Inotuzumab ozogamicin and donor lymphocyte infusion is a safe and promising combination in relapsed acute lymphoblastic leukemia after allogeneic stem cell …

C Papayannidis, C Sartor, A Dominietto… - Hematological …, 2021 - Wiley Online Library
C Papayannidis, C Sartor, A Dominietto, E Zappone, M Arpinati, G Marconi, G Cristiano…
Hematological Oncology, 2021Wiley Online Library
Despite progresses in the treatment of B‐cell acute lymphoblastic leukemia (B‐ALL), relapse
after allogeneic Stem Cell Transplant (allo‐SCT) frequently occurs, and prognosis is dismal.
1 Inotuzumab Ozogamicin (IO, a calicheamicin‐immunoconjugate anti‐CD22) and
Blinatumomab (a B‐specific T‐cell Engaging (BiTE) antibody) have been approved as
monotherapy for relapsed/refractory (R/R) B‐ALL, showing better outcomes in terms of
overall survival (OS) and complete remission (CR) rates, when compared to standard …
Despite progresses in the treatment of B‐cell acute lymphoblastic leukemia (B‐ALL), relapse after allogeneic Stem Cell Transplant (allo‐SCT) frequently occurs, and prognosis is dismal. 1 Inotuzumab Ozogamicin (IO, a calicheamicin‐immunoconjugate anti‐CD22) and Blinatumomab (a B‐specific T‐cell Engaging (BiTE) antibody) have been approved as monotherapy for relapsed/refractory (R/R) B‐ALL, showing better outcomes in terms of overall survival (OS) and complete remission (CR) rates, when compared to standard chemotherapy. 2, 3 Nevertheless, after the achievement of such a deep response, a further consolidation strategy is required, since efficacy of these strategies is limited overtime, and a “bridge to SCT” option may offer the best long term outcome. 4, 5 Unfortunately, a further allo‐SCT may not always be feasible, due to patients’ frailty, comorbidities, or persistent transplant‐related adverse events. Moreover, results obtained with a second allo‐SCT in ALL are controversial and often unsatisfactory. 6 Therefore, other consolidation approaches are warranted, and the use of donor lymphocyte infusion (DLI) might be an option in this setting, having historically demonstrated a not irrelevant efficacy. 7 Intriguingly, combining antibodies with DLI may represent a valuable opportunity, in order to potentiate the graft versus leukemia (GvL) effect. The rationale to combine Blinatumomab and DLI is supported by the role of T‐cells as effectors for the antibody, which engages “fresh” donor T lymphocytes obtained with DLI. While pivotal but encouraging data have already been published on this regard and clinical trials are underway (NCT 03982992), no data are yet available on the combination of IO followed by DLI. 8, 9 We retrospectively analyzed patients relapsed after allo‐SCT treated with IO followed by escalating doses of DLI at three Italian Hematology Institutions. Patients signed an informed consent form for IO and DLI therapy and, patients alive at the time of data collection, signed an informed consent form for personal data collection.
Response was defined as CR for bone marrow (BM) blasts≤ 5% and no evidence of extramedullary (EM) disease, evaluated with Fluorodeoxyglucose Positron Emission Tomography (FDG‐PET) in PET positive patients pre‐IO therapy. MRD was evaluated with BCR‐ABL fusion transcript Real‐Time Quantitative Reverse Transcription PCR (q‐RT‐PCR), or V (D) J IgH/TCR disease‐
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