ALBERT

Description: Backgroung: Anthracyclines-based regimens remain the gold standard for the treatment of Lymphomas, although the associated cardiac toxicity may limit their use, especially in frail and elderly patients. Patients and Methods: From October 2008 to January 2015 we treated 51 newly diagnosed patients B cell with poor-risk non Hodgkin lymphoma and cardiovascular comorbidities using the R-COMP regimen (rituximab, cyclophosphamide, non-pegylated liposome-encapsulated doxorubicin, vincristine and prednisone). Median age was 72 years (range:46-82 yrs ; 62% ≥ 70 years). As for histology, 26/51 (50%) were Diffuse Large B-cell Lymphoma; 10/51 (20%) Follicular Lymphoma; 8/51 (16%)mantle cell lymphoma; 5/51 (10%) Nodal Marginal Zone Lymphoma; 2/51 (4%) other B-cell indolent Lymphoma. IPI and FLIPI prognostic scores were Intermediate to High in the majority (39/51 = 76%) of the patients. Stage III and IV according to Ann-Arbor staging system was present in 40/51 patients (78%). The median age adjusted Charlsons comorbidity index was 6 (range: 3 to 11). Cardiovascular risk factors were considered: hypertension (39/51pts = 76%), a history or recent acute myocardial infarction (9/51 pts = 17%) and Atrial fibrillation (4/51 = 8%). According to National Institute of Aging/National Cancer Institute (NIA/NCI index), a large portion of patients (39%) presented high-impact conditions mainly consisting of ischemic and arrhythmic diseases, under active treatment. Treatment was well tolerated and toxicities were limited grade III/IV cytopenia. RESULTS: Complete remission was achieved in 37/51 (72%) and partial response in 8/51 (15%). The remaining 12% of patients had a progressive disease . As of July 2015, after a median follow up period of 25 months (range 3-79), the OS, RD, EFS, TTF were not reached ( Figure 1, panel A,B,C respectively). In particular, at 5 years from the treatment starting, OS and RD are both 70% and EFS is 54% .Cardiac toxicity was observed in one patients who died for pulmonary edema, while two patients developed arrhythmias. Conclusions: This study confirm the efficacy and tolerability of R-COMP regimen in elderly patients with cardiovascular comorbidities. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Limited stage follicular lymphoma (FL) is usually managed with involved field radiotherapy (IFRT), although different approaches are currently carried out, ranging from watch and wait to combined treatment. RT on involved lymph nodes allows eradication of the disease only in 40-50% of patients. Anti-CD20 monoclonal antibodies (MoAb), widely used in advanced stage FL, are likely to be effective in reducing the relapse risk, although no scientific evidence of their role has been provided. The aim of this multicenter phase II prospective study was to evaluate the role of MRD in identifying patients unlikely to be cured by RT, for whom an immunotherapy-based consolidation could improve outcome. Methods 110 patients with stage I/II FL were enrolled. IFRT was administered to all patients at a dose of 24 Gy. Peripheral blood (PB) and bone marrow (BM) samples were centralized to the Italian FIL (Federazione Italiani Linfomi) MRD Network of EuroMRD-certified laboratories: the presence of a BCL2/IGH rearrangement was investigated at baseline in all patients by nested PCR (NEST) and RQ-PCR (RQ), the latter according to the EuroMRD guidelines. In patients BCL2/IGH+ at baseline by both NEST and RQ in BM and/or PB, MRD was analyzed in both tissues after IFRT and every 6 months over a three-year follow-up period. Patients with positive MRD by both NEST and RQ in BM and/or PB after IFRT or who became positive during the follow-up were treated with 8 weekly doses of the anti-CD20 MoAb ofatumumab. The primary objective of the study was to define the efficacy of immunotherapy in obtaining the disappearance of BCL2/IGH rearranged cells. Results Preliminary data are available for 107 patients, 57 males, 50 females. Median age was 55 years (29-83). 17% had G1 FL, 32% G2, 40% G3A, 11% NOS. The FLIPI score was 0 in 59% of patients, 1 in 35%, 2 in 6%. 69% of patients had inguinal site involvement. Despite a negative BM biopsy, at baseline 30% of patients (n=32) had a BCL2/IGH rearrangement (30 MBR, 1 MBR and mcr, 1 mcr) in the BM and/or PB; the concordance between compartments was 90%, with 10% of negative PB showing a positive BM. No significant differences were observed in relapse probability between patients with or without a molecular marker. All patients were submitted to IFRT and all obtained a clinical response, which was complete in 79 of the 101 evaluated patients (78%) and partial in 22 (22%). MRD evaluation after treatment revealed the persistence of BCL2/IGH rearranged cells in the PB and/or BM in 60% of patients. According to the design of the protocol, MRD-positive patients, either after IFRT (n=18) or in case of conversion to a positive signal during the follow-up (n=7), received 8 weekly administration of ofatumumab. A conversion to MRD negativity, evaluated in 23 treated patients, was obtained in 20 (87% - CI 65.1-97.1). This result was significantly superior to the expected 50%. One death occurred after IFRT, due to ischemic stroke. Adverse events likely correlated to ofatumumab occurred in 7/25 treated patients, consisting of infusion reactions in 5, leading to a permanent interruption of immunotherapy in 3. After a median follow-up of 18 months, all patients who achieved a MRD negativity with ofatumumab underwent a regular molecular follow-up and are still MRD-negative. Overall, clinical relapse or progression were observed in 17 patients: 13 (18%) among the 73 "no marker" patients; 2 relapses (16%) were observed among the 12 MRD-negative patients after