ALBERT

Description: Abstract 3956 Background: Recently in large randomized studies, the addition of Rituximab to standard chemotherapy in the first-line treatment of follicular lymphoma (FL) demonstrated improvements in long-term outcome in FL. Methods: We compared the outcome of 111 naive FL patients (pts) treated at our institution from 1995 to 2009 with a single alkylating agent in combination or not with Rituximab: 58 pts received Chlorambucil plus Rituximab (R-Chl) and 53 pts Chlorambucil and prednisone (Chl+PDN). The 2 schedules included an induction phase, where Chlorambucil was given at 6mg/mq for 6 consecutive weeks in both groups and the Rituximab in 4 weekly administrations. The maintenance phase was longer in the Chl+PDN group: Chlorambucil was administered 6mg/mq daily 14 days each month for a total of 12-months of treatment versus 14 days with monthly-Rituximab for 4 consecutive months in the R-Chl group. Results: The demographic and prognostic factors are reported in Table 1. At the end of treatment the ORR was 98% in the R-Chl pts and 77% in the Chl+PDN group, with a percentage of complete response of 79% and 55% respectively. No significant incidence of adverse events were reported and only one HBsAg positive patient in R-Chl group discontinued the therapy. One case of myelodysplastic syndrome was described in a Chl+PDN relapsed patient. With a median follow up of 34 months, the OS and the EFS in R-Chl pts is 95% and 76% respectively. Otherwise, with a median observation time of 82 months in the Chl+PDN group 73% are alive and only 28% of pts maintained the response. The median time to subsequent therapy (TTST) is 21 and 15 months respectively in the 2 groups. Conclusions: The addition of Rituximab to alkylating in first-line treatment in previously untreated FL pts improves significantly the EFS and prolongs the time to next antilymphoma therapy compared with alkylating alone. Because of its low toxicity profile, our combination with Rituximab and Chlorambucil could be considered a first-line therapy, especially in FL patients not eligible for aggressive chemotherapy regimens. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: In the revised 2017 World Health Organization (WHO) classification of lymphoid neoplasms, high-grade B-cell lymphoma with C-MYC and BCL2 or BCL6 rearrangements is classified as Double-Hit lymphoma (DHL), while the term Triple Hit lymphoma (THL) is employed when the three genes are rearranged (Swerdlow SH, et al 2017). Amplification of C-MYC plus BCL2 and/or BCL6 rearrangement or amplification are defined as "atypical DHL and THL" (Li S., et al 2015). We will here collectively refer to DHL and THL as DHL. Both true and atypical DHL are resistant to conventional chemo-immunotherapy and are associated with poorer outcome. The median survival is shorter than 12 months with standard regimens (Snuderl M, et al 2010). The success of intensified chemo-immunotherapy protocols in Burkitt lymphoma, encouraged many Centres to include these regimens in the treatment armamentarium of DHL. Among these protocols, the B-ALL/NHL 2002 of the GMALL multicenter group is an effective and well tolerated regimen in the treatment of Burkitt's lymphoma (Pollen M, et al 2011). We have adopted the GMALL protocol, as our guideline for the treatment of patients with true or atypical DHL. The preliminary experience with the GMALL protocol in 18 patients is here reported. Methods: We retrospectively evaluated patients with true or atypical DHL treated with the GMALL protocol at the European Institute of Oncology in Milan from 2015 and at the Mauriziano Hospital in Turin from 2012. The diagnosis was confirmed according to 2017 WHO classification and immunohistochemistry analysis and fluorescent in situ hybridization were performed in all patients. Patients were treated following the R-GMALL protocol according to their age group with less intensified doses applied to patients older than 55 years. The program was part of the treatment guidelines developed at each Center for the management of lymphoma patients and a written informed consent was obtained from all patients. Results: Eighteen patients were included in this analysis, 14 were true DH and 3 atypical DH and 1 was Burkitt like lymphoma. Five were transformed lymphomas, 4 after follicular and 1 after marginal zone lymphoma. The median age of the whole group was 64 years (range 43-77years). Eleven patients were male (61%), 15 patients (83%) had Ann-Arbor stage IV and 5 (28%) had bone marrow infiltration. Median lymphoma cells proliferation fraction assessed by Ki-67 IHC was 90% (range 