Oluwole, Olalekan O.

Abstract The use of chimeric antigen receptor (CAR) T-cell therapy is increasing for adult B-cell acute lymphoblastic leukemia (B-ALL), with 3 CD19 CAR T-cell products commercially available. Several key clinical questions related to best practices for CAR T-cell administration in this population exist, and limited prospective randomized trials have been conducted to fill these knowledge gaps. Thus, to help guide clinical practice, we conducted a modified Delphi study to develop and validate consensus recommendations on the administration of commercially available CAR T-cell therapy for adults with B-ALL. Consensus panelists (n = 9) included principal investigators (PIs) from Real World Outcomes Collaborative of CAR T-Cell Therapy in Adult ALL (ROCCA) consortium sites and were selected based on expertise and CAR T-cell center volume. Final panel consensus recommendations were distributed for rating by the remaining PIs from ROCCA consortium sites, which served as the validation group (n = 27). Consensus topics included patient selection, bridging and pre–CAR T-cell leukemia staging, lymphodepletion, and CAR T-cell treatment setting, specific toxicity prevention and management, post–CAR T-cell response assessment and disease monitoring, and the role of consolidation and/or maintenance therapies after CAR T-cell therapy. Initially, 58 recommendation statements were evaluated for consensus. After 2 panel meetings, a total of 34 statements achieved consensus rating among the expert panel. After rating by the validation group, all but 1 recommendation statement continued to meet consensus, for a total of 33 consensus recommendation statements on the administration of CAR T-cell therapy in adult B-ALL.

Abstract In a real-world analysis of brexucabtagene autoleucel recipients with relapsed/refractory B-cell acute lymphoblastic leukemia (N = 278), lack of response to prior blinatumomab correlates with significantly worse following chimeric antigen receptor T-cell therapy outcomes.

Abstract Introduction Obecabtagene autoleucel (obe-cel) and brexucabtagene autoleucel (brexu-cel) are CD19 targeted chimeric antigen receptor T cell (CAR-T) therapies, approved for the treatment of adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). Mechanistic differences between obe-cel and brexu-cel including differing costimulatory domains (4-1BB vs. CD28), CD19 binding domains (intermediate vs. high affinity) and split dose (Days 1 and 10) vs. single infusion may impact in-vivo cellular kinetics that translate into variant clinical outcomes. In pivotal trials, obe-cel resulted in lower rates of severe cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) compared to brexu-cel with comparable efficacy (Roddie et al., NEJM 2025; Shah et al., Lancet 2021). Real-world utilization and outcomes with obe-cel are unknown given the relatively recent approval. Methods The ROCCA database, comprising real world data from patients (pts) with r/r ALL treated at 40 North American institutions was utilized in this analysis. Pts with r/r ALL were eligible if they were apheresed for obe-cel since its approval (11/8/2024) or brexu-cel over a comparable period (since 8/1/24) and had at least 30 days of follow up. Data cut off was 7/15/2025. CRS/ICANS were graded per ASTCT criteria. Measurable residual disease (MRD) was assessed by flow cytometry and/or next generation sequencing per institutional standards. Results 38 pts have undergone apheresis for obe-cel (36 infused, all received both infusions) and 54 (53 infused) for brexu-cel over the study period. Pts in the obe-cel and brexu-cel cohorts had the following baseline characteristics: median age, 47 vs. 39 years; ECOG 2+, 15% vs. 26%; Ph+ disease, 24% vs 13%; KMT2Ar, 0 vs. 4%; TP53m, 11% vs 11%, and hypodiploid karyotype, 5% vs 6%. The following prior treatment patterns were observed: median lines of therapy before CAR-T 3 vs. 3; prior SCT 24% vs. 30%, prior blinatumomab 68% vs. 46%, prior inotuzumab 45% vs. 30%. At apheresis, active disease (>5% bone marrow blasts) was present in 47% vs. 55% of obe-cel and brexu-cel pts, respectively; the remainder were in CR (with 18% vs. 22% in MRD- CR, respectively). Among obe-cel (n= 35 [92% of cohort]) and brexu-cel (21 [38% of cohort] pts with disease re-assessment prior to lymphodepletion (LD), 31% vs. 43% had active BM disease, respectively; few pts (24% vs. 17%) had >20% marrow disease burden prior to LD. CAR-mediated toxicity differed significantly between the cohorts. CRS occurred in 56% of obe-cel pts compared