ANTI-CMV IMMUNOGLOBULINS IN ASSOCIATION WITH ANTI-CMV DRUGS IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES SUBMITTED TO ALLOGENEIC STEM CELL TRANSPLANTATION: A MULTI-CENTRE RETROSPECTIVE EXPERIENCE

P531 ANTI-CMV IMMUNOGLOBULINS IN ASSOCIATION WITH ANTI-CMV DRUGS IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES SUBMITTED TO ALLOGENEIC STEM CELL TRANSPLANTATION: A MULTI-CENTRE RETROSPECTIVE EXPERIENCE Michele Malagola 1 , Benedetta Rambaldi 1 , Jacopo Peccatori 2 , Anna Paola Iori 3 , Raffaella Greco 2 , Elisabetta Xue 2 , Giuseppe Gentile 3 , Luisa Quatrocchi 3 , Giulia De Luca 3 , Enrico Morello 1 , Nicola Polverelli 1 , Alessandro Turra 1 , Federica Cattina 1 , Valeria Cancelli 1 , Robin Foà 3 , Fabio Ciceri 2 , Domenico Russo 1 1 Bone Marrow Transplant Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; 2 Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milano, Italy; 3 'Sapienza' University, Department of Cellular Biotechologies and Hematology, Policlinico Umberto 1, Rome, Italy Background: CMV represents one of the most serious life-threatening complications of allogeneic stem cell transplantaion (allo-SCT). Pre-emptive treatment with anti-CMV drugs is highly effective, but toxicity and repetitive reactivation of CMV represent a major challenge in the clinical practice. The use of anti-CMV specific immunoglobulins (Megalotect) is controversial. Methods: We retrospectively collected data on 294 patients with hematological malignancies submitted to allo-SCT in 3 Italian Bone Marrow Transplant Units between 2016 and 2017. One-hundred and fifteen of the 294 patients (39%) developed at least one CMV reactivation with CMV copies >1000/ml at a median of 35 days (range: 2-120) from transplant. In 19/115 cases (17%), Megalotect was used with the following schedule: 9 patients received 50 UI/Kg weekly, 4 patients 50 U/Kg every 2 weeks, 6 patients 50 UI/Kg every 3 weeks up to CMV viremia negativity. Megalotect was added in high-risk patients, based on: haploidentical allo-SCT (9/19; 47%), steroid therapy for aGVHD (11/19; 58%) and unfavorable CMV serology combination (12/19; 63%; D-/R+ in 11 cases and D-/R- in 1 case). In 12 cases, Megalotect was used as pre-emptive therapy and in 7 cases as prophylaxis. Moreover, a specific anti-CMV drug was used first-line, together with Megalotect, in 12/19 cases: foscarnet (4 cases), valgancyclovir (6 cases), gancyclovir (2 cases). Results: Overall, the treatment was well tolerated, with no reported infusion reactions nor other adverse events. Megalotect was administered for a median of 12 doses (range 5-33) and 2 doses (range 2-9) in patients treated pre-emptively or prophylactically. Focusing on the 12 cases treated with Megalotect pre-emptively, all patients except 1 achieved at least one CMV viremia negativity during tratment. Median time to first negativity was 24 days (range 6-120). In 7/12 cases (58%), a second-line treatment was used. The median interval from subsequent anti-CMV treatment after first negativity was 30 days (range 10-80). In 5/12 patients (42%), maintenance treatment with Megalotect alone was able to control a persistent low-level CMV viremia (< 1000 copies/ml) without any other anti-CMV specific treatment. Focusing on the 7 cases treated with Megalotect as prophylaxis, 1 patient only developed CMV reactivation, treated with gancyclovir with no response. Interestingly, in these 19 high-risk patients CMV disease was observed in 2 cases only (10%): a pneumonitis in 1 case and a colitis in 1 the other. Conclusions: Our preliminary experience with Megalotect suggests that it is safe and well tolerated both in the pre-emptive and prophylaxis setting. We have no conclusive data regarding the efficacy of this treatment in reducing the cumulative dose of anti-CMV specific drugs. Interestingly, when used as pre-emptive therapy, Megalotect was able to maintain low levels of CMV viremia allowing to spare drug toxicity in 5/12 cases (42%). Further prospective randomized trials are warrented to address this specific issue, particulary in patients at high-risk of multiple CMV reactivation and CMV disease.