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The combination of elotuzumab, lenalidomide, and dexamethasone (EloRd) enhanced the clinical benefit over Rd with a manageable toxicity profile in the ELOQUENT-2 trial, leading to its approval in relapsed/refractory multiple myeloma (RRMM). The present study is a 3-year follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloRd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 36 months (range 6-55), 236 patients experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 18.4 and 34 months, respectively. The updated multivariate analyses showed a significant reduction of PFS and OS benefit magnitude only in cases with ISS stage III. Major adverse events included grade 3/4 neutropenia (18.5%), anemia (15.4%), lymphocytopenia (12.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 33.9% and 18.9%, respectively. No new safety signals with longer follow-up have been observed. Of 319 patients, 245 (76.7%) reached at least a partial remission. A significantly lower response rate was found in patients previously exposed to lenalidomide. In conclusion, our study confirms that EloRd is a safe and effective regimen for RRMM patients, maintaining benefits across multiple unfavorable subgroups. This article is protected by copyright. All rights reserved.

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Popisujeme připad AL amyloidozy spolu s izolovaným postiženim myokardu. Vzhledem k obrazu refrakterniho srdecniho selhani byla u pacienta provedena ortotopicka transplantace srdce. U srdecniho stěpu byla zjistěna významna infiltrace středni vrstvy srdecni stěny. O deset měsiců později byla u pacienta provedena transplantace autolognich kmenových buněk s přiznivým výsledkem. Tento připad dokazuje, že ortotopicka transplantace srdce s naslednou transplantaci autolognich kmenových buněk u vysoce selektovaných pacientů s AL amyloidozou je život zachraňujicim výkonem.

Introduction Elotuzumab (Elo), an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), received marketing approval in Italy for relapsed or refractory multiple myeloma (RRMM), in combination with lenalidomide (R) and dexamethasone (d) (EloRd) in April 2017. Here we report preliminary data of an Italian real-life experience on EloRd as salvage therapy for RRMM patients treated outside of controlled clinical trials. The primary objectives of this study were to assess the toxicity profile and the efficacy of EloRd administered as salvage therapy in a real-world setting. Methods Retrospective data collection received approval from local ethic committee. The cohort included 180 RRMM patients from 28 Italian centers who received at least one cycle of EloRd as salvage treatment between April 2017 and June 2018. Patients were treated with EloRD according to marketing approval as follows: Elo 10 mg/kg i.v. on days 1, 8, 15, and 22 during the first two cycles and then on days 1 and 15 of each following cycle, R 25 mg on days 1 to 21 of each cycle and d at a dose of 40 mg during the week without Elo, and 36 mg on the day of Elo administration. Responsive patients had to reach at least a partial remission (PR). Results Baseline characteristics are shown in Table 1. Median age of the 180 patients was 72 years (range 48-89 years); 53.9% were males (Table 1). The median number of previous therapy regimens was 1 (range 1-7); 69 patients (38.3%) received a previous autologous stem cell transplantation (ASCT). One hundred and ten patients (61.1%) showed a symptomatic relapse, 36 (20%) a biochemical relapse, and 34 cases (18.9%) were refractory to the last therapy, including bortezomib in 12.8% of patients. Forty-four patients (24.4%) had creatinine clearance ≤60 mL/min. Among the 138 cases evaluable for International Scoring System (ISS), 54 (39.1%) had stage I, 56 (40.6%) stage II, and 28 (20.3%) stage III. At last data collection (June 2018), 164 cases were evaluable for response. The median number of courses administered so far was 5 (range 1-18). The overall response rate (ORR) was 78%, with 9 complete remissions (CRs) (5.5%) and 49 very good partial remissions (VGPRs) (35.4%). A significant higher ORR was observed in patients who had received only 1 previous line of therapy than those who had received >1 line (64% vs 37.5%; p=0.004). Age ( After a median follow-up of 6 months (range 1-18 months) 33 patients stopped treatment due to disease progression and 4 due to toxicity (2 cases after 1 cycle for pneumonia, 1 after 1 cycle for dexamethasone-related psychosis, and 1 after 2 cycles for lenalidomide-related severe skin rash). A total of 17 patients died (7 patients from progressive disease; 2 from an infection; 1 from a second neoplasia; 7 from causes unrelated to therapy). Follow-up data regarding PFS and overall survival are not sufficiently mature to be analyzed. Common grade 3 or 4 adverse events were fatigue (18.9%), anemia (17%), neutropenia (16.5%), lymphocytopenia (15.9%), and pneumonia (15.9%). Infusion reactions occurred in 13 patients (7.2%) and were always of grade 1 or 2. Infusion reactions resolved in all patients and no case discontinued treatment. Conclusions Our real world preliminary data confirm that EloRd is an effective and safe regimen for RRMM patients, particularly if used as first salvage regimen, basically resembling results obtained in controlled clinical trials. Table 1. Table 1. Disclosures Galli: Celgene: Honoraria; Janssen: Honoraria; Sigma-Tau: Honoraria; Bristol-Myers Squibb: Honoraria. Giuliani:Janssen Pharmaceutica: Other: Avisory Board, Research Funding; Celgene Italy: Other: Avisory Board, Research Funding; Takeda Pharmaceutical Co: Research Funding. Mangiacavalli:Janssen: Consultancy; Celgene: Consultancy; Cilag: Consultancy. Ballanti:Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria; BMS: Honoraria. Montefusco:Celgene: Other: Advisory Board; Amgen: Other: Advisory Board; Janssen: Other: Advisory Board. Bringhen:Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Amgen: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; Takeda: Consultancy. Zamagni:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Patriarca:Celgene: Other: Advisory Role; Travel, accommodations, expenses; Janssen: Other: Advisory role; Jazz: Other: Travel, accommodations, expenses; Medac: Other: Travel, accommodations, expenses; MSD Italy: Other: Advisory Role. Di Raimondo:Takeda: Honoraria, Research Funding; Celgene: Honoraria. Petrucci:Takeda Oncology; Amgen; Celgene; BMS; Janssen Cilag: Honoraria, Other: Advisory Board. Offidani:Bristol-Myers Squibb: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board.

