Abstract: BACKGROUND. Several histological subtypes of lymphoma can occur in the same patient. This event may happen sequentially or simultaneously. We describe a case of sequential diffuse large B-cells lymphoma (DLBCL), occurred shortly after therapy and rapidly fatal, after primary mixed cellularity Hodgkin lymphoma subtype (MCHLs). CASE REPORT. A 24-year-old woman was admitted in March 2006 to our Unit with fever, loss of weight and left sovraclavear lymphoadenopathy. On admission, chest radiography and total body computerized tomography (TB-CT) evidenced bulky mediastinal disease, lung involment, pericardial and pleural effusion. Left sovraclavear limphoadenopaty biopsy was performed and histology revealed MCHLs. Clinical stage was IVB with mediastinal bulky disease (Ann-Arbor Classification). Chemotherapy with doxorubicin-bleomycin-vinblastin- dacarbazine (ABVD) was starded. After 2 cycles TB-CT and PET showed reduced involvement of mediastinum and middle lobe of right lung. We decided to continue with further 4 cycles of ABVD chemotherapy. At restaging, TB-CT was negative; yet TB-PET was again positive with further strong reduction of mediastinal captation and absence of pulmonary involvment. Radiotherapy involved field (RT-IF) on mediastinum was started. Treatment was not well tolerated because infectious episodes occurred. After 3 weeks since the end of radiotherapy the patient showed fever and catarrhal cough. In the suspect of the bronchopneumonia, we performed cultural examination of sputum and hemoculture, turned out negative; broad-spectrum antibiotic and antimicotic therapy was started. TB-CT, performed after a month, showed an oval lesion on right lung, mediastinal ipercaptation, right pleural effusion, sub-diaphragmatic lymphoadenopathies, cystic lesions of kidneys. The patient underwent medistinal biopsy with histologic diagnosis of DLBCL, but she died a week later for heart and respiratory failure. Overall survival was only of 12 months. DISCUSSION. Possibility of development in the same patient of various types of lymphomas has been recognized for some time. To explain this occurrence, the term of multiple histology lymphomas (MHL) has been coined. MHLs may be sequential (different lymphomas at different times) or simultaneus (different lymphomas occurring at same time in the same lymphnode or at different sites). This event is mostly observed in non Hodgkin lymphoma (NHL). (Tucci et al, Haematologica 2005). Eventuality of a NHL after a primitive Hodgkin lymphoma (HL) is very rare (less than 1% of cases), with a variable time of insorgence (incidence is higher in the first 2 years from diagnosis of HL). Simultaneous HLs and NHLs are also very rare. All HL subtypes may evolve in a NHL DLBCL is main histology subtype of NHL from primary HL, with frequent extranodal involvement. Prognosis is poorer than primary NHLs. (Rueffer et al, JCO 2001). Our case shows a quick transformation to DLBCL of a MHLs. This event happened 3 weeks about for the end of therapy. Latent period is very short to consider DLBCL like a secondary neoplasm. Most reliable hypothesis is the common B-cellular derivation of HL and B-NHL, such as it has recently been demonstrated (Fraga M et al, Histol Histopathol 2007). CONCLUSION. The transformation of a HL into a NHL is a very rare event. Since HL is probably a B-cell derived lymphoma, the transformation into an aggressive NHL has to be suspected in presence of dubious images and symptoms and a biopsy has to be performed and standard therapy for NHL quickly started.

Abstract: 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 ( 〈 70 vs ≥70 years), sex, previous ASCT, creatinine clearance ( 〈 60 vs ≥60 mL/min), ISS stage (I vs II vs III), time from diagnosis to EloRd start (≥3.5 years vs 〈 3.5 years), status of the disease at EloRd start (biochemical relapse vs symptomatic relapse vs refractory to last therapy) did not significantly impact on the probability of achieving a response. The median time to first response was 1.6 months, while the median time to best response 2.8 months. 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.