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Introduction In October 2021, brexucabtagene autoleucel (brexu-cel) received U.S. FDA approval as the first CAR T-cell therapy for adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) based on the 55-patient ZUMA-3 Phase II study. We subsequently established ROCCA and now report on the largest cohort of patients treated with commercial brexu-cel for r/r B-ALL to date. Methods Adults (18+) with r/r B-ALL infused with commercial brexu-cel across 25 U.S. institutions were included. ASTCT consensus criteria were used to score CRS and ICANS. Methodologies for assessing MRD (minimal threshold of 10 -4) included flow cytometry, NGS, or qPCR depending on institution practice. Duration of remission (DOR) was calculated from time of complete response (CR); progression-free survival (PFS) and overall survival (OS) were calculated from day of brexu-cel infusion and were not censored for hematopoietic cell transplant (HCT) or maintenance. All living patients were censored at the time of last follow-up prior to data lock, which occurred on June 30, 2023. Results Among 152 infused, the median age was 46 (range, 18-81), 57% were male, and 34% were Hispanic. Most (67%) had Ph- ALL, were heavily pre-treated (median 4 prior lines), and entered apheresis with high disease burden (57%). At time of apheresis, 23% of patients only had MRD+ disease and 15% were in complete molecular remission. While 82% developed CRS, the majority was grade 1-2, with 9% of the overall cohort experiencing grade 3-4 CRS. In contrast, 55% developed ICANS, with 32% of the entire cohort experiencing grade 3-4 ICANS. Eight patients (5%) died of toxicity/infection prior to D+28 response assessment. Among 133 patients with response assessment, 120 (90%) achieved morphologic CR, of whom 82% were MRD-, 15% were MRD+, and 3% MRD unknown. The median follow-up for survivors was 8.4 months; 45 patients have relapsed and 42 patients died. Median DOR was not reached. Median PFS and OS were 8.6 months and 15.6 months, respectively. Estimated PFS and OS of the entire cohort at 6-months were 61% (95% CI, 52-68) and 81% (95% CI, 73-87) and at 12-months were 47% (95% CI, 37-56) and 63% (95% CI, 53-72), respectively. We found no association between pre-CAR disease burden and post-CAR PFS/OS. However, patients with MRD- response to CAR had superior PFS relative to patients with MRD+ CR (median 14 months vs. 5 months, P=0.002). Forty-four patients received post-CAR consolidation/maintenance therapy while in CR: 25 allogeneic HCT, 15 TKI, 2 POMP, and 3 other/unknown. To examine the effect of consolidation/maintenance following brexu-cel, we performed a landmark analysis of PFS limited to patients alive and in CR at 2-months post-CAR infusion (N=113) and suggests superior PFS in patients receiving either HCT or other forms maintenance, relative to those receiving no further therapy following brexu-cel ( P=0.055). We then investigated post-CAR MRD-response in combination with receipt of post-CAR consolidation/maintenance and found that even among patients achieving MRD-negative response, post-CAR consolidation/maintenance led to superior PFS (Figure 1). Conclusions Among 152 adults treated with commercial brexu-cel for r/r B-ALL across 25 U.S. institutions, we found very high response rates (CR/CRi: 90%; 82% MRD-) consistent with the Zuma-3 data. While rates of severe CRS are low, grade 3-4 ICANS was observed in 32% of patients and warrants further investigation We demonstrate the prognostic impact of achieving an MRD-negative CR and an emerging role for consolidation/maintenance therapies to enhance the durability of response following brexu-cel in adults r/r B-ALL.