Background: Survival rates of multiple myeloma (MM) patients (pts) has improved over the past few years, but patients inevitably relapse and become more resistant to subsequent treatments. Carfilzomib and Pomalidomide were both approved for the treatment of relapsed/refractory MM (RRMM). Combinations including a proteasome inhibitor (PI) plus an immunomodulator (IMiD), such as Bortezomib-Lenalidomide-Dexamethasone (VRD) or Carfilzomib-Lenalidomide-Dexamethasone (CRD), showed a very high response rate with an acceptable toxicity. Moreover, in the CHAMPION1 study (Berenson et al Blood 2016), the weekly infusion of Carfilzomib showed to be as effective as the twice schedule. In this phase I/II study we assessed for the first time weekly Carfilzomib plus Pomalidomide and low dose Dexamethasone (wKPd) for the treatment of RRMM. Here we report preliminary results. Methods: the primary objective of the phase I part of the trial was to determine the maximum tolerated dose (MTD) of wKPd combination. The primary objective of the phase II was to determine the rate of partial response (PR). Patients with RRMM, who received 1-3 prior lines of treatments and were refractory to Lenalidomide were eligible. Treatment consisted of 28-day cycles of oral Pomalidomide at fixed dose of 4 mg on days 1-21 (1 week off), oral or intravenous (iv) Dexamethasone 40 mg on days 1,8,15,22 and iv Carfilzomib at escalating doses on days 1,8,15. Escalation started at the dose of 36 mg/m2 (0 level) and used a standard 3+3 schema based on dose-limiting toxicities (DLTs) occurring in cycle 1. Treatment was continued until relapse or intolerance. Results: A total of 57 patients were enrolled in 6 Italian centers. Fifty-two patients could be evaluated for this analysis (5 patients did not complete the first cycle yet). The median age was 62 years with a median time from diagnosis of 4 years. 17/39 (44%) of patients were considered high risk according to cytogenetic abnormalities [at least one among t (4;14) t (14;16) and deletion chromosome 17 (del17) detected by FISH]. In the phase I of the trial 15 patients were enrolled. The first 3 patients at the dose level 0 of Carfilzomib did not experience any DLT. In the next cohort with Carfilzomib 20/45 mg/m2 a G3 hypertension and a sudden death occurred. According to the protocol, 3 more patients were enrolled at dose level 0: 1 patient experienced G3 atrial fibrillation, 2 patients ≥ G3 hypertension. Considering the serious adverse events (SAEs) occurred, the trial was temporary stopped to evaluate the benefit of continuing the study. All the DLTs were cardiologic and occurred in patients with a prior history of cardiac disease. As per protocol, they were evaluated with ECG and echocardiogram before the enrolment and were considered eligible for the study. The safety committee established new procedures for the evaluation of cardiac function of potentially eligible patients, including 24 h continuing pressure monitoring before the enrolment and serial measurement of blood pressure during and after Carfilzomib infusions. Six more patients were enrolled at dose level -1 (Carfilzomib 20/27 mg/m2) and none experienced a DLT. The MTD was established at dose level -1 with Carfilzomib 20/27 mg/m2, Pomalidomide 4 mg and Dexamethasone 40 mg. In the phase II portion of the trial, 42 patients were enrolled. Considering both phase I and II portions of the study, the most frequent drug related, grade ≥ 3 AEs were hematologic (65% of neutropenia and 13% of thrombocytopenia) and cardiologic (17%, mainly hypertension). We recorded only 4% of infection and ≥ G3 peripheral neuropathy. The overall response rate (ORR) of phase I/II portions was 58% (30/52) including 25% (13/52) of ≥ very good partial remission (VGPR). The ORR of high risk patients was 44% (7/16) including 19% (3/16) of ≥ VGPR. With a median follow-up of 10 months, median progression free survival (PFS) was 9.5 months and the median overall survival was not reached. Conclusions: This is the first phase I/II trial that combined weekly Carfilzomib with Pomalidomide and Dexamethasone. This combination was highly effective in RRMM. After a median follow-up of 10 months, wKRd showed a double median PFS in comparison with Pomalidomide-low dose dexamethasone (Sanmiguel et al Lancet Oncology 2013): 9.5 vs 4 months respectively, confirming the efficacy of combining a PI with an IMiD. An updated analysis will be presented at the meeting. Disclosures Bringhen: BMS: Honoraria; Celgene: Honoraria; Janssen-Cilag: Honoraria; Amgen: Other: ADVISORY BOARD; Mundipharma: Other: ADVISORY BOARD; Karyopharm: Other: ADVISORY BOARD. Larocca:Celgene: Honoraria; Janssen-Cilag: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria. Gaidano:Karyopharm: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Morphosys: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau. Oliva:Amgen: Honoraria; Celgene: Honoraria; Takeda: Honoraria. Sonneveld:Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria. Boccadoro:Janssen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Abbivie: Honoraria; Mundipharma: Research Funding; SANOFI: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding.

