ALBERT

Description: Background: Fludarabine phosphate (F)-based nonmyeloablative conditioning regimens are associated with reduced transplant-related toxicity and allow transplantation in patients (pts) above 55 y.o. Aims: We prospectively studied the role of ATG to control the development of graft-versus-host-disease (GVHD), accelerate donor engraftment and maintain GVT effects in pts not eligible for classical allogeneic transplant. The subgroup of pts with 60 yo or more was analysed and compared with the younger population. Population: A total of 113 pts were enrolled in the phase II study. Pts with lymphoid malignancies were conditioned with F (30 mg/m²/day for 4 days) plus cyclophosphamide (1g/m²/day for 3 days) or cytarabine (Ara-C, 2g/m²/day) for myeloid malignancies. All pts received cyclosporine (3–5 mg/kg IV, daily) and ATG (10 mg/kg/day for 4 days - [ATG-4, n= 36] or 2 days - [ATG-2, n=67] ). Chimerism analyses were performed on d30, 45, 60 and 90. Results: 29 pts had 60 y.o. or more.Diagnoses were as follows: 9 MM, 5 NHL, 3 CLL, 5 AML, 4 MDS, 2 CML, 1 WM. The median age was 63 (range 60–74) years. The median follow-up was 24 months. Prior to transplantation, 35% of pts were in complete remission. 65% had poor prognostic disease(PR, RR or PD). Engraftment rate was 100% of the evaluable pts. Treatment-related mortality was 48%,much higher than in the younger population (15%) and due primarily to infectious complications. Grade II-IV acute GVHD (aGVHD) at d90 were similar in both populations (35%). Chronic GVHD rates were similar in both groups (40%). At d90, 23 pts were evaluable for T-cell chimerism analysis. Full (〉90%) donor chimerism was achieved in 20/23 pts. Overall survival was higher in patients with good prognostic diseases (60% vs. 48%). No pts developed veno-occlusive disease. Conclusion: These results confirm the feasibility of F-based nonmyeloablative conditioning in elderly population but infectious complications remain a concern compared to younger population.

Description: Chronic lymphocytic leukemia (CLL) occurs in older individuals with a median age at diagnosis of 72 years. In recent years, there has been considerable progress in the frontline therapy of elderly/physically unfit patients with CLL. The German CLL11 trial showed that addition of obinutuzumab to chlorambucil (G-Clb) prolongs progression free survival (PFS) and overall survival (OS) compared to chlorambucil alone or in combination with rituximab. More recently, obinutuzumab together with ibrutinib or venetoclax were shown to be superior to G-Clb with regard to PFS, but there was no advantage in terms of OS. In this retrospective, multinational and multicenter co-operative study the European Research Initiative on CLL (ERIC) and the Israeli CLL Study Group (ICLLSG) evaluated the efficacy of frontline treatment with G-Clb in patients with CLL, in a "real-world" setting. Our analysis excluded CLL patients with documented del(17p) or TP53 mutations since they are no longer treated with chemotherapy. Results: A total of 437 treatment-naïve patients with CLL from 51 medical centers located in 13 countries were included. The median age of this patient population was 75.9 years; 59.7% were men, median CIRS total score was 8 and estimated creatinine clearance 61.1 mL/min. Seventy four patients had Binet stage A (17.2%), 167 (38.8%) stage B and 190 (44.1%) stage C. Results of FISH and IGHV mutational status were available for 332 and 115 patients, respectively. High-risk cytogenetics, del(11q) was documented in 18.7% patients and IGHV-unmutated gene in 64.4%. The vast majority of patients were treated with G-Clb (N=408) and the rest with obinutuzumab monotherapy (G-monotherapy, N=29). The clinical overall response was 86.5%, including clinical complete and partial responses in 41.6% and 45.8% of cases, respectively. The median observation time was 14.1 months (m) and the median PFS of the entire cohort was 27.6m (95% CI, 24.2-31.0). The PFS for G-Clb was significantly better than G-monotherapy (P=0.001; HR=0.38, 95% CI: 0.22-0.67), being the 2-year PFS estimates 61.8% and 52.8%, respectively. The median PFS was significantly shorter for patients with del(11q) (19.2m) compared to those with normal FISH (not reached, P