ALL-073: Inotuzumab Ozogamicin (IO) and Donor Lymphocyte Infusion (DLI) are a Safe and Promising Combination in Relapsed Acute Lymphoblastic Leukemia (ALL) After Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Abstract

Context Post-HSCT relapse of B-cell ALL is associated with a dismal outcome. IO allows, in the setting of R/R B-ALL patients, high response rates, but with limited duration. Objective To report the outcome of 8 B-ALL adult patients, relapsed after allogeneic HSCT, treated with IO and DLI. Design Retrospective analysis (first patient treated in April 2015, last patient in October 2019). Setting Multicenter (Italian centers). Patients or other participants Five Ph-negative and 3 Ph-positive B-ALL adult patients, with BM disease (6 morphological relapse and 2 MRD-positivity) were treated; 2 patients had additionally extramedullary (EM) disease. Three patients were in salvage 1, 5 patients in salvage ≥ 2; 50% of the patients had previously received Blinatumomab. Median time from transplant to relapse and from relapse to IO was 11 (range 2-21) and 2.5 (range 0-65) months, respectively. Interventions Patients received a median of 3 (range 2-6) IO courses. Four patients received IO and DLI in an alternate schedule and 4 patients sequentially after IO; a median of 3 (range 2-4) DLI at escalating dose was administered (1st dose ranging from 1 × 104/kg CD3+ to 5 × 106/kg CD3+; following doses from 1 × 105 to 5 × 107/kg CD3+). Main outcome measures CR and MRD rate, EM response, DFS, OS, toxicity. MRD was evaluated with BCR-ABL fusion transcript or V(D)J IgH/TCR disease-specific rearrangement on BM. DFS and OS were calculated from start of IO. Toxicity was graded according to CTCAE version. 4.03. Results All patients achieved CR after 1st IO cycle. Six of 8 patients obtained MRD negativity after 2nd IO cycle (4 of 6 patients after 1st cycle). Both PET+ patients achieved PET-negativity. With a median follow-up of 23.5 (range 3-58) months, 6 of 8 (75%) patients are alive. Four of 8 (50%) patients relapsed, of which 2 with CNS localization. Median DFS is 12 months (range 3-58) and median OS is 23.5 (3-58) months. Four out of 8 patients experienced G4 thrombocytopenia. Two patients experienced grade 1 GvHD and no VOD were reported. Conclusions IO and DLI are a safe combination in the post-HSCT setting that may ameliorate the dismal prognosis of this patient subset.