Background Multidrug resistance (MDR) remains a major obstacle for successful treatment in cancer, in particular in acute leukemia. In acute promyelocytic leukemia (APL), the high sensitivity to anthracyclines appears to be attributable to the low frequency of MDR proteins overexpression at onset even if 30% of patients still relapse and become resistant to therapy. In attempt to explain different blast cell sensitivity, we studied the expression of PGP, MRP1, MRP2, and LRP in 45 cases of APL, comparing onset of disease with relapse. Methods PGP, LRP, and MRP on bone marrow or peripheral blood blast cells were evaluated by flow cytometry using the MRK-16, LRP-56, MRP-m6, and MRP2 antibodies and results expressed by the mean fluorescence index (MFI). The antibody binding capacity (ABC) for each MDR protein was also calculated. Results At diagnosis, only 2 of 45 patients overexpressed PGP and 1 overexpressed LRP. PGP and LRP overexpressing cases significantly grew up during disease progression and at second relapse mean PGP MFI and mean LRP MFI were significantly higher than at onset (P = 0.001 and P = 0.008, respectively). By analyzing ABC, the same trend was more evident because a significant increment of PGP and LRP was observed at second (P = 0.002 and P = 0.002, respectively), but even at first relapse (P = 0.018 and P = 0.002, respectively). No changes were demonstrated in MRP1 and MRP2 expression in any phase of disease considered. Conclusions Our data confirm the low expression at diagnosis of proteins related to development of drug resistance in APL. The evidence of a relative easy induction of PGP and LRP, but not of MRP, can be useful in choosing drugs to employ for consolidation or rescue therapy. © 2004 Wiley-Liss, Inc.