Background Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR-T) cell therapy that recently received U.S. FDA approval as the first CAR-T cell therapy for adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Social determinants of health (SDoH) are shown to significantly influence outcomes in B-ALL. However, how SDoH relate to and affect outcomes in patients with B-ALL receiving CAR-T therapy has not been well established. We studied the impact of SDoH on outcomes of adults with B-ALL receiving brexu-cel as part of the Real-world Outcomes Collaborative of CAR-T in Adult ALL (ROCCA). Methods This retrospective multicenter analysis spanning 25 U.S centers included adults (≥18 years) with r/r B-ALL treated with commercial brexu-cel between 2021-2023. Progression-free survival (PFS) and overall survival (OS) were calculated from the day of brexu-cel infusion and were not censored for hematopoietic cell transplant (HCT) or maintenance. Univariate and multivariate Cox proportional hazards models were used to evaluate the association of age, sex, pre-apheresis disease burden, and SDoH (referral source, insurance, distance from home to CAR-T site, marital status, and the social deprivation index) with progression-free survival (PFS) and overall survival (OS). The social deprivation index (SDI), a composite measure (including income, education, employment, housing, household characteristics, and transportation) used to quantify socio-economic variation in health outcomes, with higher SDI indicating greater social disadvantage, was estimated at the zip code level. (Butler et al., 2013) Results Of the 152 patients who received brexu-cel (Table 1), 57% were male. 51% identified as non-Hispanic White, with the remainder identifying as Hispanic (34%), Asian/Pacific Islander (7%), Black (6%), American Indian/Alaskan Native (1%), or mixed race (1%). A majority (46%) were referred for brexu-cel from private/community-based practices and 62% lived within 50 miles of the CAR-T center (36% lived >50 miles and 2% were unknown). Health insurance coverage included primarily public (49%) and private (42%); no patients were uninsured. High SDI (76-100% percentile) was present in 26%, while 14% had a low SDI (0-25 th percentile). In unadjusted analyses, there was no difference in PFS or OS between patients with high versus low SDI; closer distance to the CAR-T site (<50 miles versus >50 miles)) was associated with worse OS (HR 1.96; 95% CI 1.00, 3.84; p=0.05). Multivariate analysis (Table 2) revealed that male sex was associated with inferior PFS (HR 1.98; 95% CI 1.02, 3.85; p=0.04) and OS (HR 2.52; 95% CI 1.09, 5.84; p=0.03). There was no difference in PFS (HR 0.95, 95% CI 0.48-1.88, p=0.88) or OS (HR 0.80; 95% CI 0.33,1.92; p=0.62) when comparing Hispanic and non-Hispanic White patients. Additionally, there was no difference in PFS or OS based on any SDoH, including insurance type, marital status, referral source, caregiver type, and distance to transplant center. Conclusions In patients receiving brexu-cel, survival outcomes appear independent of SDoH. Contrary to previous reports suggesting inferior outcomes for Hispanic patients with B-ALL after receiving traditional systemic therapies, we observed comparable outcomes to non-Hispanic patients treated with brexu-cel. Distance from the CAR-T site and referrals from the community did not affect outcomes. Additionally, those with higher SDI had similar outcomes to those with a lower SDI, although this analysis was limited by sample size and the selection bias that exists in being referred for brexu-cel in the first place. The relatively lower logistical burden of CAR-T compared to allogeneic stem cell transplant or non-fixed duration systemic therapies may have mitigated the impact of SDoH on outcomes. These real-world data suggest that continuing to improve access to and treatment with brexu-cel may improve overall outcomes for disadvantaged populations with r/r B-ALL.