to 94% of brexu-cel pts (p < 0.0001). There were no Gr3+ CRS events among the obe-cel pts; 3 (6%) brexu-cel pts had Gr3+ CRS (p = 0.27). ICANS occurred in 17% of obe-cel pts vs. 51% of brexu-cel pts (p = 0.001). Gr3+ ICANS occurred in 6% of obe-cel vs. 32% of brexu-cel pts (p = 0.0027). Among the obe-cel pts, CRS occurred in 31% after the first infusion and 46% after the second; ICANS occurred in 3% after the first infusion and 15% after the second. Prolonged Gr4 neutropenia (ANC < 500 cells/uL beyond day 30 from infusion) occurred in 24% of obe-cel vs. 28% of brexu-cel pts (p = 0.73). Deaths within the first 28 days of infusion occurred in 0 obe-cel pts and 4 brexu-cel pts (2 of infection, 1 of infection/brain bleed, and 1 of liver failure in the setting of Gr4 CRS and HLH). Response rates were high and did not significantly differ between cohorts (p = 0.85). Among the 31 obe-cel pts with available response data, 25 (81%) achieved an MRD- CR/CRi, 3 (10%) had an MRD+ CR/CRi, 2 (6%) had a CR/CRi with unknown MRD, and 1 (3%) did not respond. Among 41 brexu-cel pts with available response data, 33 (80%) had an MRD- CR/CRi, 4 (10%) an MRD+ CR/CRi, and 4 (10%) CR/CRi with unknown MRD. Conclusion Pts selected for obe-cel apheresis were similar to those for brexu-cel over the study period (noting that not all centers had access to obe-cel during this time). Similar to clinical trial results, obe-cel was associated with lower rates of CRS/ICANS. Rates of MRD-negative CR were high and did not differ between cohorts. A larger sample and longer follow up are required for further analyses; we anticipate a cohort of ~75 obe-cel treated pts by the annual meeting and will provide updated data.

Abstract Introduction: Brexucabtagene autoleucel (Brexu-cel) is a CD19-targeted chimeric antigen receptor (CAR-)T cell therapy approved for treatment of relapsed/refractory (r/r) B-ALL. Brexu-cel's approval was founded on data from the ZUMA-3 trial, in which 78 patients (pts) were treated at the pivotal dose of 1x10e6 CAR-T cells/kg, resulting in a complete remission (CR) rate of 73%. Three-year follow-up from ZUMA-3 demonstrated median relapse-free and overall survival (RFS/OS) of 11.6 and 25.6 months (mos) for all treated pts. Amongst responders, the median OS was 60.4 mos for those who did not receive a subsequent allogeneic hematopoietic cell transplant (HCT) (n=43), but only 36.3 months for those who did (n=14). This has led some to conclude that HCT may not be beneficial following brexu-cel therapy for r/r B-ALL; however, it must be noted that 29 (37%) of the pts treated on ZUMA-3 received brexu-cel for post-HCT relapse. T cells collected from individuals who relapse in the post-HCT setting are largely of donor origin, making the CAR-T product comparable to a genetically modified donor lymphocyte infusion (DLI). The immunology at play in this scenario may be different from that in which CAR-T cells are of truly autologous origin. Methods: The Real-World Outcomes Collaborative for CAR-T in ALL (ROCCA) consortium database includes pt characteristics and outcomes of brexu-cel therapy given as standard-of-care across 41 US institutions. We identified pts who achieved an MRD negative (neg) CR by either flow cytometry (minimum sensitivity 10e-4) or NGS following brexu-cel for r/r Ph neg B-ALL and categorized them into three groups with regard to use of HCT: Never HCT, Pre-CAR HCT, or Post-CAR HCT. Pts who received second HCT following brexu-cel for post-HCT relapse (n=9) were excluded. Pt/disease characteristics, RFS, and OS were assessed for each group, landmarked at 73 days after brexu-cel infusion (the median time to consolidative allogeneic HCT). Results: In the ROCCA database we identified 165 pts who achieved MRD neg CR following brexu-cel, amongst whom 69 never underwent HCT, 49 were transplanted pre-CAR (ie, brexu-cel served as a genetically modified DLI), and 47 underwent post-CAR consolidative HCT while in CR. The median follow-up is 373 days. The median age was higher in the Never HCT group (49, range 19-83) in comparison with the Pre-CAR HCT (40, 24-72) and Post-CAR HCT (34, 18-70) groups. Thirty-five percent were >60yo in the Never HCT group vs 20% in the Pre-CAR HCT and 9% in the Post-CAR HCT groups. Ph-like disease was present in 38%, 29%, and 43% of the Never HCT, Pre-CAR HCT, and Post-CAR HCT groups, respectively (p=0.35). No significant differences were observed in pre-apheresis bone marrow blasts, presence of CNS disease at apheresis, prior blinatumomab or inotuzumab treatment, or use of bridging therapy