P-glycoprotein (P-gp), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP) expression, and blast cell intracellular daunorubicin accumulation (IDA) were evaluated in 95 previously untreated cases of adult acute lymphoblastic leukaemia (ALL) using flow cytometry. Forty-five out of 95 (47%) patients were P-gp positive (+), 12/66 (18%) were LRP+ and 11/66 (17%) were MRP+. Eighteen out of 66 (28%) patients showed a simultaneous multidrug resistance (MDR)-related protein expression higher than controls for more than one protein, while 24/66 (36%) cases did not overexpress any protein. Twenty-one out of 24 (87%) cases overexpressing at least one MDR-related protein had a defect in accumulating daunorubicin into their blast cells, while only 4/24 (16%) cases who did not overexpress any protein had similar features. The complete remission rates were similar in MDR-positive and -negative (-) patients but relapses within 6 months were more frequent in P-gp+ cases, and therefore the disease-free survival duration was shorter in P-gp+ than in P-gp- patients (P = 0.01). The number of MRP+ and/or LRP+ cases was too small to be able to draw any conclusion on their role in affecting or predicting therapy outcome. In conclusion, P-gp overexpression associated with a defect in daunorubicin accumulation is a frequent feature in adult ALL at onset and seems to be related to poorer therapy outcome and, consequently, a shorter disease-free survival. LRP and MRP overexpression seems to be a rare event and no conclusion can be drawn on its prognostic role.

There are several reports describing acute liver decompensation in chronic carriers of HBsAg after withdrawal of chemotherapy or immunosuppressive therapy; recently the same was also reported for chronic HCV-RNA carriers. We retrospectively evaluated hepatic toxicity in eleven patients (6 carriers of HCV-RNA and 5 of HBsAg) autotransplanted at our Institution between March '92 and June '98. Male/female ratio was 7/4, median age 41 years (26-56). Nine patients (4 HBsAg) were affected by non-Hodgkin's lymphoma, 1 (HCV-RNA) by chronic myelogenous leukaemia and 1 (HBsAg) by breast cancer. In the immediate post-transplant period in only 1 patient (HBsAg carrier and affected by breast cancer) was hepatitis documented (at about 1 month from transplant) with an elevation of transaminase levels (x20-40 n.v.). Neither other complications, nor toxic deaths were observed. During the post-transplant follow-up (median 31 months, range 9-83) no hepatic abnormalities were observed. All patients are alive at 56 months (20-122) from diagnosis. Currently 10/11 patients are in complete remission, while 1 patient, affected by follicular centre lymphoma, is alive with disease 52 months from autologous stem cell transplantation. Our study shows that both conventional therapy and high-dose chemotherapy can be performed safely in chronic hepatitis B and C virus carriers.

Scleroderma may be one of the most severe forms of chronic graft-versus-host disease (GVHD). We retrospectively evaluated its incidence, predictor variables and outcome in 133 patients who survived at least 4 months after allogeneic hematopoietic stem cell transplantation. The 5-year cumulative incidence was 15.5% in patients with chronic GVHD. The generalized form had a progressive course despite immunosuppressive therapy. Eosinophilia, autoimmune markers, and previous skin involvement by chronic GVHD with disorders of pigmentation were significantly associated with an increased probability of developing scleroderma.

Anthracyclines are powerful cytotoxic agents, used as first-line treatment of leukemias and many other tumors, but host-tissue toxicity is their main dose-limiting factor. However, their therapeutic effects depend not only on the toxicity, hence on the dose, but also on drug resistance. Among the mechanisms that can account for cell sensitivity to anthracyclines, there is an overexpression of drug transport proteins, like the transmembrane P-glycoprotein (PGP), the multidrug- resistance-related protein (MRP) and the lung-resistance-related protein (LRP). Attempts to reduce the toxicity of chemotherapeutic agents without affecting their efficacy have been made using liposomal anthracyclines or cytoprotective agents, as Amifostine. The aim of this study was to evaluate and compare the toxic effects of Daunorubicin, in normal or liposomal formulation, used in combination with WR1065, the active metabolite of Amifostine, against normal and tumor cells. In conclusion these data show that the preincubation with WR-1065 does not inhibit the drug toxic effect on blast cells and on tumor cell lines, independently by their multidrug resistance phenotype, but has a cytoprotective effect on stem cells causing a drug cytotoxicity reduction of 10-20%. This advantage is even higher using the liposomal formulation of DNR. Therefore, Amifostine can offer a chance of protecting normal cells from the toxicity of anthracyclines, in normal or liposomal formulation. The combination of liposomal anthracyclines with Amifostine can confer further advantages in management of leukemic patients, especially the elderly where treatment toxicity is a main problem. These patients may be candidates for alternative therapeutic strategies and the combination of DNX and Amifostine is an attractive treatment for these cases where a low nonhematological toxicity is required.