70-100%). Patients received a median of 6 courses (range 2-6) of the GMALL schedule, as inpatient therapy. No patients died of infectious complications during chemotherapy. Twelve patients (67%) were in complete metabolic response (CR) at end of treatment and another patient in complete response by CT scan. Of the 5 refractory patients, four have died (3 for lymphoma progression, one due to infectious complications after salvage splenectomy plus RT), one is still alive, under salvage therapy at 7 months from end of treatment. Among 12 patients who achieved CR, 3 relapsed at 7, 10, 16 months from end of treatment, they are presently alive under salvage treatment. At a median follow up of 21.7 month, the median PFS is 21.4 months while median OS is not reached. The two-year PFS and OS rates are 42% and 66%, respectively (figure 1 A & B). PFS was significantly worse in patients with bone marrow infiltration with median PFS of 7 months while not reached in the rest of patients. The median PFS was approximately 17 months for patients older than 55 years (n=13) and not reached for younger patients, with PFS at 2 years of 75%. There was no correlation with transformation, or Ki-67. Conclusion: This study indicates that intensive treatment with B-ALL/NHL 2002 GMALL protocol is effective and well tolerated in true and atypical DHL patients aged up to 77 years. In this preliminary series, the OS resulted superior to that commonly reported with standard chemo-immunotherapies, with median 17-month OS in older patients while median OS is not reached in younger patients. In fact, the results were particularly promising in patients younger than 55 years probably reflecting the proper dose schedule delivery in younger patients. Based on these preliminary results, we are continuing to use the GMALL protocol as upfront therapy in DH lymphoma patients and we are exploring the possibility of improving the therapeutic efficacy by supplementing the GMALL schedule with one of the novel non-chemotherapeutic drugs. Figure 1 Disclosures Derenzini: TG-THERAPEUTICS: Research Funding. Saglio:Celgene: Consultancy; Jansen: Consultancy; Incyte: Consultancy; Pfizer: Consultancy; BMS: Consultancy; Novartis: Consultancy; Ariad: Consultancy.

Description: Background: haploidentical hematopoietic stem cell transplant (HSCT) with post-transplant cyclophosphamide (Cy) is a procedure for patients with advanced haematological malignancies lacking an HLA identical donor. Even if several groups reported interesting results about allograft in lymphoma, the current clinical practice doesn't include routinely allogeneic stem cell transplantation in patients with suboptimal response to salvage strategies. A prospective study based on the use of peripheral blood stem cells (PBSC) as graft source was launched at European Institute of Oncology in 2010. The aim of this paper is to report the results of haplo-HSCT in patients with relapsed and refractory lymphoma with detectable disease before transplant. Patients and Methods: between June 2010 and May 2018, 64 have been enrolled in the study at our institute; the updated experience of 35 patients affected by high risk lymphomas is reported.Haploidentical HSCT was performed with G-CSF mobilized PBSC. Conditioning regimen was either non-myeloablative (31 patients) (Cy 14.5 mg/kg/die days -6,-5, fludarabine 30 mg/m2/die days -6 to -2, and 200 cGy Total Body Irradiation day -1), or myeloablative (treosulfane 14 mg/m2/die days -6 to -3 and fludarabine 30 mg/m2/die days -6 to -2). GVHD prophylaxis consisted of post-transplant cyclophosphamide (50 mg/kg day +3 and +4) and mycophenolate and tacrolimus as previously described.Among 35 evaluable patients, 28 (80%) performed haplo-HSCT for refractory/relapsed non-Hodgkin lymphoma; the remaining patients included 7 relapsed and refractory Hodgkin lymphoma. Median age was 52 (19-73), disease status included 13 (37%) complete remission (2 CR1, 11 CR≥2), 9 (26%) partial response (PR), 4 (11%) stable disease (SD), 9 (25%) progressive disease (PD). A median of 5.5 x106(range 2.45 -13.4) CD34+ cells/kg was infused, with a median of 2.8x108(range 0.3-5.4) CD3+ cells/kg. Median lines of previous treatment: 3 (0-7). Results: four deaths due to infections have been recorded before engraftment. Among all 64 evaluable patients, median time to absolute neutrophils ≥500/µL was 18 days (range 12-29), and 23 days (range 11-65) to platelets ≥20.000/µL. Incidence of grade I-II acute GVHD was 22%, with grade III of 2%. Mild chronic GvHD was observed in 7/60 evaluable patients (1-year cumulative incidence: 13 %). Mixed donor chimerism