Background: Ph-like ALL is a high-risk subset of B-lineage ALL that responds poorly to standard chemotherapy regimens. While allogeneic hematopoietic cell transplantation (HCT) is routinely recommended for patients with Ph-like ALL, large multicenter data addressing its role is limited. Here, we conducted a multicenter study to evaluate the role of HCT in adolescent and young adult (AYA) and adult patients (pts) with Ph-like ALL and compare their outcomes to pts with Ph-pos and Ph-neg (non-Ph-like) ALL. Methods: The study included pts (age ≥18) with B-lineage ALL who received HCT in first complete remission (CR1) at 3 academic centers (MD Anderson Cancer Center, City of Hope and Mayo Clinic) between 2006 and 2021. Pts were divided into 3 main subgroups: Ph-like, Ph-pos and Ph-neg ALL. Ph-like ALL cases were identified using cumulative data obtained by targeted RNA sequencing, conventional cytogenetics, FISH studies, whole genome chromosomal microarray and flow cytometry. Measurable residual disease (MRD) prior to HCT was measured using flow cytometry with a sensitivity of 0.01% for Ph-neg and Ph-like ALL, and with a PCR assay for BCR::ABL1 for Ph-pos ALL. MRD-negativity was defined as <0.01%. Predictors of relapse were evaluated in univariate and multivariate analysis using Fine-Gray sub-distribution hazard models considering non-relapse mortality (NRM) as a competing risk. Results: 673 patients were identified, 83 (12.3%) had Ph-like ALL, of which 73% had CRLF2-alterations. The remaining patients were classified either as Ph-pos (N=271, 40.3%) or Ph-neg ALL (N=319, 47.4%). Patients with Ph-like ALL were younger (median age 40 years vs 48 and 46 years for Ph-pos and Ph-neg ALL, respectively, p=0.01), more likely to be of Hispanic ethnicity (69% vs 32% and 48% for Ph-pos and Ph-neg ALL respectively, p<0.001). Patients with Ph-like ALL were also more likely to have induction failure (24% vs 2% and 11% for Ph-pos and Ph-neg ALL, respectively, p=0.001). A summary of pts characteristics for each subgroup can be found in Table 1. The median follow-up was 30, 52 and 48 months for patients with Ph-like, Ph-pos and Ph-neg ALL, respectively. In univariate analysis, 3-yr OS and PFS did not differ significantly (66% and 59% vs 59% and 54%, p=0.1) between patients with Ph-like and Ph-neg ALL, respectively. Similarly, the cumulative incidence of relapse was comparable between patients with Ph-like and Ph-neg ALL (22% vs 20%, respectively, p=0.7). In contrast, the 3-yr OS (75%, p<0.001) and PFS (70%, p=0.001) were significantly higher and relapse rate significantly lower (12%, p=0.003) in pts with Ph-pos ALL compared with Ph-like or Ph-neg ALL (Figure 1). The inferior survival in patients with Ph-like and Ph-neg ALL was likely attributable to higher relapse rates (22% and 20% vs 12%, respectively, p=0.003) compared to Ph-pos ALL. Finally, the 3-yr NRM rate in patients with Ph-like ALL was comparable (20% vs 18% and 23%, respectively, p>0.1) to Ph-pos and Ph-neg ALL. We confirmed that the relapse rate in patients with Ph-like ALL was comparable to the rate in pts with Ph-neg ALL (HR=1.02, 95% CI 0.6-1.8, p=0.9) on multivariate analysis (MVA). Ph-pos ALL was associated with a significantly lower relapse rate compared with Ph-neg ALL (HR=0.4, 95% CI 0.3-0.7, p<0.001). MRD positivity prior to allo-HCT was the only additional significant predictor for relapse on MVA (HR=2.9, 95% CI 1.8-4.7, p<0.001). Conclusions: HCT appears to overcome the poor prognosis of patients with Ph-like ALL. Despite higher induction failure rates, patients with Ph-like ALL undergoing HCT in CR1 had similar outcomes to other Ph-neg ALL subsets. The impact of effective salvage therapy leading to MRD-negativity in CR1 in this group is under investigation and will be reported. Further studies are needed to assess the impact of different Ph-like alterations on HCT outcomes. Outcomes for patients with Ph-pos ALL are significantly better than other groups, likely due to the use of TKIs pre- and post-HCT.

Introduction: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for adults with relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a CD19-directed bispecific T-cell engager that is also approved for r/r B-ALL, and often used as early salvage therapy. Data in the pediatric/AYA population suggest that patients who did not respond to blinatumomab may have inferior outcomes to CD19-directed CAR-T products compared to those who have achieved a response to blinatumomab or were blinatumomab-naïve (Myers et al. J Clin Oncol 2022). In this study, we evaluate the response to blinatumomab and subsequent response to brexu-cel in adults with r/r B-ALL. Methods: Retrospective data were collected from 25 centers across the U.S. as part of the real-world outcomes collaborative study of