We evaluated the incidence, the risk factors, and the outcome of late-onset noninfectious pulmonary complications (LONIPCs) among 50 patients who underwent allogeneic stem cell transplantation from unrelated donors. Of the 39 patients surviving at least 3 months, 10 (26%) fulfilled the diagnostic criteria of LONIPCs and were further subclassified as having bronchiolitis obliterans (four patients), bronchiolitis obliterans with organizing pneumonia (four patients), and interstitial pneumonia (two patients). Two patients had a durable partial remission after treatment with prednisone and cyclosporine; the remaining eight patients did not respond to treatment and five of them died of respiratory failure. Advanced stage of disease at transplant and chronic extensive graft-versus-host disease (GVHD) were significantly associated with the development of LONIPCs. Pulmonary function test (PFT) results before transplantation were similar in all patients, but patients with LONIPCs had a significant decrease in PFT indexes at the third month after BMT compared with controls. Moreover, the rate of cyclosporine taper during the fourth and fifth months after BMT was significantly more rapid in patients with LONIPCs than in controls, suggesting that the risk of LONIPCs may be influenced by a faster reduction of GVHD prophylaxis.

P-glycoprotein (P-gp), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP) expression, and blast cell intracellular daunorubicin accumulation (IDA) were evaluated in 95 previously untreated cases of adult acute lymphoblastic leukaemia (ALL) using flow cytometry. Forty-five out of 95 (47%) patients were P-gp positive (+), 12/66 (18%) were LRP+ and 11/66 (17%) were MRP+. Eighteen out of 66 (28%) patients showed a simultaneous multidrug resistance (MDR)-related protein expression higher than controls for more than one protein, while 24/66 (36%) cases did not overexpress any protein. Twenty-one out of 24 (87%) cases overexpressing at least one MDR-related protein had a defect in accumulating daunorubicin into their blast cells, while only 4/24 (16%) cases who did not overexpress any protein had similar features. The complete remission rates were similar in MDR-positive and -negative (-) patients but relapses within 6 months were more frequent in P-gp+ cases, and therefore the disease-free survival duration was shorter in P-gp+ than in P-gp- patients (P = 0.01). The number of MRP+ and/or LRP+ cases was too small to be able to draw any conclusion on their role in affecting or predicting therapy outcome. In conclusion, P-gp overexpression associated with a defect in daunorubicin accumulation is a frequent feature in adult ALL at onset and seems to be related to poorer therapy outcome and, consequently, a shorter disease-free survival. LRP and MRP overexpression seems to be a rare event and no conclusion can be drawn on its prognostic role.

In this work three human cell lines with multidrug resistance (MDR) caused by a P-glycoprotein (PGP) overexpression, CEM VLB, HL60 DNR, LOVO DX and two cell lines with MDR associated with a multidrug related protein (MRP) or a lung resistance-related protein (LRP) overexpression named GLC4 ADR and SW1573/2R120 were tested for Amifostine protection against Daunorubicin, Doxorubicin, Idarubicin and Mitoxantrone toxicity. This class of anticancer agents was chosen because they are commonly used in the first line treatments of acute leukemias where a PGP, an LRP or an MRP overexpression often occurs even at onset. A 7-day incubation with escalating doses of anticancer agents with or without a 15 minute preincubation in Amifostine or its active metabolite WR-1065 were used. In conclusion, in none of the MDR positive and negative cell lines did Amifostine modify the toxicity of the anticancer drugs. The observation that even the WR-1065 metabolite gave no protection against Anthracyclines toxicity strengthened the data and provided confirmation for the further in vivo testing of the safety and efficacy of Amifostine in leukemias.