was achieved in all 60 evaluable patients, with CD3+ chimerism 〉50% at day +28, 〉90% at day + 84. No graft failure has been recorded. CMV reactivation occurred in 77% of lymphoma patients (27/35 subjects at risk), at a median of 35 days (range 5-50) post-HSCT; pre-emptive therapy was effective in all patients. Regarding the lymphoma population, with a median follow-up of 360 days (6-2,460), 19 patients are alive (54%), 18 of them (51% of the whole series) in CR, while the cumulative incidence of relapse is 25%; when disease status at transplant is considered, the incidence of relapse at 2 years is 4% and 54% for chemo-sensitive and chemo-refractory, respectively (see graphic 2 in figure 1). Overall, 16 patients (45%) died; causes of death were PD in 8 patients (50%), infections in 8 (50%) with a cumulative transplant related mortality of 45%. The 3-year PFS and OS for the all lymphoma patients is 58% and 54%, respectively, with 81% and 66% for patients transplanted in CR/PR and 32 % and 31% for those transplanted in SD/PD (p-value 0,001 Log-rank - graphic 1 in figure 1). Conclusions: Haploidentical T-cell replete PBSC transplantation with high-dose post-transplant Cy is a feasible procedure for high-risk haematological malignancies, with an overall toxicity analogous to HSCT with HLA-identical donors. Despite the small study population, haplo-HSCT seems to be an effective strategy even in patients with active lymphoma before transplant. As previously reported, chemosensitive (CR/PR) patients have a better outcome compared to chemo-refractory cases. However, the latter population still may have a benefit from haplo-HSCT as suggested by our data, thus the cellular therapy strategy should not be discouraged in presence of disease (SD/PD). Our future purpose is to enhance the graft versus lymphoma effect with Natural Killer cells infusions. This option will be soon developed at our hospital within a prospective trial. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 1770 Bronchial-associated lymphoid tissue (BALT) lymphoma is a distinct subgroup of low grade B-cell extranodal lymphoma. The limited clinical information available in the literature makes it difficult to understand if such an indolent lymphoma may have a clinical outcome different from that observed in other extranodal marginal zone lymphomas. The aim of this study is to collect and analyze clinical characteristics of patients with primary marginal zone malignant lymphoma of the lung principally focusing on diagnosis, treatment modality, outcome and finally to evaluate biological and molecular features which may correlate with clinical behaviour. We collected clinical information and histological material on 73 patients diagnosed with marginal zone lymphoma of the lung from February 1990 to August 2008. Central pathology reviewed all histopathological material and the diagnosis was confirmed in 64 (88%) patients. The retrospective analysis has been conducted on this subset of patients. The majority of them (58/64) had limited disease at diagnosis with a good performance status (0-1) and low prognostic index (IPI 0–2). FISH analysis showed a rearrangement on 18q21 in 12 of cases. Median time from diagnosis to any treatment was 30 days (range 0–773). Twenty patients received only local treatment including definitive surgery or radiotherapy. 52 patients needed additional systemic treatment because of advanced stage or incomplete surgical resection. Most of them (26) received an alkylating containing regimen while only 10 patients were treated with an anthracycline containing regimen and 16/52 received monoclonal antibody in combination with chemotherapy. With a median follow up of 54 months, 17/64 patients (27%) relapsed. The median time to relapse was 28 months (range 1–82). No difference in terms of PFS or OS was observed among patients receiving systemic anthracycline or alkylating containing regimens. No significant correlation with MALT 1 aberrations was found. Clinical results observed in such retrospective study seem to suggest as surgery clearly benefits patients with localized disease. Chemotherapy can be reserved for early aggressive relapse. Systemic treatment could be recommended for patients with advanced stage or with incomplete response after the surgical procedure: when chemotherapy must be considered, alkylating containing regimens seem the best option. Considering data of a “pre-rituximab era”, the role of monoclonal antibodies still needs to be clarified and ongoing trials from IELSG could be helpful on this topic. Disclosures: No relevant conflicts of interest to declare.

