy , by raising the platelets count in both continued long-term administration and in a repeated short-term administration. However, when eltrombopag is discontinued, platelet counts usually return to baseline within 2 weeks. As reported in different case series only 15 % of patients achieve a durable response after treatment discontinuation. The aims of this study was to evaluate the efficacy and safety of eltrombopag given at a dose of 25 mg every 3 days as maintenance therapy in responding patients after an initial standard dose of 50 mg orally once daily. Methods. A total of 7 consecutive adult patients, female (70 %), median age 47 years (range 28 - 79) were enrolled in the study. Patients had ITP for a median of 3.5 years and had failed a median of four prior therapies. Splenectomy was not taken into account because contraindicated or refused. All patients received eltrombopag 50 mg by mouth once a day as induction treatment .A complete blood count was performed at baseline, on day 5, then weekly for 28 days, every 2 weeks during maintenance. Complete Response ( CR) was defined as platelet count ≥ 100 * 10^9/L measured on two occasions > 7 days apart and the absence of bleeding. Relapse Free Survival (RFS) was considered to be from the day of initial response until relapse (Plt Results. 7 out of 7 pts achieved CR after eltrombopag induction therapy and were enrolled in the study. 1 out of 7 pts was too early to be evaluated. 6 pts were eligible for the maintenance phase. The median (range) follow-up of this case series was of 13.5 months (4-22), during which all patients maintained a safe platelet count without the need to increase the dose or frequency of administration. No patient relapsed . No adverse events were observed. Conclusions. Maintenance therapy was manageable and well-tolerated. Maintenance can allow for improved health care resource allocation providing cost savings and potentially improves patients' quality of life by by reducing the need of food restriction/dairy products required when taking eltrombopag.Moreover , maintenance therapy improves adhesion to the treatment and may be an effective alternative for patients who can not discontinue the drug Disclosures Abruzzese: novartis, bristol myers squibb, ariad, pfizer, takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Introduction. Immune thrombocytopenia (ITP) is characterized by platelet destruction due to the presence of platelet antibodies. This phenomenon is associated with impaired platelet production by bone marrow. Short-course corticosteroids and high-dose intravenous immunoglobulins remain the first-line treatments. Aim of this study was to test if SCIG is equally effective and can be less expensive than hospital-based IVIG in treating chronic-ITP Methods Seven-ITP patients aged between 13-52 years were given liquid intravenously immunoglobulin (IVIg) stabilized with proline in a dose of 400 mg/kg per day for 5 consecutive days.The median time since ITP diagnosis was 18 months (range, 16 – 38) Median (range) baseline platelet count 19 (3 – 32) x 109/L.,median of 2 (1 – 3) prior ITP therapies. Furthermore, none of of the subjects was a good candidate for TPO-receptor agonists (romiplostim and eltrombopag) because of age or other comorbidities.6 / 6 had a good response to the first 5 day course of gammaglobulin therapy, (platelet count ≥50 × 10(9) /l and ≥2× baseline). The peak platelet count occurred within 7 days from the beginning of the therapy. Only in one patient the platelet count peak took place after 12 days. During the first year of treatment, only one of seven initial responder patients achieved CR(defined as platelet count ≥ 100 * 10^9/L measured on two occasions > 7 days apart and the absence of bleeding) and was excluded from the study. After a loading dose of 2 g/kg over 2 days of IVIg, home SCIG of 8 gr total weekly dose was started by 87,3% (6/7) to maintain platelet counts in the target range of 50–100x109/L. Results 5/6 patients reached the target. One patient achieved CR during the maintenance therapy.No untoward reactions necessitating cessation of therapy were encountered during this study. The most common side effect observed was headache. Conclusion Application of SCIG was well tolerated, easy to manage, and led to stabilization of the disease course.The therapy facilitates home therapy, as the infusion technique is easy for children, adults and elderly people to learn and there is no need for venous access. SCIG home therapy leads to significantly improved life situations for the patients; the SCIG home therapy regimen in particular reduces the costs of treatment. Overall costs per patient were strongly reduced in SCIG in comparison to IVIg.SCIG may represent an effective new therapeutic option in chronic ITP. Disclosures Abruzzese: novartis, bristol myers squibb, ariad, pfizer, takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Abstract 4665 Introduction The thrombopoietic growth factors (TGFs) are a novel class of compounds for the treatment of chronic immune thrombocytopenia (ITP). The first of these agents to receive regulatory approval, romiplostim and eltrombopag, have demonstrated impressive efficacy and tolerability in randomized controlled trials and open-label extension studies of several years duration and stand poised to revolutionize the management of ITP. Nonetheless, critical questions regarding the safety of these agents, remain partially unanswered. The aim of this report is to focus on the incidence of thrombocytosis and rebound thrombocytopenia mimicking cyclic thrombocytopenia in a series of 15 patients treated with romiplostim in a single institution. Methods 15 patients (8 M and 7 F, median age 45 years range 21–76) with chronic ITP (median onset 6 years, range 1–11), 1/15 splenectomized, plts median 2 ×109/L, (range 18–24) were treated with Romiplostim initial dose of 1 mg/kg, weekly checks, with only weekly increase of 1 mg/kg to reach a platelet count ≥ 50 × 109/L. The target platelet count range was 50 to 250 × 109/L. Twenty-two percent of patients (3/15) were receiving concurrent treatment for ITP (corticosteroids, danazol) at the time of first romiplostim dose. These medications were discontinued after platelet counts reached 50 × 109/L. Results A platelet response had been achieved by 30% of patients after the first dose and by 51% of patients after the third dose. Treatment response was observed in 100% of pts treated after 6 weeks. In three patients after the eighth week, with average values plts 120×109/l, the subsequent administration of the drug led to an increase in platelet count > 1000×109/l, with rapid fall to Conclusion According to an analysis of all patients with ITP treated with romiplostim in 4 controlled trials have been reported 3 thrombocytosis events in 271 pts (1.1%). In our series the percentage was 20% (3/15), much higher than that reported in the literature, with no thrombotic complications related. Interesting in a case CR was still maintained at 8 months of follow-up despite cessation of treatment. It would be very useful to create a network of information between users of romiplostim to evaluate on a larger series, the true incidence of thrombocytosis and any related thrombotic phenomena associated in a day by day clinical practice. Disclosures: No relevant conflicts of interest to declare.

e18556 Background: Waldenstrom macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder characterized by lympho plasmacytic bone marrow infiltration along with an immunoglobulin M (...

Abstract 4401 Background Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder characterized by lymphoplasmacytic bone marrow infiltration along with an immunoglobulin M (IgM) monoclonal gammopathy. Asymptomatic patients with monoclonal IgM and without morphologic evidence of bone marrow infiltration < 10% clonal marrow cells) are classified as having IgM-MGUS.Therapy is postponed for asymptomatic patients, and progressive anemia is the most common indication for initiation of treatment. Resveratrol (3,4',5-tri-hydroxy-trans-stilbene) is an antioxidant constituent of a wide variety of plant species including grapes. It has gained considerable attention because of its anticancer properties, as shown in solid and hematologic malignancies. Published data show that resveratrol has significant antitumor activity in WM cells line. Moreover, simvastatin, a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, induced inhibition of proliferation, cytotoxic effect and apoptosis in IgM secreting cell lines as well as in primary CD19(+) WM cells. With this background we have treated 4 patients with asymptomatic WM with an association of simvastatin and resveratrol to test the efficacy of such of drugs in asymptomatic Waldenstrom macroglobulinemia Methods 4 pts (3 males and 1 female), median age 42,3 yrs (range, 42–73) and asymptomatic WM were treated with a schedule containing resveratrol 40 mg/die and simvastatin 20 mg/die for at least 90 days. At enrollment patients characteristic were hemoglobin level median, 12.1 g/dL,serum beta(2)-microglobulin level median, 2.4 mg/L, and IgM peaks median, 1.8 g/dL. All patients have taken regularly the drugs and there have been no adverse events.CK and LDH serum levels were kept in the normal range. Results In all IgM-MGUS patients a reduction of more than 50% of the IgM peak was observed after 3 months of therapy and it was still maintained at 12 months of follow-up. In SWM patient the reduction was about 25% and it was manteined over time. Striking, another patient with Waldentrom disease resistant to the previous therapy with EDX and anti-CD20 MoAb achieved a CR only after adding resveratrol and simvastatin. Conclusions Our data demonstrate clearly that the association between resveratrol with simvastatin decreases IgM secretion in Waldenstrom macroglobulinaemia and can be useful in asymptomatic or low risk patients not having any adverse effects. Disclosures: Off Label Use: Simvastatin showed in vitro activity on waldentrom cell lines Resveratrol showed in vitro activity on waldenstro cell lines.

