The median OS in patients who did not undergo alloHSCT after mAb2 was 203 days (95% CI, 140-not reported) with the corresponding 1-year OS after mAb2 of 26
The median OS in patients who did not undergo alloHSCT after mAb2 was 203 days (95% CI, 140-not reported) with the corresponding 1-year OS after mAb2 of 26.5% (95% CI, 11.2-62.4). status. The median time between mAb1 and mAb2 was 99 days. Twelve (63.2%) of 19 patients who achieved remission after mAb2 underwent alloHSCT. The median time Mouse monoclonal to CD45RA.TB100 reacts with the 220 kDa isoform A of CD45. This is clustered as CD45RA, and is expressed on naive/resting T cells and on medullart thymocytes. In comparison, CD45RO is expressed on memory/activated T cells and cortical thymocytes. CD45RA and CD45RO are useful for discriminating between naive and memory T cells in the study of the immune system from mAb2 to alloHSCT was 37.5 days. Acute graft-versus-host disease and nonrelapse mortality were observed in 58.3% (grade 3 or higher, 25%) and 41.7%, respectively. With a median follow-up of 16.8 months after mAb2, 19 patients (65.5%) relapsed, and 21 patients (72.4%) have died. Overall survival was not different between alloHSCT and non-alloHSCT patients. In conclusion, patients with B-ALL who relapsed after blinatumomab could be successfully rescued by inotuzumab as a bridge to alloHSCT but represent an ultra-high-risk group with poor overall survival. Further studies, including novel consolidation and treatment sequence, may improve outcomes of these patients. Introduction The prognosis of patients with relapsed or refractory (R/R) precursor B-cell acute lymphoblastic leukemia (B-ALL) has historically been dismal.1,2 Allogeneic hematopoietic stem cell transplantation (alloHSCT) has been the major approach used with potential to provide long-term remission for these high-risk patients.3 Historically, however, only a small proportion of patients Eliprodil with R/R B-ALL have eventually undergone alloHSCT, mostly due to inability to attain disease control or because of compromised organ function.2 More recently, monoclonal antibody (mAb)-based treatments targeting CD19 and CD22 have become more widely used modalities for the treatment of patients with R/R B-ALL. Blinatumomab, a CD3/CD19Ctargeted bispecific T-cell engager consisting of 2 linked single-chain Eliprodil variable fragments, and inotuzumab ozogamicin (inotuzumab), an antibodyCdrug conjugate comprising a humanized anti-CD22 mAb linked to a calicheamicin toxin, have shown superior antileukemic activity compared with conventional chemotherapy and have become favored salvage treatment strategies, including as a bridge to alloHSCT, in patients with R/R B-ALL.4-6 The majority Eliprodil of published clinical data of blinatumomab and inotuzumab are from clinical trials that predominantly reported initial responses to either of these agents only, whereas clinical course and outcomes of patients who received both mAbs have not been well described. Limited data are available on whether patients who relapse after blinatumomab or inotuzumab derive any therapeutic benefit to the alternate mAb.7 Moreover, the clinical benefit and safety of alloHSCT after both blinatumomab and inotuzumab in these heavily treated patients are unclear. Given the routine use of blinatumomab and inotuzumab in clinical practice, patients who relapse after or develop resistance to both of these brokers will become increasingly more common. We therefore studied treatment outcomes and toxicities in 29 patients with B-ALL who received both blinatumomab and inotuzumab for relapsed diseases at our institution. We report patient and disease characteristics, patterns of relapse after each mAb with regard to antigen expression, response to the alternate mAb, and survival with and without subsequent alloHSCT. Patients and methods We reviewed the patient charts of 29 patients aged 15 years with R/R B-ALL who had received salvage therapy for morphologic or measurable (minimal) residual disease (MRD) with both blinatumomab and inotuzumab at Memorial Sloan Kettering Cancer Center between January 2012 and December 2019. Baseline characteristics, details of mAb therapy (including the sequence and schedule of mAb), previous alloHSCT, previous chimeric antigen Eliprodil receptor (CAR) T-cell therapy, interim treatments between 2 mAbs, and post-mAb treatments were extracted from the electronic health record of each patient. Blinatumomab and inotuzumab were administered following the standard dosing and schedules as approved by the US Food and Drug Administration. Response, outcome, and treatment-related adverse events after mAb administration were described. The study protocol was reviewed and approved by the Memorial Sloan Kettering Cancer Center Institutional Review Board and conducted in accordance with the Declaration of Helsinki. The cutoff date for data analysis was June 30, 2020. Complete remission (CR) was defined as bone marrow lymphoblasts 5% and absence or resolution of extramedullary leukemic foci, with or without hematopoietic recovery. MRD was assessed in bone marrow aspirate samples by using multiparameter flow cytometry with sensitivity of at least 10?4 of total leukocyte events as described previously.8 Loss or lack of expression of CD19 and CD22 was defined as follows: samples were generally described as negative for expression if 20% of the abnormal cells showed positivity above.