Description: Haploidentical bone marrow transplantation using non-myeloablative conditioning and high-dose, post-transplant cyclophosphamide (Cy) has been shown to be a feasible approach for patients lacking an HLA identical donor with acceptable rates of acute and chronic Graft-versus-Host-Disease (GVHD); in the attempt to reduce the associated risk of graft failure and relapse incidence we decided to apply the same conditioning regimen using unmanipulated mobilized peripheral blood stem cells (PBSC). From June 2010 to December 2014, 31 consecutive patients affected by high-risk hematological malignancies, median age 51 years (range 19-70) (3 Acute Myeloid Leukemia, 6 Acute Lymphoblastic Leukemia, 9 Non-Hodgkin Lymphoma, 5 Multiple Myeloma, 2 Myelodysplastic Syndrome, 6 Hodgkin Lymphoma), with no available HLA identical donor (neither related or unrelated) underwent peripheral stem cell transplant from a haploidentical family donor. Disease status at transplant was the following: 13 complete remission (5 patients in 1°CR, 6 patients in 2°CR, 2 patients in 3°CR), 9 partial response (PR), 1 stable disease (SD), 7 progressive disease (PD), and a patient with myelodysplastic syndrome who received the transplant as upfront therapy. Conditioning regimen consisted of cyclophosphamide, fludarabine and TBI followed by infusion of haploidentical PBSC; post-transplant immunosuppression consisted of high-dose Cy on days +3 and +4, tacrolimus and micofenolate mofetile from day +5. A median of 5.7x106 (range 3.8-13.7) CD34+ cells/kg was infused with a median of 2.8x108 (range 0.3-5.4) CD3+ cells/kg. Patients readily engrafted with a median time to absolute neutrophil count ≥500/µL of 17.5 days (range 14-28) in 28/31 patients and a median time to platelet ≥20.000/µL of 21 days (range 11-60) in 27/31 evaluable patients. Three patients died of infection before engraftment, another patient showed myeloid engraftment but never recovered platelet counts and prematurely died of cytomegalovirus (CMV) disease. At a median follow-up of 366 days (16-1682), 16 patients are alive (55%): 13 patients are in CR, the other 3, all affected by Multiple Myeloma, have progressed and are undergoing other treatments, with a cumulative incidence of relapse of 33%. Fifteen patients have died; causes of death included progressive disease in 9 patients (60%) and infections in the remaining 6, with a cumulative transplant related mortality of 18%. CMV reactivation occurred in 15 of 27 patients at risk, at a median time of 34 days (range 22-55) after transplant, resolving with preemptive therapy in 14 patients and causing a fatal infection in 1 heavily pretreated patient. Grade I-II acute GvHD (aGvHD) occurred in 6/28 evaluable patients, with 1-year cumulative incidence of grade I-II aGvHD of 21% and no incidence of grade III-IV GvHD. Mild chronic GvHD (cGvHD) was observed in 3/27 evaluable patients with 1-year cumulative incidence of cGvHD of 11%. Achievement of mixed donor chimerism was rapid: 22/28 evaluable patients showed a CD3+ chimerism 〉50% by day +28. At day + 84, in 22/26 evaluable patients CD3+ cells chimerism was 〉90%, while 4/26 showed still a mixed donor chimerism: withdrawal of immunosuppression increased CD3+ chimerism in one patient to 90% at day +360; one patient developed hemolytic anemia and he is under immunosuppression, still a mixed chimera at day +401 while in CR; the other two died from infection at +251 and +361 never reaching the full donor chimerism. No graft failure was observed. Our data show that haploidentical non-myeloablative peripheral blood hematopoietic cell transplantation with high-dose post-transplant Cy is a feasible for patients lacking an HLA identical donor. The use of unmanipulated PBSC with the infusion of a greater number of CD3+ cells allows a rapid and sustained engraftment, reduces the risk of graft failure, does not appear to increase the risk of GVHD with a low/moderate relapse risk. Although the incidence of major infection was low, CMV reactivation remains a critical issues and further studies are needed to clarify recovery of CMV immunity and to reduce the overall treatment related toxicity. Disclosures No relevant conflicts of interest to declare.