Background: The management of AIHA, based mainly on empirical data and uncontrolled studies, relies principally on corticosteroids as a first-line therapy. Patients who are refractory or intolerant to these therapies (approximately 5–10% of the cases) constitute an important therapeutic challenge. The most frequent second-line options are splenectomy or immunosuppressive agents. Rituximab (R), an anti-CD20 chimeric monoclonal antibody being increasingly used in autoimmune disorders. Transfusion in patients with autoimmune hemolytic anemia generally is unwise, because the autoantibody in the serum usually reacts with the RBCs of all potential donors, making a satisfactory cross match impossible. Moreover, the erythroid response, can be inappropriately low, and several reports or senies’ have highlighted cases that have been associated with reticulocytopenia. Aim of this study is to test if the introduction of Rh-Epo in the refractory AIHA treatment may reduce the blood transfusion need and related risks Methods: 14 pts (M 7, F 7) median age 59.2 yr (range, 18–82) and AIHA resistant to standard treatment were treated with a schedule containing Rituximab, rh-EPO and prednisone (R-EP) 6 pts were idiopathic and the remaining 8 were associated with chronic lymphoproliferative syndromes (3), connective tissue diseases (2), primary antiphospholipid syndrome (APS)(1) and ulcerative colitis (2). mean Hb value and Ht at presentation were 6.3 g/dL ± 1.2, and 24 mL/dL, Median reticulocyte percentage was 9%, and median reticulocyte production index was 2.8 times basal. 24 % of cases had an initial reticulocyte count less than 4%, and 40% had an initial reticulocyte production index less than 2.0 times basal. These reticulocytopenic patients were prevalent in secondary cases. Serum erythropoietin level at baseline was (14 +/− 11 mU/mL)) Pts had altered hemolysis markers and direct antiglobulin test (DAT) was positive for both complement and IgG (IgA 1 pts). All cases had a bone marrow examination during hospitalization Erythroid hypoplasia was seen only in CLL pts.14/14 pts had serial reticulocyte measurements, Rituximab was administered intravenously at a dose of 375mg/m2 weekly for 4 weeks; prednisone 1 mg/Kg/day /for 30 days ; rh-EPO 30.000U/weekly for 4 weeks. Results: All pts completed treatment. No major infusion related side effects to R-EP were observed. Response criteria to R-EP were defined as follows: Complete Response (CR): Hb >10 g/dl or Hb increase >1.5 g/dl, resolution of symptoms of anemia, transfusion independent; Partial Response (PR): Hb > 9 g/dl or Hb increase of 1–1.5 g/dl. improvement in symptoms of anemia, transfusion independent; NR (failure to meet CR/PR). 100% were eligible for response. Responses were seen in 14/14 pts. CR in 13/14 and PR in 1/14, median follow up of 25.8 months (range 5–66 months). At the end of treatment DAT became negative in 12/14 pts, concentration of lactic dehydrogenase, total bilirubin and indirect bilirubin began to decrease at 12 days after the first dose of rituximab, and decreased to normal range after 22 days.. Three patients required packed red cell transfusions before starting R-EP and all became transfusion-free. A moderate hemolysis still persisted only in one patient. In the cases that were initially reticulocytopenic, reticulocyte production index rapidly increased, indicating a marrow erythropoietic response to REP Conclusion: Our experience demonstrates that R-EP is an effective and safe alternative for the treatment of refractory autoimmune hemolytic anemia. Awareness of the frequency of an initial reticulocytopenia in cases of autoimmune hemolysis may be important in initial diagnosis and treatment, because low reticulocyte production index may represent a lag in marrow responsiveness to hemolytic stress. Striking, the introduction of rh-Epo clearly avoids blood transfusions and overcame inappropriately low erythroid response in reticulocytopenic patients

18007 Background: Recently published data suggest that high doses of imatinib mesylate (IHD) (800 mg/daily) may be more effective than standard dose (400 mg/daily) in newly diagnosed Philadelphia c...