IFRT and 2 relapses were observed among the 23 patients treated with the anti-CD20 MoAb (8.7%), 1 having achieved a MRD negativity and 1 not. No significant differences in event-free survival have so far been observed between the three groups. Conclusions The MRD data of this phase II trial for early stage FL indicate that RT alone is often insufficient to eradicate the disease, being capable of inducing a negative MRD only in 40% of evaluable cases, with a long-lasting effect only in half of them. The primary objective of this study - MRD negativity after immunotherapy - was achieved, obtaining the disappearance of BCL2/IGH rearranged cells in the majority of patients treated with ofatumumab. The strategy of an immunotherapy consolidation after IFRT in MRD-positive patients allowed to increase molecular responses. A longer follow-up and further studies on larger patient populations will allow to conclusively define the impact of this MRD-driven strategy also on clinical outcome. Disclosures Pulsoni: Roche: Consultancy, Speakers Bureau; Takeda: Consultancy; Pfizer: Consultancy; Sandoz: Consultancy; Gilead: Speakers Bureau; Merk: Consultancy; Bristol Meyer Squibb: Speakers Bureau. Ferrero:Servier: Speakers Bureau; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Gilead: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Luminari:ROCHE: Other: Role as Advisor ; CELGENE: Other: Role as Advisor & Travel Grant; TAKEDA: Other: Travel Grant; GILEAD: Other: Lecturer . Liberati:Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Celgene: Honoraria, Other: Clinical trial support; Bristol-Myers Squibb: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Janssen: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Roche: Other: Clinical trial support; Novartis: Other: Clinical trial support. Ferreri:Roche: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Kite: Consultancy. Nassi:Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy. Corradini:Roche: Honoraria; Novartis: Honoraria; kite: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Servier: Honoraria; Sanofi: Honoraria; Takeda: Honoraria. Mannina:Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Arcaini:Celgene: Speakers Bureau; Gilead Sciences: Research Funding; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses. Galimberti:Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau. Ladetto:AbbVie: Honoraria; Roche: Honoraria; ADC Therapeutics: Honoraria; Acerta: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; J&J: Honoraria; Celgene: Honoraria. Foà:Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: The anti-CD20 MoAb Ofatumomab is employed to eradicate Minimal Residual Disease in early stage Follicular Lymphoma(FL). The drug is registered for Chronic Lymphocytic Leukemia, not for FL.

Description: INTRODUCTION MCL is an incurable disease and treatment approach should be adapted to patient's characteristics: age, PS, co-morbidities, social conditions, presence of caregiver, etc. In this study we describe the experience of RELLI in real life about old MCL pts followed in Latium region and diagnosed and registered in our database between January 2013 to December 2017. MATHERIALS and METHODS Data were collected in a regional data base. All new diagnosis of lymphoproliferative disease were considered medical history, clinical characteristics and lymphoma related characteristics were registered starting from an existing data base or medical records of single Institutions. RESULTS In the database were registered 91 pts with MCL (70M/21F) older than 65 years with a median age of 74 yrs (range 66-87). At diagnosis 11/91 (12.1%) were in stage I-II and 80/91 (87.9%) in stage III-IV; only 6 (6.6%) pts presented systemic symptoms. High levels of LDH were present in 45.1% of pts, at least one extranodal localization was reported in 4.4% and Ki67 〉 30% in 48.5%. Prognostic score was evaluated at diagnosis: MIPI (LR 46.5%, IR 19.7%, HR 33.8%) and MIPI-c (LR 36.6%, ILR 22.5%, IHR 22.5%, HR 18.4%). Treatment was evaluated according to the age of pts: 65 -70 and 〉70 years; in the first group immuno-chemotherapy (ICT) was: Benda containing regimen 43.5% (R-BAC 17.4%, R-B 26.1%) and CHOP-like regimen 36.1% (R-CHOP21 17.4%, R-COMP21 8.7%). In contrast in older pts the choice of ICT was: Benda containing regimen 64% (R-BAC 14.8%, RB49.2%), and CHOP-like regimen 13.1% (R-CHOP21 8.2%, R-COMP 4.9%).The overall response rate (ORR), progression free-survival (PFS) and overall survival (OS) were calculated from the start of treatment and evaluated in the two groups of pts: ORR was 100% in younger (CR 69.6%, PR 30.4%) and 68.8% in older (CR 50.8%, PR 18%). According to the type of ICT, as expected, pts treated with bendamustine containing regimens (+/- Cytarabine) have better response and longer survival. With a median follow-up of 34.5 months, media OS of the entire population isn't reached and PFS is projected at 50% at 60 months. CONCLUSIONS In the era before new biologic drugs the approach to treatment of MCL was sufficiently homogeneous in the Lazio region. In real life Ky67 was principal factor influencing OS. MIPI and MIPI-c score divided the entire population into two groups at high and low risk. Age not change the OS but only the response rate to treatment (Figure 1). Disclosures Abruzzese: BMS: Consultancy; Incyte: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Di Rocco:Roche: Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Pfizer: Speakers Bureau; Sandoz: Consultancy. Martelli:F. Hoffman-La Roche, Celgene, Janssen, Sandoz, Novartis, Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffman-La Roche, Celgene, Janssen, Sandoz, Novartis, Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria; Servier: Honoraria.