across the groups, though there was a higher prevalence of non-CNS extramedullary disease in the Pre- and Post-CAR HCT groups (32, 39%) vs the Never HCT group (13%) (p=0.004). A minority of pts in all groups were deemed to be in MRD neg CR prior to apheresis (6-20%). Median RFS was 260 days in the Never HCT group and not reached in the Pre- and Post-CAR HCT groups (p=0.002), with respective 1-yr RFS of 38%, 64%, and 67%. Median OS was not reached in any group and was similar for all at 1-yr at 68-79% (p=0.13). Characteristics of those in the Never HCT group who were least likely to relapse included age >60 (OR 0.22, CI 0.07-0.73 vs age 18-39, p=0.024) and those with non-Ph-like B-ALL (OR 0.33, CI 0.12-0.94, vs Ph-like, p=0.037) in univariate analyses. Conclusions: Real-world data regarding outcomes following brexu-cel therapy allow evaluation of the role for consolidative allogeneic HCT, which remains one of the most important unresolved questions in the use of CAR-T therapy for r/r B-ALL. This analysis demonstrates that a first consolidative HCT after achieving MRD neg CR with brexu-cel is associated with a significant decrease in relapse. Additionally, use of brexu-cel for post-HCT relapse is also associated with a significantly lower risk of relapse compared with those who never received an allogeneic HCT. With the current duration of followup, OS is not significantly different across the three groups. These data suggest there is a benefit for relapse-free survival in pts receiving an allogeneic HCT at some point in the course of treatment for r/r Ph neg B-ALL.

Abstract Background: Despite the promising efficacy of CAR-T for patients with relapsed or refractory (R/R) large B-cell lymphomas (LBCL), more than 60% of patients will relapse, the majority of which occur in the first 6 months. Approximately 30% of patients with LBCL treated with CAR-T achieve a partial response (PR) on day 30 (D30) PET-CT assessment. Of patients in a D30 PR, 70% will eventually progress, yet the standard of care remains close observation. Early consolidative treatment strategies utilizing therapies with a different mechanism of action may improve outcomes, but there are currently no reliable biomarkers. Epcoritamab (Epco), a bispecific antibody directed against CD20 and CD3, has been approved by the FDA for LBCL patients who relapse after at least 2 lines of therapy. By treating prior to overt relapse, Epco has the potential to salvage inadequate responses post CAR-T. This study is a trial-in-progress that will evaluate the efficacy of epco compared to observation for patients with LBCLs achieving a PR on D30 post CAR-T PET-CT assessment. Methods This is an investigator-initiated, randomized, phase II, multicenter, open-label study (NCT06238648) evaluating epco monotherapy for a fixed duration of 12 cycles compared to observation for LBCL patients with D30 PR after standard of care CAR-T. A maximum of 120 patients will be randomized 1:1 to epco or observation across 10 academic centers. Stratification factors include line of CAR-T (second vs third line) and costimulatory domain (CD28 vs 4-1BB). Key inclusion criteria include PET evidence of a D30 PR. non-bulky disease ( <7.5cm), ANC of >1000, hemoglobin >7 g/dL if asymptomatic or >8 if symptomatic, platelet count >50,000. G-CSF, pRBCs and platelet transfusions are allowed. Key exclusion criteria include ongoing or uncontrolled CRS or ICANS, and active or symptomatic CNS disease. This study is available to all eligible patients, regardless of race, gender, or ethnic origin. To adapt to current practices, prior bispecific antibody exposure is allowed if used as holding or bridging therapy without disease progression. Epco is administered subcutaneously at a dose of 0.16mg on day 1, 0.8mg on day 8, prior to full dose of 48mg on day 15. Epco is administered weekly in 28 day cycles (C) for C1-3, on day 1 and 15 of C4-9 and on day 1 of C10-12. PET-CT response is assessed by the 2014 Lugano criteria after 2 cycles, and then every 3 months during active treatment. The primary objective is efficacy, measured as conversion from D30 PR to CR. The secondary endpoints include frequency and severity of treatment emergent adverse events, ORR, duration of response, duration of complete response, progression free survival, event free survival, and overall survival. Peripheral blood samples will be collected pre-treatment and during treatment to assess for biomarkers of response and resistance and CAR-T persistence. The study was activated in January 2024 and recruitment is ongoing.