Background Recently published data suggest that high doses of imatinib mesylate (IHD) (800 mg/daily) may be more effective than standard dose (400 mg/daily) in newly diagnosed Philadelphia chromosome-positive chronic phase CML. Furthermore escalating the dose of imatinib to 800 mg per day can overcome some cases of resistance to imatinib but tolerability of high-dose imatinib continues to be an issue. Aims To evaluate the efficacy and safety of pregabalin dosed twice daily (BID) for relief of musculoskletal and neuropathic pain associated with IHD. Methods 13 patients in chronic phase (CP) were enrolled because complained of severe, persistent pain, requiring nonoppioid analgesics. Patients were asked to quantify their pain using a visual analogue scale (VAS) (numeric range 0–10). QoL assessment was based on Therapy Impact Questionnaire. At baseline, the median pain-rate was 5 (range 3–8). Pts received pregabalin in doses ranging from 75 to 300 mg twice daily for 12 weeks. Results Despite a short study duration, a significant reduction was seen in weekly pain score (p < 0.0001), as well as VAS score (p < 0.0001) allowed pts to receive the scheduled dose of imatinib. Pregabalin was well tolerated, and the most common adverse event was only somnolence. The short study duration precluded the assessment of longer term safety issues such as weight gain. Conclusions Pregabalin was safe and effective in decreasing pain associated with high dose of imatinib, and also improved mood, sleep disturbance, and quality of life.

8115 Background: Bisphosphonates are commonly used for metastatic bone disease in order to prevent skeletal-related events, to reduce bone pain and to improve quality of life. Zoledronic acid is commonly used in myeloma patients (pts), but additional studies are needed to determine the optimal timing, schedule and duration of treatment. Aim of the present study is to assess bone mineral density (BMD) in patients with high-risk MGUS and myeloma receiving zoledronic acid, using quantitative ultrasound analysis in transmission through phalanges. Methods: DBM Sonic Bone Profiler is the only ultrasound device that applies the method of signal analysis in transmission through phalanges. This technique has proven to be particularly effective in the diagnosis and treatment monitoring of post-menopausal osteoporosis. Measurements of BMD were performed by ultrasonography at distal metaphysis of the first phalanx of the II, III, IV and V hand finger, at baseline and at 1, 3, 6, 9, 12, 15 and 18 months. Results: 12 pts with high-risk MGUS (8 IgG k, 4 IgG lambda) and 4 pts with myeloma IIIA (3 IgG k, 1 IgA lambda), 6 males/ 10 females, median age 69 years, received zoledronic acid 4 mg intravenously every 4 weeks for at least 12 courses. All subjects took daily oral supplements containing elemental calcium (1 g) and vitamin D (400 IU). Myeloma patients also received chemotherapy. 4/6 males (66%) and 5/10 females (50%) improved amplitude-dependent speed of sound (AD-SoS) over the least significant change after 6 months. Mean difference from baseline value of AD-SoS shows a trend after 4 months of treatment, and became significant after 16 months (p No significant financial relationships to disclose.