CAR-T in B-ALL (ROCCA). Consecutive patients treated with brexu-cel from 2021 to 2023 were categorized by blinatumomab exposure status. Those exposed were separated into “blinatumomab responders” (B-R), defined as patients achieving a CR/CRi in response to any number of cycles of blinatumomab, and “non-responders” (B-NR). Each cohort was compared for outcomes of interest. The primary outcome was CR/CRi rate at day 28 following brexu-cel administration. Secondary outcomes were duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Survival outcomes were calculated from day of brexu-cel infusion and were not censored for allogeneic hematopoietic cell transplantation or maintenance therapy. All living patients were censored at data cutoff on June 30, 2023. Survival comparisons were made by log rank test. Results: Among 152 patients who received brexu-cel, the median follow-up time was 8.4 months. Eighty-eight (57%) of 152 r/r B-ALL brexu-cel recipients had received blinatumomab prior to apheresis. The median number of pre-apheresis blinatumomab cycles was 2 (range 1-12). The baseline characteristics of B-R, B-NR, and blinatumomab-naïve (B-NV) patients were similar, including pre-apheresis disease burden and receipt of maintenance therapy following brexu-cel infusion (Table 1). Seventy percent (N= 62) of the blinatumomab-exposed patients were B-R, while 30% (N=26) were B-NR. Rates of CR/CRi at day 28 following brexu-cel infusion were similar between B-R, B-NR, and B-NV patients (79% vs 84% vs 78%, respectively). Most of these remissions were negative for measurable residual disease (MRD), with similar MRD negativity rates in the three groups (table 2). 1-year DOR and PFS were significantly higher in the B-NV group compared to B-R or B-NR (77% vs 49% vs 50%, p<.0001; 60% vs 37% vs 30%, p<.0001). B-NV and B-R had better 1-year survival compared to B-NR (71% vs 65% vs 32%, p<.0001). There were more CD19-negative relapses following brexu-cel in B-NR (29%) and B-R (18%) compared to B-NV patients (8%), although this was not statistically significant. Conclusions: Brexu-cel induced deep responses in a majority of adults with r/r B-ALL, irrespective of prior exposure or response to blinatumomab. Similar to data published by the pediatric CAR-T cell groups, our data draw speculation that adult patients who did not respond to blinatumomab experience shorter overall survival following brexu-cel compared to those who responded to or did not receive blinatumomab. This should be confirmed in a larger, prospective clinical trial. Because this analysis could not account for patients who achieved durable remission after blinatumomab, these differences may not reflect superiority of sequencing brexu-cel before blinatumomab. The higher number of CD19-negative relapses in the blinatumomab-exposed cohort add to the interest in pursuing strategies to address antigen escape following CAR-T cell therapy directed against a previously targeted antigen.

Introduction: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). Bridging therapy, defined as anti-leukemia therapy given between apheresis and lymphodepleting chemotherapy, was permitted on the pivotal ZUMA-3 trial. The optimal bridging therapy is unknown in this setting. Here we report patient and disease characteristics in those receiving bridging therapies prior to brexu-cel and the impact of bridging on clinical outcomes in a large multicenter cohort. Methods and Results: ROCCA includes 25 US institutions contributing retrospective data from 152 B-ALL patients treated with standard of care brexu-cel between 2021-2023. Ninety-nine patients (65%) received bridging therapy, while 53 patients (35%) received no bridging therapy. Bridging therapy consisted of cytotoxic chemotherapy ( n=65, 66%), immunotherapy ( n=26, 26%; 23 inotuzumab, 3 blinatumomab), tyrosine kinase inhibitors (TKI) ( n=20, 20%; 16 ponatinib), steroids only ( n=10, 10%), and intrathecal chemotherapy ( n=22, 22%). The median age of the cohort was 46 (IQR 32-61). Patients were heavily pre-treated with a median of 4 prior lines of therapy. The median days from apheresis to infusion was 33 (IQR 26-42). 