PURPOSE Off-the-shelf, allogeneic CD19 chimeric antigen receptor (CAR) T-cell products may improve access to treatment versus autologous ones. We report the phase I experience of the allogeneic CD19 CAR T-cell product cemacabtagene ansegedleucel (cema-cel) and its predecessor, ALLO-501, in CD19 CAR T-naïve patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). METHODS In the ALPHA2/ALPHA studies, the safety and efficacy of allogeneic CD19 CAR T cells were evaluated in CD19 CAR T treatment-naïve patients with R/R LBCL. Patients received healthy donor-derived, human leukocyte antigen–unmatched cema-cel/ALLO-501 following a 3-day lymphodepletion regimen of fludarabine (30 mg/m 2 once daily), cyclophosphamide (300 or 500 mg/m 2 once daily), and escalating doses of the anti-CD52 monoclonal antibody, ALLO-647. RESULTS As of September 26, 2024, 33 CD19 CAR T-naïve patients with LBCL (median age, 66 years; median number of previous therapies, 3) received allogeneic CAR T cells. CAR T-cell expansion was observed following infusion, with persistence observed up to 4 months. The overall and complete response (CR) rates were 58% and 42%, respectively; the median duration of response in patients with a CR was 23.1 months. The most common treatment-emergent adverse events were hematologic toxicities. No cases of graft-versus-host disease, immune effector cell–associated neurotoxicity syndrome, or grade ≥3 cytokine release syndrome were reported. CONCLUSION Allogeneic CD19 CAR T cells demonstrated promising overall and durable CR rates with a manageable safety profile in CD19 CAR T-naïve patients with R/R LBCL, supporting additional evaluation of cema-cel in patients with LBCL.

ZUMA-12 is a multicenter phase 2 study evaluating axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy as part of first-line treatment for high-risk large B-cell lymphoma (LBCL). In the primary efficacy analysis (n = 37; median follow-up, 15.9 months), axi-cel demonstrated a high rate of complete responses (CR; 78%) and a safety profile consistent with prior experience. Here, we assessed updated outcomes from ZUMA-12 in 40 treated patients after ≥3 years of follow-up. Eligible adults underwent leukapheresis, lymphodepleting chemotherapy, and axi-cel infusion (2 × 106 CAR T cells/kg). Investigator-assessed CR, objective response, survival, safety, and CAR T-cell expansion were assessed. The CR rate among response-evaluable patients (n = 37) increased after the primary analysis to 86% (95% confidence interval [CI], 71%-95%), with a 92% objective response rate. After a median follow-up of 47.0 months (range, 37.1-57.8 months), 36-month estimates (95% CI) of duration of response and event-free, progression-free, and overall survival were 81.8% (63.9%-91.4%), 73.0% (55.6%-84.4%), 75.1% (57.5%-86.2%), and 81.1% (64.4%-90.5%), respectively. In total, 4 patients had new malignancies, 2 occurring after the data cutoff of the primary analysis; none were axi-cel–related. Eight patients died on study, 2 of whom died from nonrelapse mortality causes. After long-term follow-up, axi-cel demonstrated a high durable response rate, with no new safety signals after the primary analysis, suggestive of an effective first-line therapy with curative intent in high-risk LBCL. Further assessments are needed to determine its benefit vs standard of care. This trial was registered at clinicaltrials.gov, as NCT03761056.

