The aim of this study was to evaluate the impact of clinical variables and biologic features on response rate (RR), overall survival (OS) and progression-free survival (PFS) in 111 patients with de novo diffuse large B cell lymphoma (DLBCL). Fifty-three patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and 58 patients were treated with R-CHOP (rituximab + CHOP). The variables predictive of RR in the CHOP group were B symptoms, age, clinical stage, bone marrow involvement, bulky disease, International Prognostic Index (IPI) and Bcl-2; in the R-CHOP group, these variables were bulky disease, bone marrow involvement, IPI and Ki67 expression >80%. Multivariate analysis showed that in patients treated with CHOP, the independent prognostic factors associated with PFS were age, bulky disease, IPI and Bcl-2 and those associated with OS were performance status, clinical stage, IPI and bone marrow involvement. In contrast, in patients treated with R-CHOP, the variable shown by multivariate analysis to be an independent prognostic factor associated with PFS was bulky disease, whereas Ki67 expression >80% was associated with OS and PFS. Our data show that a high Ki67 expression and bulky disease could represent possible predictive factors of poor prognosis, which would help to identify a high-risk subgroup of newly diagnosed DLBCL.

No abstract

Recurrences of Hodgkin's Lymphoma (HL) 5 years after the initial therapy are rare. The aim of this study is to report a single centre experience of the clinical characteristics, outcome, and toxicity of pts who experienced very late relapses, defined as relapses that occurred 5 or more years after the achievement of first complete remission. Of 532 consecutive pts with classical HL treated at our Institute from 1985 to 1999, 452 pts (85%) achieved a complete remission. Relapse occurred in 151 pts: 135 (29.8%) within 5 years and 16 over 5 years (3.5%, very late relapses). Very late relapses occurred after a median disease-free interval of 7 years (range: 5–18). Salvage treatment induced complete remission in 14 pts (87.5%). At a median of 4 years after therapy for very late relapse, 10 pts (63%) are still alive and free of disease and 6 (37%) died (1 from progressive HL, 1 from cardiac disease, 1 from thromboembolic disease, 1 from HCV reactivation, and 2 from bacterial infection). The probability of failure-free survival at 5 years was 75%. The majority of deaths are due to treatment-related complications. Therapy regimens for very late relapse HL are warranted to minimize complications.

Despite the availability of several antiemetics, clinical findings show that control of chemotherapy-induced nausea and vomiting (CINV) continues to be a serious concern for hematological patients, mainly for those receiving multiple-day (MD) and high-dose (HD) chemotherapy (CT). For CINV prophylaxis, 5-hydroxytryptamine type-3 receptor antagonists (5HT 3 -RAs) and neurokinin 1 receptor antagonists (NK 1 -RAs) are usually administered together with dexamethasone, which may increase the risk of serious infections in patients undergoing myeloablative treatment. The rationale of this multicenter, openlabel and phase IIa study was to explore the efficacy of multiple doses of NEPA (netupitant/palonosetron) given as an everyother-day regimen without dexamethasone in preventing CINV in patients with relapsed-refractory aggressive non-Hodgkin's lymphoma (R/R-NHL), eligible for autologous stem cell transplantation (ASCT) and treated with MD-HD-CT. Seventy patients participated to the study. According to the adopted Fleming one-stage design, the primary endpoint of this study was achieved. The CR values were 87.1% (primary endpoint, overall phase: days 1-8), 88.6% (acute phase: days 1-6), and 98.6% (delayed phase: days 7-8), while complete control (CR with no more than mild nausea) was 85.7% (overall phase), 88.6% (acute phase), and 95.7% (delayed phase). Moderate and severe episodes of nausea were reported by less than 10% of patients in the overall phase and less than 5% in both the acute and delayed phases. Regarding safety, NEPA was well tolerated with only one adverse event (constipation) evaluated as possibly related to NEPA administration.In conclusion, our study demonstrated that multiple alternate dosing of NEPA without the addition of dexamethasone is highly effective for preventing nausea and vomiting in this difficult setting, with a good tolerability profile.

