Survival after blinatumomab treatment in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia

Survival after blinatumomab treatment in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. MRD-negative remission, and 5 patients (39%) underwent HSCT. In the 12 patients with primary chemorefractory B-ALL treated with immunotherapy, 11 (92%) achieved minimal residual disease (MRD)-negative remission as assessed by flow cytometry; 10 patients (83%) underwent subsequent hematopoietic stem cell transplant (HSCT). Two patients with B-ALL in MRD-negative remission received blinatumomab due to severe infection and remained in remission after chemotherapy continuation. Conclusions: Blinatumomab and inotuzumab can induce deep remissions in patients with rrALL and facilitate subsequent HSCT or other cellular therapies. Blinatumomab can also serve as Azaperone an effective bridging therapy during severe infection. The optimal timing, choice of Azaperone immunotherapeutic agent(s), and duration of responses require further investigation via larger-scale clinical trials. B-ALL diagnosis, patients were a median age of 9.2 years (0.4C29.2). Seventeen of the 27 (63%) were male, 10 were NCI standard risk (SR; 37%), 17 were NCI high Azaperone risk (HR; 63%), and 21/27 (78%) were CNS 1 at diagnosis (Table 1). Open in a separate window Figure 1. Schema of administered immunotherapy to pediatric patients with B-ALL. Table 1. Demographic characteristics and initial risk status at B-ALL diagnosis. fusion14.3Late medullaryCHOP73.9MCNS 2cSRdeletion9.8Late medullaryCHOP1313.8MCNS 1HRfusion15Early medullaryCHOP143.4FCNS 1HRfusion and deletions5.9Early medullaryCHOP156MCNS 1SRdeletion7Early medullaryCHOP166MCNS 1SRPartial iAMP21 amplification12.5Late medullaryCHOP1714.3MCNS 1HRLow hypodiploidy15.4Early medullaryCHOP1811MCNS 1HRLow hypodiploidy11.8Very early medullaryUCSF218.5FCNS 1SRfusion10.4Early medullaryUCSF231.9MCNS 1HRNone detected6.1Early medullaryUCSF2414.3MCNS 1HRiAMP1 and amplification deletion15.2Early medullaryCHOP253.3MCNS 1SRHypodiploidy12Late medullaryCHOP266.9FCNS 1SRTrisomy 510.2Late medullaryRefractoryUCSF119.4FCNS 1HRHypodiploidy–UCSF211MCNS 1HRNone detected–UCSF318.8MCNS 2HRfusion–UCSF55.3MCNS 1SRHyperdiploidy–CHOP80.4MCNS 2aHRrearrangement–CHOP917MCNS 1HRfusion–UCSF1029.2MCNS 2cHRfusion mutation fusion–CHOP1218.5MCNS 1HRmutation CDKN2A deletion–UCSF1926FCNS 1HRfusion–UCSF2212.8FCNS 1HRNone detected–CHOP2710.4FCNS 1HRfusion–OtherUCSF41.8MCNS 2bSRHyperdiploidy–UCSF200.8FCNS 1HRfusion-Early medullary Open in a separate window *very early = medullary relapse 18 months, early = medullary relapse = 18 months and 36 months, late = medullary relapse 36 months from initial B-ALL diagnosis, – = not applicable. At the time of blinatumomab and/or inotuzumab administration, 13 (48%) were in first or greater relapse, 12 (44%) patients were classified as refractory (MRD 0.01% after two or more induction attempts), and two (7%) patients had B-ALL complicated by an acute infection that precluded administration of standard-of-care cytotoxic chemotherapy (Table 2, Supplemental Table 1). The median number of cycles for each immunotherapy agent was one (range 1C4). Individual clinical courses and outcomes are shown in Figure 2. Representative patients from each of the three disease classifications are presented below as illustrative teaching cases prior to summary data for this case series. Open in a separate window Figure 2. Swimmer plot of patients responses to immunotherapy.The clinical course of each patient is shown over time; each bar represents one patient. Therapeutic agents, disease status, and clinical outcomes are illustrated by symbols shown on the right. Table 2. Treatment and outcome characteristics Azaperone for patients who received blinatumomab and/or inotuzumab. infection. He tolerated blinatumomab well without toxicity, and his marrow remained MRD-negative prior to resumption of post-induction therapy as per AALL0932. He is currently in maintenance and in continued clinical remission at 22 months from diagnosis. Relapsed disease Among the 13 patients with multiply-relapsed disease, the median percent of bone marrow blasts by FC prior to therapy was 51.8% (0.08C98) Azaperone and 21.0% (0.0C97.9) post-therapy. Best response was categorized as MRD-negative CR for 4 patients (31%, 1 following blinatumomab, 3 following inotuzumab), morphologic CR for 1 patient (8%) who received both blinatumomab and inotuzumab, PR for 1 patient (8%) following inotuzumab, SD for 2 patients (15%) after inotuzumab, and PD for 5 patients (39%, 1 following blinatumomab, 2 after inotuzumab, and 2 after both blinatumomab and inotuzumab). Four of the 13 patients (31%) underwent HSCT after inotuzumab (n=3 patients) or blinatumomab (n=1) therapy. Five of the 13 patients also received CD19CART and/or CD22CART following inotuzumab or blinatumomab, four of them Rabbit Polyclonal to SENP6 intended as definitive therapy without planned subsequent HSCT (Table 2, Figure 1). Two of the 5 patients who achieved CR were alive and in continued remission with a median of 21.9 months at the time of.