119 patients had known pre-apheresis blast counts; the bridging group had higher pre-apheresis blast burden, with 21 of 76 patients (28%) having ≥ 50% blasts compared to only 5 of 43 patients (12%) in the no bridging group ( p=0.02). In addition, more patients who received bridging had pre-apheresis extramedullary disease (32% vs. 15%, p=0.02). All other baseline characteristics were similar between the two groups (Table 1). Fifty-four (54%) patients had response assessment after bridging therapy and prior to brexu-cel infusion. In patients who received inotuzumab for pre-apheresis active disease, defined as ≥ 5% blasts, 6 of 13 (46%) who had post-bridging assessment achieved a complete response (CR; 5 measurable residual disease (MRD)+, 1 MRD-), with a mean proportional reduction in blast burden of 46% from baseline. In contrast, after chemotherapy bridging, only 2 of 16 patients (13%) with pre-apheresis active disease had a CR. Patients receiving chemotherapy bridging had a mean proportional increase in blast burden of 4.4%. In recipients of TKI bridging, 2 of 4 patients (50%) with pre-apheresis active disease had a CR. Compared to no bridging, patients in the bridging group had similar rates of grade 3 or 4 CRS (9% bridging vs. 8% no bridging, p=0.73) and grade 3 or 4 ICANS (34% vs. 26%, p=0.32). In univariate analysis, there was no statistically significant difference in day 28 response with 63 patients (72%) achieving MRD- complete response in the bridging group as compared to 36 patients (78%) in the no bridging group ( p=0.60). Non-relapse mortality was similar between the two groups (17% bridging vs. 9% no bridging, p=0.20). Overall survival (OS) and progression-free survival (PFS) were superior in the no bridging group: 1-year OS 74.7% vs 56.8% (log-rank p=0.04), and 1-year PFS 57.3% vs 41.7% (log-rank p=0.04). In a multivariate analysis stratified by bridging and pre-apheresis disease burden, patients with pre-apheresis blasts ≥ 5% and bridging had worse survival than ≥ 5% blasts and no bridging: 1-year OS 45.3% vs. 87.5% and 1-year PFS 27.7% vs. 64.3% (Figure 1). However, patients with < 5% blasts had similar survival regardless of bridging. Conclusions: In our real-world analysis, adults with R/R B-ALL receiving bridging therapy had a higher disease burden at baseline. Despite greater baseline disease, there were no significant differences in toxicity and day 28 response in those receiving bridging therapy vs. not. While survival was inferior in patients with pre-apheresis active disease who received bridging, this may be confounded by the degree of tumor burden. In patients with < 5% blasts pre-apheresis, bridging did not impact survival. Furthermore, inotuzumab bridging demonstrated the most significant disease debulking. However, the comparisons in this study are limited by the variability in practice for post-bridging disease reassessment and the small proportion of patients with active disease who did not receive bridging. A more uniform approach to peri-CAR disease assessment would enable more robust study of optimal bridging strategies.

AbstractBackgroundDespite recent approval of several new agents, relapsed acute lymphoblastic leukemia (ALL) remains challenging to treat. Sapanisertib (MLN0128/TAK‐228) is an oral TORC1/2 inhibitor that exhibited preclinical activity against ALL.MethodsWe conducted a single‐arm multi‐center Phase II study of sapanisertib monotherapy (3 mg orally daily of the milled formulation for 21 days every 28 days) in patients with ALL through the Experimental Therapeutics Clinical Trials Network (NCI‐9775).ResultsSixteen patients, 15 of whom were previously treated (median 3 prior lines of therapy), were enrolled. Major grade 3–4 non‐hematologic toxicities included mucositis (3 patients) and hyperglycemia (2 patients) as well as hepatic failure, seizures, confusion, pneumonitis, and anorexia (1 patient each). Grade >2 hematological toxicity included leukopenia (3), lymphopenia (2), thrombocytopenia, and neutropenia (1). The best response was stable disease in 2 patients (12.5%), while only 3 patients (19%) were able to proceed to Cycle 2. Pharmacokinetic analysis demonstrated drug exposures similar to those observed in solid tumor patients. Immunoblotting in serially collected samples indicated limited impact of treatment on phosphorylation of mTOR pathway substrates such as 4EBP1, S6, and AKT.ConclusionIn summary, single‐agent sapanisertib had a good safety profile but limited target inhibition or efficacy in ALL as a single agent. This trial was registered at ClinicalTrials.gov as NCT02484430.

