Autologous and Allogeneic Hematopoietic Stem-Cell Transplantation for Patients with Richter's Syndrome: A Large Series from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

Introduction. Chronic lymphocytic leukemia (CLL) has typically an indolent course but can undergo transformation into a more aggressive lymphoma so called Richter's syndrome. While the advent of novel targeted therapies is transforming the management of patients with CLL, these drugs failed to prevent the risk of RS. RS is associated with a very poor outcome and is thus becoming the main obstacle to long term CLL control. Autologous (auto-) and allogeneic (allo-) hematopoietic stem-cell transplantation (-SCT) have been recommended as the treatment of choice in eligible patients with clonally related RS (Rossi Blood 2018) but previous experience is still limited to less than 50 cases. We here aimed to investigate the safety and efficacy of both auto- and allo-SCT for patients with RS in a large cohort in a period overlapping the advent of novel agents. Methods. We report on a retrospective study of consecutive adult patients with RS who underwent auto- or allo-SCT between 2008 and 2018 in EBMT centers. Results. A total of 197 patients (M/F= 133/64) were included in the present study; 125 patients received allo-SCT and 72 auto-SCT. The main difference between these 2 cohorts was the median age at transplant that was lower in the allo- than in the auto-SCT group (median age 57 [18-71] vs 61 [39-74] years, p = 0.006). Regarding the allo-SCT cohort, median time from RS diagnosis to SCT was 10 months [1.1-322.8] and 54.2% had received >2 therapeutic lines for RS. At allo-SCT, 60 (48.4%) were in CR and 53 (42.7%) in PR or SD. Most patients received reduced intensity conditioning (RIC) regimen (n= 90, 72.6%) and peripheral blood (89.6%) as stem cell source. Donors were related (matched, n=40 (33%) or mismatched, n=4 (3%)) or unrelated (matched, n= 76 (61%) and mismatched, n=4 (3%). A total of 41 patients (33.6%) received total body irradiation (TBI). With a median follow-up of 48 months, 2-year OS was 46% (36-55%) and 2-year PFS 38% (28-48%). Two-year cumulative incidence of relapse (CIR) was 31% (22-40%) as was the 2-year NRM (Figure 1). Two-year CIR was significantly reduced in patients with ≤2 therapeutic lines for RS (12% (1-22%) vs 41% (26-55%); p=0.005). Performance status affected 2-y PFS (24% (7-42%) if Karnofsky index <90% vs 43% (31-54%) if ≥90%, p = 0.02) and 2-y CIR (52% (33-71%) if Karnofsky index <90% vs 25% (15-35%) if ≥90%, p = 0.004). Considering death as a competing risk, the day 100 incidence of aGVHD, 2-years limited and extensive cGVHD were 34% (25-43%), 20% (11-28%) and 33% (23-43%). Main causes of death were relapse (30%), GVHD (25%) and infection (30%). Regarding the auto-HSCT cohort, median time from RS diagnosis to HSCT was 7.8 months [2.6-102.7] and 66.7% had received >2 lines for RS. At auto-SCT, 36 (52.2%) were in CR and 36 (37.7%) in PR or SD. With a median follow-up of 18 months, 2-year OS was 69 % (56-82%) and 2-year PFS 47% (33-62%). Two-year cumulative incidence of relapse (CIR) was 46% (32-60%) and 2-year NRM was 7% (0-13%) (Figure 2). CR patients presented better PFS (69% (50-88%) vs 29% (9-50%); p=0.002) and OS (82% (66-97%) vs 56% (35-78%) ; p=0.03). Performance status affected 2-y PFS (25% (2-48%) if Karnofsky index <90% vs 55% (38-73%) if >90%, p = 0.005) and 2-y OS (55% (29-82%) if Karnofsky index <90% vs 75% (60-90%) if >90%, p = 0.04). Disclosures Guièze: Janssen: Honoraria; Gilead: Honoraria; Roche: Honoraria; Abbvie: Honoraria. Byrne:Ariad/Incyte: Honoraria, Speakers Bureau. Finke:Riemser: Honoraria, Other: research support, Speakers Bureau; Neovii: Honoraria, Other: research support, Speakers Bureau; Medac: Honoraria, Other: research support, Speakers Bureau. Chevallier:Incyte: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria; Daiichi Sankyo: Honoraria.