Description: T-cell lymphomas represent a rare and heterogeneous group of non-Hodgkin lymphomas (NHLs) characterized by dismal prognosis. Current first line chemotherapeutic approaches have not significantly changed during the last 20 years, and several efforts have been made for early risk stratification of T-cell NHL patients with unsatisfactory results. Functional imaging with 2-deoxy-2-[fluorine-18]fluoro- D-glucose positron emission tomography scan (FGD-PET) has demonstrated improved outcome stratification and response evaluation in Hodgkin lymphoma and B-cell NHL, in comparison with computed tomography (CT) scan. Most T-cell lymphomas are FDG avid and FDG-PET is routinely used in clinical practice, however limited and conflicting data are available on the value of FDG-PET in response assessment at the end of treatment (FDG-PETend). With the aim of evaluating the prognostic value of FDG-PETend in T-cell lymphomas we performed a retrospective study evaluating all T-cell NHL patients treated at the European Institute of Oncology (IEO, Milan) over the past 20 years. Clinical data of all T-cell NHL patients treated at IEO from 1995 to 2015 were retrospectively collected. The back bone of first line therapy did not significantly change over time, being based on the administration of CHOP/CHOP-like chemotherapy eventually followed by treatment intensification with autologous stem cell transplantation (ASCT). Post first-line therapy FDG-PET scans were visually evaluated according to the criteria of the international Harmonization Project (positive vs negative). Ninety-eight consecutive patients (58 males, 40 females) with complete clinical data were considered in this analysis. FDG-PET was used for response evaluation starting from 2002, but only 18 patients considered in the present analysis were treated before 2002. Median age at diagnosis was 54 years (range 14-82). Fifty-two patients (53.1%) had Peripheral T-cell lymphomas not otherwise specified (PTCL-NOS), 23 (23.5%) had anaplastic large T-cell lymphoma (ALCL), 15 (15.3%) had acute lymphoblastic T-cell lymphoma (LAL-T), 8 (8.1%) had NK/T-cell lymphoma. Ten patients were diagnosed in stage I, 21 in stage II, 17 in stage III, 50 patients in stage IV. Thirty-two patients underwent ASCT during the study period. Median follow-up was 16 months (range 1-182). 42 patients were evaluated with FDG-PET at the end of first line therapy: 25 had negative (60%), and 17 (40%) positive PET scans. In 56 patients response was evaluated with CT scan only, and complete responses or complete responses unconfirmed (CR/CRu) were detected in 29 cases (51%). The 10-year progression free survival (PFS) and overall survival (OS) of the whole patient cohort were 22% and 32% respectively. To determine the prognostic value of FDG-PETend we first assessed the PFS of PET positive vs PET negative patients. Those patients who were PET positive at the end of treatment had a statistically inferior PFS compared to PET negative ones (5-year PFS: 29% vs 47% respectively; p

Description: The aim of this prospective multicenter trial was to evaluate the efficacy of the nucleoside analogue 2-CdA in combination with Rituximab and to identify possible genetic factors that could influence the clinical response of the combination. From December 2003 to November 2006, 29 pretreated/newly diagnosed pts affected by WM were enrolled in the study. Pts characteristics included: sex (M/F) 9/19, median age 64 (range 36–75 yrs), a median IgM level before treatment of 2567mg/dL; 16 pts were newly diagnosed. The combination therapy was Rituximab at standard schedule (375 mg/mq) on day 1 followed by 2-CdA 0.1 mg/kg (sc injection) for 5 consecutive days. Each cycle was administered monthly for a total of 4 cycles. Clinical responses were evaluated two months after the end of treatment, according to Response Criteria from the 3rd International Workshop on WM. Expression analysis of the genes involved in the activity of 2-CdA (deoxycytidine kinase, deoxyguanosine kinase, 5′-nucleotidase, ribonucleotide reductase 1 and 2, human equilibrative nucleotide transporter and hCNT1) was performed on bone marrow cells, at baseline in 22 pts. The therapy was well tolerated, except in three patients who discontinued Rituximab due to cardiac toxicity during the first or second infusion. The treatment was delayed in 3 pts because of haematologic toxicity (G3 neutropenia) and in 2 of them the 2-CdA dose was reduced after 2 cycles. The only non-haematological complications observed were late respiratory infections which occurred in 3 pts. At a median follow-up of 21 (13–41) months we observed 17 (59%) CR/PR, 7 (24%) MR, 1 (3%) SD and 4 (14%) PD/NR. Pharmacogenomic analysis showed a statistically significant lower expression of the hCNT1 gene in pts who failed the treatment and who achieved a MR or SD than in those who achieved a CR or a PR (p=0.014) suggesting a possible relationship between reduced hCNT1 levels and a diminished clinical activity of 2-CdA. No significant difference was detected in the expression of the other genes analyzed. Our results suggest that the combination of 2-CDA and Rituximab is safe and active in WM pts; the use of pharmacogenomic analysis might contribute to a better selection of the patients who are more likely to respond to such a combination treatment.