Abstract Asparaginase is a key component of pediatric-inspired regimens in young adults with acute lymphoblastic leukemia (ALL). Truncation of asparaginase therapy is linked to inferior outcomes in children with ALL. However, a similar correlation in adults is lacking. Here, we studied the prevalence and risk factors associated with pegylated (PEG)-asparaginase discontinuation in young adults with ALL treated on the US intergroup Cancer and Leukemia Group B (CALGB) 10403 study and examined the prognostic impact of early discontinuation (ED) (defined as <4 of 5 or 6 planned doses) on survival outcomes. The analysis included 176 patients who achieved complete remission and initiated the delayed intensification (DI) cycle. The median number of PEG-asparaginase doses administered before DI was 5 (range, 1-6), with 57 (32%) patients with ED. The ED patients were older (median, 26 vs 23 years; P = .023). Survival was apparently lower for ED patients compared with those receiving ≥4 doses, but this finding was not statistically significant (hazard ratio [HR], 1.82; 95% confidence interval [CI], 0.97-3.43; P = .06), with corresponding 5-year overall survival (OS) rates of 66% and 80%, respectively. In patients with standard-risk ALL, the ED of PEG-asparaginase adversely influenced OS (HR, 2.3; 95% CI, 1.02-5.22; P = .04) with a trend toward inferior event-free survival (EFS) (HR, 1.84; 95% CI, 0.92-3.67; P = .08). In contrast, there was no impact of early PEG-asparaginase discontinuation on OS (P = .64) or EFS (P = .32) in patients with high-risk disease based on the presence of high-risk cytogenetics, Ph-like genotype, and/or high white blood cell count at presentation. In conclusion, early PEG-asparaginase discontinuation is common in young adults with ALL and may adversely impact survival of patients with standard-risk ALL.

Abstract Transcriptome sequencing has identified multiple subtypes of B-progenitor acute lymphoblastic leukemia (B-ALL) of prognostic significance, but a minority of cases lack a known genetic driver. Here, we used integrated whole-genome (WGS) and -transcriptome sequencing (RNA-seq), enhancer mapping, and chromatin topology analysis to identify previously unrecognized genomic drivers in B-ALL. Newly diagnosed (n = 3221) and relapsed (n = 177) B-ALL cases with tumor RNA-seq were studied. WGS was performed to detect mutations, structural variants, and copy number alterations. Integrated analysis of histone 3 lysine 27 acetylation and chromatin looping was performed using HiChIP. We identified a subset of 17 newly diagnosed and 5 relapsed B-ALL cases with a distinct gene expression profile and 2 universal and unique genomic alterations resulting from aberrant recombination-activating gene activation: a focal deletion downstream of PAN3 at 13q12.2 resulting in CDX2 deregulation by the PAN3 enhancer and a focal deletion of exons 18-21 of UBTF at 17q21.31 resulting in a chimeric fusion, UBTF::ATXN7L3. A subset of cases also had rearrangement and increased expression of the PAX5 gene, which is otherwise uncommon in B-ALL. Patients were more commonly female and young adult with median age 35 (range,12-70 years). The immunophenotype was characterized by CD10 negativity and immunoglobulin M positivity. Among 16 patients with known clinical response, 9 (56.3%) had high-risk features including relapse (n = 4) or minimal residual disease >1% at the end of remission induction (n = 5). CDX2-deregulated, UBTF::ATXN7L3 rearranged (CDX2/UBTF) B-ALL is a high-risk subtype of leukemia in young adults for which novel therapeutic approaches are required.

PURPOSE Chemotherapy outcomes in older patients with Philadelphia (Ph) chromosome–negative B-acute lymphoblastic leukemia (ALL) are very poor. Here, we evaluated blinatumomab as induction and consolidation therapy followed by prednisone, vincristine, 6-mercaptopurine, and methotrexate (POMP) maintenance chemotherapy in this patient population. PATIENTS AND METHODS Patients were treated at National Clinical Trial Network sites. Eligibility criteria included age ≥ 65 years and newly diagnosed Ph chromosome–negative B-ALL. Patients received blinatumomab as induction for one-two cycles until attainment of response (complete remission (CR) and CR with incomplete count recovery). Patients then received three cycles of consolidation with blinatumomab followed by 18 months of POMP maintenance chemotherapy. Eight doses of intrathecal methotrexate were administered as central nervous system prophylaxis. RESULTS Twenty-nine eligible patients were enrolled. The median age was 75 years, and the median bone marrow blast count at diagnosis was 87%. Cytogenetic risk was poor in 10 patients (34%), and five of 14 patients (36%) tested had the Ph-like ALL gene signature. Nineteen patients (66%; 95% CI, 46 to 82) achieved CR. Kaplan-Meier 3-year disease-free survival and overall survival estimates were 37% (95% CI, 17 to 57) and 37% (95% CI, 20 to 55), respectively. CONCLUSION Blinatumomab was well tolerated and effective in the treatment of older patients with newly diagnosed Ph chromosome–negative B-ALL, including patients with poor-risk cytogenetics. The 3-year disease-free survival and overall survival results are encouraging and suggest that this approach should be further explored.