Background: Prognosis of r/r B-NHL is detrimental. Potentially curative therapeutic approaches, such as autologous stem cell transplantation and innovative CAR-T cell therapy, require maximum disease control to achieve optimal results. Glofitamab is a new bispecific antibody, with a unique 2:1 molecular configuration resulting in superior potency compared with other CD20xCD3 bispecific antibodies with a 1:1 format. Aims: Based on these encouraging results, we included 5 heavily pretreated patients in the early access program of Glofitamab, available in our country. Methods: We collected the data of 5 consecutive patients with r/r B-NHL, who were treated with Glofitamab in our department during the last 15 months. Results: Three men and 2 women, median age of 57 years (38-62), were resistant to 4 (n = 3) and 5 (n = 2) previous lines of treatment. The underlying lymphoma was Richter’s transformation of CLL after allogeneic transplantation (alloHSCT), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), r/r diffuse large B-cell lymphoma (DLBCL) after CAR-T therapy and gray zone lymphoma (GZL) transformed to DLBCL. The median number of Glofitamab cycles administered was 3 (2-7). All 5 patients responded early to treatment, which became apparent immediately after the first dose of 2.5 mg. The patient with Richter’s syndrome achieved metabolic remission after the 4th cycle and underwent second alloHSCT after the 7th cycle. Unfortunately, he passed away 8 months after alloHSCT due to disseminated atypical mycobacterial infection, remaining however disease free. The patient with tFL also achieved metabolic remission, but the drug was discontinued after the 7th cycle due to COVID-19 infection. He died two months after Glofitamab interruption due to disease progression and CMV encephalitis. The patient with PMBCL, responded partially after Glofitamab and had mediastinal radiotherapy as bridging therapy to CAR-T therapy. As the latter was delayed due to CMV reactivation and CMV enteritis, our patient deceased due to progressive disease. The patient with DLBCL after CAR-T therapy had initial clinical response after two Glofitamab cycles. Due to severe COVID-19, we decided to hold Glofitamab. COVID-19 and disease progression led to his death, a few weeks after COVID-19 diagnosis. Finally, the patient with transformed GZL had Glofitamab administered as bridging therapy prior to CAR-T treatment. After 3 cycles, while she was prepared to proceed to CAR-T therapy, she was diagnosed with invasive aspergillosis. She is currently been treated with antifungal agents, whereas disease is still active. Cytokine release syndrome (CRS) occurred in 3 out of 5 patients. In all cases it was grade 1-2 and manifested at the first administration of the drug, after 4, 32 and 10 hours respectively, from infusion initiation. CRS was managed with antipyretics and steroids, whereas none patient required Intensive Care Unit support. Only one patient required tocilizumab. No Immune effector cell-Associated Neurotoxicity Syndrome (ICANS) was observed. Summary/Conclusion: Glofitamab is effective in treating patients with r/r aggressive B-cell NHL. Efficacy makes it an appropriate bridging tool to autologous, alloHSCT or CAR-T therapy. Nevertheless, relapse remains a challenge for r/r disease. Adverse events, such as CRS, were generally manageable. Given the fact that it was administered to heavily pretreated patients, caution to opportunistic pathogens should be paid. Indeed, toxicity profile may be proven to be more favorable if the agent is being administered earlier in therapeutic algorithms.

Introduction: Mantle Cell Lymphoma (MCL) is an indolent B-cell non Hodgkin Lymphoma (NHL) with a worse outcome compared to other low grade NHL. The prognosis of the disease is dictated by various biologic and clinical factors. Although MCL is chemosensitive in newly diagnosed patients, soon it relapses. A significant improvement of its outcome has been achieved by the administration of Rituximab (R) based regimens and the intensification of first line treatment by high dose Cytarabine and autologous stem cell transplantation. Methods: To reveal the experience of our Centre on the diagnosis, treatment and outcome of this difficult to treat lymphoma, we collected data from 51 consecutive patients, diagnosed at our department between 1999 and 2020. Results: Thirty nine (39) men and 12 women with median age 68 years (range 33-88) were diagnosed with MCL. All but one had typical histology. One patient manifested the blastoid variant. Ki67 was available for 39 biopsy: In 57% specimens Ki67 was >30% and in 43% Ki67 was ≤30%. In 84% of cases the performance status at diagnosis was good (PS 0-1) and only 16% showed PS 2-4. The majority of patients (90%) had advanced stage disease (III-IV). High MIPI score was observed in 59%, intermediate in 18% and low in 22%. Elevated lactate dehydrogenase was observed in 58% of cases. Nineteen patients received R - Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone (R-CHOP), 11 an intensified regimen, 14 patients R -Bendamustin, 5 patients R - Chlorambucil and 2 subjects had no treatment. Response to treatment showed as follow: Complete Response (CR) 52%, Partial Response (PR) 36%, Stable disease (SD) 2% and Progressive Disease (PD) 10%. Among patients who received an intensified treatment, 9 underwent an autologous transplantation. Twenty two patients with responsive disease beneficed of R maintenance. Over a median follow up of 62.8 months (range 0.3 - 262), the median overall survival (OS) was 165 months (range 0.3 - 262). Twenty three out of 44 (52%) patients with responsive disease, relapsed. The median progression free survival (PFS) was 59 months (range 6 - 140). Sixteen out of 23 (69%) patients achieved a 2nd response. The treatments administered were: R-CHOP (6 patients), R-Bendamustin (6 patients), platinum based regimens (3 patients), Ibrutinib (5 patients), corticosteroids (2 patients), R - Chlorambucil (1 patient). The median PFS and OS after the 1st relapse were 26.4 months (range 6.9 - 165) and 27 months (range 0.2 - 233) respectively. Response to 1st line treatment (p 0.0001), lower MIPI score (p 0.001) and intensified regimen (p 0.0004) were correlated with a better survival. Conclusions: Increasing the percentage of 1st complete response by intensifying the 1st line treatment could improve the survival of patients with MCL. Keywords: Indolent non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.