Purpose Prevention of chemotherapy-induced nausea and vomiting (CINV) is particularly challenging for patients receiving highly emetogenic preparative regimens before autologous stem cell transplantation (ASCT) due to the daily and continuous emetogenic stimulus of the multiple day chemotherapy. While studies have shown effective prevention of CINV during the conditioning phase with NK1 receptor antagonist (NK1RA)-containing regimens, there have been no studies evaluating antiemetic use during chemomobilization prior to ASCT. Methods This multicenter, open-label, phase IIa study evaluated the efficacy of every-other-day dosing of NEPA administered during chemomobilization in patients with relapsed-refractory aggressive non-Hodgkin’s lymphoma. Eighty-one patients participated. Results Response rates were 77.8% for complete response (no emesis and no rescue use), 72.8% for complete control (complete response and no more than mild nausea), 86.4% for no emesis, and 82.7% for no rescue use during the overall phase (duration of chemomobilization through 48 h after). NEPA was well tolerated with no treatment-related adverse events reported. Conclusion NEPA, administered with a simplified every-other-day schedule, show to be very effective in preventing CINV in patients at high risk of CINV undergoing to chemomobilization of hematopoietic stem cells prior to ASCT.

PurposePrevention of chemotherapy-induced nausea and vomiting (CINV) is particularly challenging for patients receiving highly emetogenic preparative regimens before autologous stem cell transplantation (ASCT) due to the daily and continuous emetogenic stimulus of the multiple day chemotherapy (MD-CT). While studies have shown effective prevention of CINV during the conditioning phase with NK1 receptor antagonist (NK1RA)-containing regimens, there have been no studies evaluating antiemetic use with MD-CT administered for mobilization of hematopoietic stem cells prior to ASCT. MethodsThis multicenter, open-label, phase IIa study evaluated the efficacy of every-other-day dosing of NEPA administered during MD-CT being given for mobilization of stem cells prior to ASCT in patients with relapsed-refractory aggressive non-Hodgkin’s lymphoma. Eighty-one patients participated. ResultsResponse rates were 77.8% for complete response (no emesis and no rescue use), 72.8% for complete control (complete response and no more than mild nausea), 86.4% for no emesis, and 82.7% for no rescue use during the overall phase (duration of MD-CT through 48 hours after). NEPA was well tolerated with no treatment-related adverse events reported. ConclusionNEPA, administered with a simplified every-other-day schedule, show to be very effective in preventing CINV in patients at high risk of CINV undergoing MD-CT for mobilization of hematopoietic stem cells prior to ASCT.

Cancer chemotherapy may be associated with a high incidence of nausea and vomiting (CINV), which may occur acutely within 24 hours after the start of chemotherapy (acute phase) or in the following days (delayed phase). Despite the availability of several antiemetics, clinical findings show that control of nausea and vomiting continue to be a serious concern for hematological patients, mainly for those receiving multiple-day (MD) and high-dose (HD) chemotherapy (CT), for which no specific international recommendations have been formulated, due to the lack of a unanimous consensus between the main international guidelines. NEPA is the first antiemetic developed as an oral fixed dose combination of two drugs that are antagonists of two receptors involved in the control of nausea and vomiting: a new highly selective NK1-RA, netupitant, and a second generation 5HT3-RA, palonosetron, that simplify the antiemetic regimen allowing for a lower number of capsules and days of treatment. In clinical practice, NEPA is administered together with dexamethasone that contributes to CINV prophylaxis by its intrinsic antiemetic properties. However, dexamethasone also exhibits an important immunosuppressive activity, which could lead to several adverse events, such as increasing the risk of serious infections, especially in patients undergoing myeloablative treatment. The rational of this study was to explore the efficacy of multiple doses of NEPA given with an every-other-day regimen without dexamethasone in preventing CINV in patients with non-Hodgkin's lymphoma (NHL) eligible for autologous stem cell transplantation (ASCT) and treated with MD-HD-CT. The chemotherapy regimen (BEAM/FEAM) was administered for 6 days, NEPA was taken on day 1, 3 and 5, and nausea and vomiting were monitored up to day 15. No dexamethasone was given for antiemetic prophylaxis. The primary endpoint was the percentage of patients achieving a Complete Response (CR; no vomiting and no use of rescue medication) during the overall phase, defined as the period from day 1 (first day of chemotherapy) until 2 days after the last dose of chemotherapy. Seventy patients participated to the study. According to the adopted Fleming one-stage design, the primary endpoint of this study was achieved. Indeed, the number of complete responders for the overall phase was 60, which is greater than the predetermined cut-off of 42, representing the minimum frequency of responders for which the treatment is considered effective. In addition to the primary efficacy result, several additional endpoints were evaluated for the study period (Figure 1). The CR values were 87.1% (primary endpoint, overall phase: days 1-8), 88.6% (acute phase: days 1-6) and 98.6% (delayed phase: days 7-8), while the complete control (CR with no more than mild nausea) was 85.7% (overall phase), 88.6% (acute phase) and 95.7% (delayed phase) (Figure 1A). Moreover, the percentages of patients that did not have any emetic episodes were 88.6% (overall phase), 90% (acute phase) and 98.6% (delayed phase) and patients that did not require a rescue therapy for controlling CINV were 94.3% (overall phase), 94.3% (acute phase) and 100% (delayed phase). Daily records taken from day 1 to day 15 showed that values for all these categories were above 85% for all the days of observation (Figure 1B). Patients also documented the grade of their nausea according to the Likert scale. Moderate and severe episodes of nausea were reported by less than 10% for the overall phase and less than 5% in both acute and delayed phase and the daily values of no nausea were above 65% for each day of the treatment (Figure 1C and 1D). Indeed, the mean patient global satisfaction for the antiemetic prophylaxis for the study period was 9.13 ± 1.59 out of 10. Regarding safety, a total of 12 Treatment-Emergent Adverse Events (TEAEs) occurred in 6 (8.6%) subjects enrolled in the study. Among these, only 1 (8.3%, constipation) was evaluated as possibly related to NEPA administration. Moreover, the only two TEAEs classified as SAE (Serious Adverse Event) were two episodes of fever that have been evaluated as not-related to NEPA. Therefore, the safety profile of NEPA was confirmed also in this setting. In conclusion, our study demonstrated that multiple alternate dosing of NEPA without the addition of dexamethasone can effectively prevent nausea and vomiting in a difficult setting, such as MD/HD-CT with a good tolerability profile. Disclosures No relevant conflicts of interest to declare.