Description: In CLL/SLL pts the combination of purine analogue and rituximab represents a well known effective therapy. Human concentrative nucleotide transporter (hCNT1) and human equilibrative nucleotide transporter (hENT1) are proteins involved in uptake of nucleoside analogues into the tumour cells. The aim of this study was to investigate R-2CDA as first line therapy and in pre-treated pts with active CLL and SLL, and to identify, by pharmacogenomic approaches, genetic factors that may predict clinical response to such treatment. 45 pts with active CLL (27 pts) or SLL (18 pts) were treated. The median age was 59 years (31–76). Patients received 4 cycles of rituximab 375 mg/m2 on day 1 and 2-CDA 0.1 mg/kg (subcutaneously) on days 2 to 6. The treatment was repeated every 4 weeks. A CT scan of the abdomen was performed at baseline and at the end of treatment in all pts; CT scan before treatment was abnormal in 42 pts. Minimal residual disease was evaluated by 6-colour flow-cytometry and PCR methods. Treatment outcome was evaluated according to NCI-WG updating guidelines: to confirm a CR the marrow should be free of clonal B-CLL cells by flow-cytometry and a CTscan should be negative. At baseline we investigated, on bone marrow for SLL and on peripheral blood for CLL, the expression of human concentrative nucleotide transporter (hCNT1) and human equilibrative nucleotide transporter (hENT1) using ABI PRISM 7000 Real Time RT-PCR platform in 24 pts. 42 pts (26 untreated) were fully evaluable for response.LDH and beta2microglobulins were abnormal in 14% and 30% of pts respectively. The percentage of neoplastic cells in the bone marrow was more than 70% in 17% of pts. The overall response rate was 88% (26% CR and 62% PR), with 21% of untreated pts and 5% of pre-treated pts achieving a CR. Severe neutropenia (grade 4) developed in 7% of pts. 4 pts developed pneumonia, 1 with neutropenia. 1 pt had reactivation of herpes zoster virus and 1 pt experienced febrile neutropenia of unknown origin. The median TTP was 41 months. There was not statistically significant difference in terms of duration of response between untreated and pre-treated pts (TTP: 44 vs 35 months, p=0.1814). Pts achieving a CR had a longer response duration than pts with PR (p=0.0047). Low serum lactate dehydrogenase levels, a lower (〈 70%) neoplastic marrow infiltration at baseline and a normal CT scan at the end of therapy (independent of response) predicted a longer response duration (p=0.0145, p=0.0164 and p=0.008 respectevely). The pharmacogenomic analysis showed a difference (p=0.8345) in terms of hCNT1 expression levels between patients achieving a CR and pts with PR or NR. Pts in CR had higher levels of hCNT1 expression and the increase of 1 unit of the expression level of hCNT1 is associated with a reduced risk of PD by 33%. The refractory pts had lower levels of hCNT1 than non refractory pts but the difference was not statistically significant. There was no statistically significant difference in terms of hCNT1 expression between CLL and SLL pts. The combination of 2-CDA and rituximab induces a high response rate, including CR in pre-treated pts. The treatment is well tolerated with acceptable toxicity also in pts over 70 years. The achievement of a CR is important to obtain durable response. The correlation between the levels of expression of hCNT1 and the response to therapy needs to be confirmed in larger studies.