Introduction: Brexucabtagene autoleucel (brexu cel) is a CD19-targeted chimeric antigen receptor (CAR) T cell therapy approved for the treatment of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). Some patients (pts) proceed with a consolidative allogeneic hematopoietic cell transplant (HCT) after breux cel. We do not know which pts can safely avoid a consolidative HCT and its associated morbidity. Methods: We conducted a retrospective cohort study utilizing the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA) dataset. ROCCA is a registry of brexu cel pts in 32 centers in North America. We defined complete remission (CR) as < 5% blasts in the bone marrow and no central nervous system (CNS) or extramedullary (EM) disease on or around D28 after brexu cel. We defined measurable residual disease negative (MRD-) CR as CR and no abnormal blasts in the bone marrow by multiparameter flow cytometry, quantitative polymerase chain reaction, ClonoSeq next generation sequencing (NGS), or other sequencing modalities with lower sensitivity. ClonoSeq NGS has a sensitivity of 10-6, while the other modalities have a sensitivity of at least 10-4. We defined progression free survival (PFS) as the time from CAR-T infusion to relapse or death, censored at the date of last follow-up. Statistical analyses were performed in R. Univariable Cox proportional hazards regression analyses were performed to determine the association of pre-specified variables with PFS. Variables known to be associated with CAR T outcomes in ALL were entered into a multivariable model. HCT was incorporated as a time-varying covariate. Results: During the study period, 281 pts were infused with brexu cel. We focused our analysis on 172 (61%) pts with confirmed MRD- CR on D28, as that is the group with clinical equipoise regarding maintenance strategy. 38 (22%) of those pts received a consolidative HCT, 30 (17%) received another form of maintenance therapy (primarily tyrosine kinase inhibitors for Philadelphia (Ph)-chromosome positive ALL), and 104 (60%) pts received no maintenance therapy. Pts who underwent consolidative HCT were younger (median age 35 years) than those who received no maintenance (42y) (p = 0.023) and were less likely to have a history of prior HCT (13% vs. 47%, p < 0.001). No differences were observed with respect to sex, TP53 mutation status, prior inotuzumab (ino) or blinatumomab (blina) exposure, disease burden prior to CAR, or development of any cytokine release syndrome (CRS) or any neurotoxicity with brexu cel. We performed univariable Cox proportional hazard regression analyses among pts in MRD- CR on D28, excluding those who received other maintenance therapy besides HCT; the median follow up was 8.1 months. In univariable analyses, D28 MRD negativity by ClonoSeq NGS (versus MRD negativity by other, less sensitive methods), development of CRS, and pre-CAR BM blasts < 5% were associated with improved PFS; prior ino exposure was negatively associated with PFS (p < 0.05). Age, sex, Ph status, TP53 status, and neurotoxicity development were not associated with PFS. In a multivariable model incorporating ALL type, prior HCT, prior ino/blina, and pre-CAR blast burden, as well as consolidative HCT as a time-varying covariate, only MRD negativity by ClonoSeq NGS with at least 10-6 sensitivity retained statistical significance (PFS hazard ratio 0.34, 95% confidence interval (CI) 0.15-0.77, p = 0.005). Pts who were MRD- by ClonoSeq NGS on D28 and received no maintenance had favorable 6m PFS of 76% (95% CI: 59-98%) and OS of 100% with a median follow up of 6.3 months in this subgroup. Among those in MRD- CR by NGS, HCT as a time-varying covariate was not associated with improved PFS (HR 0.6, p = 0.6). Conclusions: In a large real-world cohort of adults with R/R B-ALL infused with brexu cel, we identified practice variation regarding the use of consolidative HCT. Among brexu cel recipients who entered an MRD- CR, we identified ClonoSeq NGS MRD negativity as a novel predictive factor of favorable oncologic outcomes, even without a consolidative HCT. Similar results have been obtained in pediatric ALL patietns ftreated with 41BB-based tisagenleucleucel (Pulsipher et al., Blood Cancer Discovery 2022). Longer follow-up is needed to validate the safety of omitting consolidative HCT in such pts, but these results encourage the potential for definitive therapy with brexu cel when D28 ClonoSeq NGS MRD is negative.