4892 Introduction Mantle cell lymphoma (MCL) is a distinct B cell non Hodgkin lymphoma characterized by CD 5 expression, t (11; 14)(q13; q32) translocation and over-expression of Cyclin D1, and frequently has an aggressive clinical course. There is no standard of care for the treatment of MCL. Current treatment approaches are non curative and pts median survival is 4–6 years. Various studies have reported promising results for a high dose Cytarabine-containing regimen in the treatment of MCL. Fludarabine has also been recognized as effective treatment in pts with MCL, either as a single agent or in combination with other drugs. The addition of Rituximab improves the response to the treatment. The aim of this study is to assess the efficacy and toxicity of a combination of Fludarabine, Aracytine and Rituximab treatment in refractory and relapsed MCL. Methods We retrospectively evaluated 20 pts with refractory or relapsed MCL treated in our institution between February 2007 and February 2010. Median age was 59 yrs (54-77 yrs), 14 pts (70%) were males, 18 pts (90 %) had stage IV, 16 pts (80%) had bone marrow involvement, 16 (80%) presented comorbidities. Eight pts (40%) were in first relapse, 12 (60%) in second relapse. Twelve pts (60%) had a “Mantle Cell Lymphoma International Prognostic Index” (MIPI) score ≥ 7. Therapy included: fludarabine 25 mg/m2/daily intravenously for 3 days, aracytine 500 mg/m2/daily for 3 days and Rituximab 375 mg/m2/daily for 1 day, Dexamethasone 8 mg daily for 3 days, every 28 days for 4 cycles. Results Eight pts (40%) achieved complete response (CR) and 4 pts (20%) a Partial Remission (PR) with an overall response rate (ORR) of 60%. Eight pts (40%) progressed and one of them died of active disease. After a median follow up of 17 months (range 8–36), OS is 70% and PFS is 55%. Toxicity was mainly hematological with grade >=3 neutropenia in 40 (50%) of the 80 cycles performed, grade >=2 anemia in 30 (37%) and grade 4 thrombocytopenia in 24 (30%). In 16 (20%) cycles pts required red blood cells transfusions, in 12 (15%) platelet transfusions. One episode of Herpes Zoster infection was observed. Conclusions This study suggests that the combination of Fludarabine, Aracytine and Rituximab appears to be an effective regimen with a promising response rate and manageable toxicity, for pretreated pts often affected by comorbidities and with poor prognosis. Further studies are needed to assess the efficacy of this combination therapy and to further test the role of this approach in MCL. Disclosures: No relevant conflicts of interest to declare.