Description: Here we present the clinical results and the outcomes of 143 consecutive newly-diagnosed follicular lymphoma (FL) patients (pts) treated with 3 different modalities of treatment in our institution from 1994 until 2007. During this period, from 1994 to 2002, 55 pts received Chlorambucil and Prednisone (Chl+PDN), subsequently 31 pts Rituximab with Chlorambucil (R-Chl) and 57 pts a 4-weekly standard-dose of Rituximab alone (R). Chlorambucil was given in an induction phase at 10mg/day for 6 consecutive weeks followed by a longer maintenance phase in the first group: 2-week pulses of 10 mg daily with 2-week intervals for a total of 12-months of treatment versus four 2-week pulses with monthly-Rituximab. In the single agent R group 36 pts received maintenance with at least 4-bimonthly administrations. The 3 groups were comparable for demographic and prognostic factors: median age at diagnosis was 55 yrs, over 60% of pts were in advanced stages and mainly asyptomatic (about 90%) and over 50% of pts in each group were low-risk FLIPI. A third of pts in both Rituximab-based treatment groups had bone marrow involvement and bulky disease. In terms of ORR 78% of pts treated with Chl+PDN, 97% with R-Chl and 72% with R single agent, obtained a clinical response, with a percentage of complete response of 58%, 90% and 47% respectively. No significant incidence of adverse events were reported and none discontinued the therapy because of toxicity. One case of myelodysplatic syndrome was described in a relapsed patient of the Chl-PDN group. With a median follow up of 72, 56 and 27 months in the 3 groups evaluated, the CR rate was maintained in 29%, 74% and 37% of pts respectively with a median duration of response of 36, 40 and 24 months. Rituximab as first-line in FL pts seems safe, feasible and able to induce a high rate of clinical response similar to those achieved with standard chemotherapy alone. On the other hand, the immunochemotherapy seems to confirm its superiority in terms of response rate and duration of response.

Description: Abstract 5030 Treatment for multiple myeloma is dramatically changed over the past 5 years. Thalidomide containing regimen is now widely accepted as standard treatment for multiple myeloma in first line. The mechanism of action and the toxicity profile of Thalidomide, make this drug suitable for combination with chemotherapeutic agents. We report clinical results in terms of efficacy and safety of an antracycline containing regimen [liposomal doxorubicin (Myocet), Dexamethasone and Thalidomide (ThalDoDex)] In multiple myeloma before autologous transplantation. From June 2007 to June 2010, ThalDoDex was delivered to 28 previously untreated multiple myeloma patients. Median age was 59 years (range 42–71); 5 patients were staged IIA and 21 patients staged IIIA and 2 IIIB; 15, 8 and 5 patients were ISS I, II, III respectively. Fifteen patients presented IgG monoclonal immunoglobuline, 6 IgA, 5 patients light chains myeloma, 1 patient plasma cell leukaemia and one other secretory multiple myeloma. Treatment schedule was as follows: Thalidomide 100 mg/day for 14 days then 200mg/day until the end of induction; Dexamethasone 40 mg days 1à4; Liposomal Antracycline (MYOCET) 50 mg/sqm day 1 for 4 cycles at 4 weekly intervals. LMWH 100UI/kg/day was added to all patients for DTV prophylaxis. All patients were considered for a peripheral blood stem cell transplantation program according to age and clinical outcome. Twenty-five patients are evaluable for response. Fifteen patients (60%) achieved a CR (1 pt) or a nCR (5 pts), or a VGPR (9 pts) with an overall response rate of 80% (CR, nCR, VGPR, PR). Six patients developed transient febrile neutropenia which solved with antibiotics. During neutropenia two patients developed pneumonia treated with appropriate antimicrobial therapy. No major haematological toxicity was observed. No neurological toxicity or thrombotic event was reported. Our experience suggests that ThalDoDex is effective and safe as induction phase in newly diagnosed multiple myeloma patients. The clinical results are similar to those reported with other Thalidomide containing regimens. Liposomal doxorubicin in combination with Thalidomide and steroid may induce an important rate of CR and nCR as requested for the best clinical result of subsequent autologous transplant procedure. Our combination regimen avoiding alkylating agents and proteosome inhibitors may deserve the use at eventually subsequent relapse. Disclosures: No relevant conflicts of interest to declare.