Introduction: Brexucabtagene Autoleucel (brexu-cel) is the first CD19-targeting chimeric antigen receptor (CD19.CAR) T-cell therapy approved for the treatment of relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) in adult (≥18 yo) patients (pts) based on results from the ZUMA-3 trial. However, data on the safety and efficacy of CAR-T cells in older pts (≥60 yo) remains limited, with only 8 pts >65 yo enrolled in the ZUMA-3 trial. We evaluated the treatment characteristics and outcomes with use of brexu-cel amongst patients ≥60 yo in the Real-World Outcomes Collaborative for CAR-T in ALL (ROCCA) consortium database. Methodology: ROCCA is a consortium of over 30 U.S.-based institutions with a database of adult pts with B-ALL who received brexu-cel as standard of care therapy. We identified pts ≥60 yo and further stratified them into two cohorts: 60-69 yo and ≥70 yo. Outcomes of interest included OS, PFS, ORR, and toxicities (CRS and ICANS). Both OS and PFS were calculated from the day of brexu-cel infusion. Response assessment occurred on day +28, and MRD evaluation was per institutional practices. CRS and ICANS were graded according to the American Society for Transplantation and Cellular Therapy criteria. Results: Of 280 brexu-cel recipients in the ROCCA database, 73 (26%) were ≥60 yo, of which 58 (79%) were between 60-69 yo and 15 (21%) were ≥70 yo. Among pts ≥60 yo, the median age at infusion was 65 (range 60-81). Pts were heavily pretreated with a median of 3 prior lines of therapy (range 2-9). Prior therapies included: allogeneic HSCT (38%), inotuzumab ozogamicin (41%), and blinatumomab (62%). Forty pts (55%) had Ph-negative B-ALL, 24 (33%) had Ph+ B-ALL and 9 (12%) had Ph-like B-ALL. When grouped by HCT-CI equal to 0, 1-2 or ≥3, a higher proportion of pts ≥60 yo had HCT-CI ≥3 (19% vs. 7% in <60 yo; p=0.004). Pre-apheresis, 33 pts (45%) had active disease (>5% marrow blasts or extramedullary disease), 34 (47%) were in CR (of whom 14 were MRD-negative) and 6 had unknown disease status. Following brexu-cel, 43 (59%) achieved MRD-negative CR, 20 (27%) had MRD + or CR with unknown MRD status, 6 (8%) had refractory disease and 5 had no disease evaluation available. The ORR was similar between pts 60-69 and ≥70 yo (MRD-negative CR rate: 58% vs 61%, r/r to brexu-cel: 9% vs 6%) and was comparable to pts <60 yo (MRD-negative CR 66%; r/r disease of 9%). The rate of all grade ICANS was higher in pts ≥70 (77%) than in pts 60-69 (47%) or pts <60 (49%), with grade 1-2 ICANS occurring at a significantly higher rate in pts ≥70 (44% vs. 20% in 60-69 and 20% in <60, p=0.049). Grade 3-4 ICANS were similar between the groups: 33%, 27% and 29% in the ≥70, 60-69, and <60 groups, respectively. Conversely, rates of CRS were similar across age groups (80-84%). There was no statistically significant difference in the rate of grade 3-4 CRS which was 17% in pts ≥70, 4% in pts 60-69, and 11% in pts <60 yo. With a median follow-up of 332 days (range 8-936 days) from infusion, pts ≥60 yo had a median PFS of 395 days compared to 547 days in pts <60 yo. Median PFS was lower in the ³70 yo (231 days) compared to 677 in the 60-69 yo cohort. No statistically significant difference was found between the <60 and ≥60groups in 6- and 12-month PFS rates (6 months PFS: 66% vs 64%, p=0.77 and 12 months PFS: 57% vs 57%, p=1.00). When pts ≥60 yo were stratified by age, pts ≥70 yo had similar 6-month PFS compared to other age groups but significantly lower 12-month PFS (38%; vs. 64% in pts 60-69and 57% in pts <60, p=0.001). Median OS was not reached in any of the age groups, and there was no statistically significant difference in 6-month OS (72% in ≥ 70 vs. 82% in the 60-69 vs. 82% in <60, p=0.14) or 12-months OS (61% in ≥ 70 vs. 69% in 60-69 vs. 73% in <60, p=0.18). Conclusion: This is the largest study to date of older B-ALL pts receiving CAR-T cells. We observed that older pts, particularly those aged 60-69, have similar outcomes to younger pts. However, pts ≥70 yo had lower median and 12-month PFS when compared to younger patients. Additionally, pts ≥70 yo had higher rates of grades 1-2 ICANS. An important limitation of this analysis is the potential selection bias among clinicians when selecting older patients for this treatment. Longer follow-up, including inclusion of additional pts ≥70 yo is needed to confirm these results, and further studies are needed to identify the optimal approach for use of CAR T-cell therapy in patients in this age group.

The NCCN Guidelines for the Management of Immunotherapy-Related Toxicities are intended to provide oncology practitioners with guidance on how to manage the wide-ranging and potentially fatal toxicities that may occur with cancer immunotherapy. The guidelines address immune-related adverse events related to immune checkpoint inhibitors, CAR T-cell therapies, and lymphocyte engagers (which include T-cell–engaging bispecific antibodies). These NCCN Guidelines Insights highlight recent guideline updates pertaining to the management of emerging toxicities related to cancer immunotherapy.