The outcome of a series of adult patients, affected by primary systemic CD30-positive anaplastic large cell lymphoma (ALCL), treated with a sequential intensive therapeutic program, has been analyzed and all data available in the literature have been reviewed. Forty consecutive, unselected patients with ALCL were treated with the F-MACHOP regimen, followed by radiotherapy (RT) for residual mediastinal disease (15 cases) and by autologous stem cell transplantation (ASCT) conditioned with BAVC (29 cases). Eighty-nine percent (32/36) of the patients younger than 60 years were eligible for completing the sequential treatment. Since then, 3 patients in CR refused ASCT, 1 was excluded for cardiac toxicity and 3 progressed and died of disease. Thus, 29 have been so far submitted to the transplant procedure. CR and PR rates were 40% and 45% respectively after CHT; 52.5% and 35% after RT; 80% and 5% after ASCT, with 78% of patients transplanted in PR convertin to a CR. Actuarial overall survival is 85% at 48.5 months (93% at 66 months for the 29 transplanted patients) and disease free survival is 100% at 54 and 64 months respectively, with no relapses observed among patients who reached a CR. Considering our data and those of the literature, it can be concluded that although the role of ASCT in the therapy of ALCL must not be considered as definitive, its efficacy in converting PR into CR and in preventing relapses, suggests that a randomized trial comparing CHT alone vs CHT+ASCT should be undertaken.

Positron emission tomography (PET) integrated with computed tomography (PET/CT) has been reported to be useful for screening myelomatous lesions at diagnosis in patients with multiple myeloma (MM) and for monitoring response to autologous stem cell transplantation (auto-SCT). The aim of the study was to evaluate the prognostic significance of PET/CT in MM patients who received allogeneic stem cell transplantation (allo-SCT). Patients who underwent upfront auto-SCT followed by allo-SCT, either as consolidation or salvage treatment, were studied with PET/CT before and/or within 6 months after allo-SCT. The number, the maximum standard uptake value (SUV), and the location (medullary or extramedullary) of focal lesions (FLs) were recorded and investigated as predictors of progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analyses. Fifty-four patients had a PET/CT scan before allo-SCT. Of these, 22 patients (41%) had a negative PET/CT scan, 11 patients (20%) showed 1 to 3 FLs, and 21 patients (39%) had either a diffuse bone marrow involvement or more than 3 FLs. SUV was >4.2 in 21 patients (39%) and extramedullary disease (EMD) was present in 6 patients (11%). Multivariate analysis of prognostic factors before allo-SCT showed that persistence of EMD at transplantation was an independent predictor of poor PFS, whereas OS was negatively influenced by unrelated donor and SUV > 4.2. Fifty-nine patients had a PET/CT scan within 6 months after allo-SCT. Multivariate analysis of post-treatment variables showed that persistence of EMD and failure to obtain complete response or very good partial response after allo-SCT were strongly associated with shorter PFS and OS. Of the 46 patients with evaluable PET/CT scans both before and 6 months after allo-SCT, the 23 patients who maintained or reached a PET complete remission showed a significantly prolonged PFS and OS compared with the 23 patients with persistence of any PET positivity (2-year PFS: 51% versus 25%, P = .03; 2-year OS: 81% versus 47%, P = .001). This study indicates that PET/CT imaging before and after allo-SCT is significantly associated with the outcome, suggesting the utility of this technique for MM staging before allo-SCT and for response monitoring after the transplantation.

Background High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). The introduction of novel agents challenged the role of ASCT at diagnosis. We conducted a multicenter 2X2 randomized trial comparing conventional chemotherapy plus lenalidomide with ASCT followed by maintenance with lenalidomide-prednisone (RP) or lenalidomide (R) alone in newly diagnosed young MM (NDMM) patients. Methods Eligible patients with NDMM ≤ 65 years were enrolled. All patients received Rd induction (four 28-day cycles of lenalidomide 25 mg day 1–21 and low-dose dexamethasone 40 mg day 1,8,15,22) followed by stem cell mobilization. Patients were randomized to receive consolidation with CRD [six 28-day cycles of cyclophosphamide (300 mg/m2 day 1,8,15), dexamethasone (40 mg days 1,8,15,22) and lenalidomide (25 mg days 1–21)] or MEL200-ASCT (melphalan 200 mg/m2 with stem-cell support). Patients were randomly assigned to receive subsequent maintenance with RP (28-day cycles of lenalidomide 25 mg days 1–21 plus prednisone 50 mg every other day) or R alone (28-day cycles of lenalidomide 25 mg days 1–21). Primary study endpoint was progression-free survival (PFS); secondary endpoints included safety, responses and overall survival (OS). Data cut off was May 30th, 2013. Results Three-hundred and eighty-nine patients were enrolled in the trial. Patient characteristics were well balanced between CRD (n=194) and MEL200-ASCT (n=195), and between R (n=195) and RP (n=194) arms. Median follow-up was 31 months. In the intent to treat (ITT) analysis, the median PFS was not reached with MEL200-ASCT and 28 months with CRD (the respective 3-year PFS was 60% vs. 38%, HR=0.62, 95%CI: 0.49-0.85, P=0.003). Median time from enrolment to maintenance was 14 months. In the population of patients eligible for maintenance, 2-year PFS from the start of maintenance was 73% for RP and 56% for R patients (HR= 0.57, 95%CI: 0.34-0.93; P=0.03). In the subgroup of patients who received MEL200-ASCT, 2-year PFS from the start of maintenance was 83% for patients who received RP and 64% for those who received R alone (HR=0.36 95%CI: 0.15-0.87, P=0.02). In the subgroup of patients who received CRD, 2-year PFS from the start of maintenance was 64% for patients who received RP and 47% for those who received R alone (HR=0.75, 95%CI: 0.40-1.39, P=0.36). At present, no differences in OS were noticed between patients randomised to received CRD or MEL200-ASCT, and between patients who received RP or R maintenance. As expected, the rates of grade 3-4 hematologic (85% vs. 26%, P Conclusions MEL200-ASCT significantly prolonged PFS in comparison with CRD. At present no difference in OS was reported, this may be due to the low number of events and to the length of follow-up. The increase in toxicity with MEL200-ASCT did not adversely impact on efficacy. The addition of prednisone to lenalidomide maintenance significantly reduced the risk of progression in comparison with lenalidomide alone, without increasing the toxicity. Updated data with longer follow-up will be presented at the meeting. Disclosures: Palumbo: Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria. Gay:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Spencer:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Larocca:Celgene: Honoraria. Caravita:Celgene: Honoraria, Research Funding. Petrucci:Celgene: Honoraria. Hajek:Celgene: Honoraria; Celgene: Consultancy. Boccadoro:Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

The aim of the study was to retrospectively evaluate the outcome of patients with aggressive non-Hodgkin's lymphoma (NHL), undergoing autologous stem cell transplantation (ASCT) in first complete (CR) or partial (PR) remission, according to the age-adjusted International Prognostic Index (IPI). Fifty-two consecutive patients, aged less than 60 years, with intermediate- or high-grade NHL, and at least one of the following adverse risk factors: bulky disease, B symptoms or Ann Arbor stage III-IV, and at least a PR after CHT (and radiotherapy (RT) on residual mediastinal mass when required), underwent ASCT conditioned with BAVC. Sixty-five percent (33/52) of the patients achieved CR after CHT; 69% (36/52) after CHT + RT; 90% (47/52) after CHT +/- RT + ASCT. One death during conditioning and three major toxic events after ASCT were recorded. Overall survival (OS) is 98% at 37 months (16-88); disease-free survival (DFS) is 100% at 27 months (7-82). Comparing the observed results with those expected if patients were treated only with CHT, the sequential treatment including ASCT conferred an advantage in terms of CR rate of 14, 23 and 54%, respectively, in the low-intermediate (LI), high-intermediate (HI) and high (H)-risk groups, respectively. The 2-year OS advantage is 10, 21, 31 and 63%, respectively, and the 2-year DFS advantage is 12, 26, 38 and 39%, respectively. Even more striking is the 5-year projected advantage in the number of patients alive without disease, even when considering only the low (L) (P < 0.0001) and the LI (P < 0.0001) risk groups. For patients in the higher (HI + H) risk groups, ASCT should be included in the initial plan of treatment as consolidation of first CR or PR, but the differences seen in this study suggest a formal comparison in a randomized study also for patients in the LI risk group.