Hilal, Talal

Purpose Neutropenic diet (ND) has historically been recommended to reduce infectious complications in patients with cancer. Although its use has declined over the past decade, recent studies, particularly in patients undergoing hematopoietic stem-cell transplantation (HSCT), have renewed concern regarding the safety of a liberalized diet (LD). We performed a meta-analysis of studies comparing ND with LD in patients with cancer. Methods We searched MEDLINE, Embase, and Cochrane databases from inception through January 2026. Comparative studies evaluating ND versus LD in adults or children with cancer were included. Primary outcomes were major infections and bacteremia/fungemia; secondary outcomes were pneumonia, diarrhea, and mortality. Random-effects meta-analyses were performed to calculate pooled relative risks (RRs) with 95% CIs. Results Fifteen studies including 4,320 patients met criteria for analysis. ND was not associated with significant differences in major infections (RR, 1.02 [95% CI, 0.88 to 1.18]; P = .795), bacteremia/fungemia (RR, 0.97 [95% CI, 0.78 to 1.22]; P = .805), pneumonia (RR, 0.98 [95% CI, 0.59 to 1.63]; P = .933), diarrhea (RR, 1.12 [95% CI, 0.96 to 1.31]; P = .159), or mortality (RR, 0.94 [95% CI, 0.77 to 1.15]; P = .632). Sensitivity analyses restricted to randomized controlled trials (RCTs) were consistent. In hematologic malignancy/HSCT studies (9 studies; 1,769 patients), no differences were observed across outcomes. In RCTs limited to these patients (6 studies; 855 patients), ND was associated with lower bacteremia/fungemia risk (RR, 0.67 [95% CI, 0.47 to 0.95]; P = .023), with no differences in other outcomes. Conclusion ND was not associated with reductions in major infections, pneumonia, diarrhea, or mortality compared with LD. These findings do not support routine implementation of ND for patients with short-term neutropenia or lower-risk cancer populations although selected high-risk patients, particularly those undergoing HSCT or experiencing prolonged neutropenia related to hematologic malignancies, may still warrant cautious dietary practices.

Brexucabtagene-autoleucel (brexu-cel) produces high rates of measurable residual disease-negative (MRD-) complete response (CR) in adults with Philadelphia-chromosome positive (Ph+) acute lymphoblastic leukemia (ALL); however, subsequent relapses remain frequent. It is unclear whether maintenance with tyrosine kinase inhibitors (TKIs) can enhance remission durability. We evaluated outcomes among adults with relapsed/refractory Ph+ ALL who received commercial brexu-cel and achieved MRD- CR across 19 U.S. institutions. Considering TKI maintenance as a time-varying covariate, we analyzed outcomes based on receipt of subsequent TKI maintenance versus no maintenance. Patients receiving consolidative transplantation or non-TKI maintenance were excluded. Fifty-one patients were included: 20 received TKI maintenance and 31 received no maintenance. The use of TKI maintenance was associated with a significantly lower 1-year cumulative incidence of relapse (HR 0.12; 95% CI, 0.02-0.88; p=0.037) which translated into improved progression-free survival (PFS, HR 0.19; 95% CI, 0.04-0.85; p=0.029) and a trend towards improved overall survival (OS, HR 0.34; 95% CI, 0.07-1.62; p=0.18). There was no difference in non-relapse mortality (NRM, HR 0.83; 95% CI, 0.12-5.87; p=0.85). This real-world analysis supports the administration of TKI maintenance in Ph+ ALL following achievement of MRD- CR with brexu-cel as a strategy to improve PFS following chimeric antigen receptor T cell therapy.

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.

CD19-directed chimeric antigen receptor (CAR) T-cell therapies have been instrumental in improving outcomes of refractory or relapsed B-cell malignancies. However, there have been safety concerns due to recent reports of second primary malignancies (SPMs) related to CAR T-cell therapies. We reviewed articles from Embase, PubMed, and Cochrane Library records and included SPM case reports as well as cohort studies. Across published cohorts, secondary cutaneous or peripheral T-cell lymphoma (PTCL) after diffuse large B-cell lymphomas (DLBCLs) have been reported at low incidence (generally in the low single-digit percentage range). While CAR T-cell therapy is associated with these rare secondary malignancies and lineage-switch events primarily described in acute leukemia, they are clinically significant and have resulted in increased surveillance. The currently available evidence suggests that most secondary malignancies after CAR T-cell therapy are due to background risk and prior treatment exposures rather than direct CAR T-cell therapy induced oncogenesis. However, rare CAR T-cell therapy-associated second primary T-cell malignancies have been reported. To properly define incidence, mechanisms, and risk factors for CAR T-cell therapy-associated malignancies, continued prospective registry follow-up and additional research will be needed.

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.

Introduction Registrational trials are clinical trials which are used to justify regulatory approval of a new medication by the FDA. However, clinical trials may not be designed around patient-centred outcomes, like overall survival (OS) or quality of life. This disconnect raises concerns about whether current trial designs are truly aligned with the long-term needs and priorities of patients. A comprehensive analysis of trial designs and endpoints is necessary to ensure that future oncological therapies deliver meaningful clinical improvements. Our objective was to describe types of clinical trial design and primary endpoints used for registrational trials, and their trends over time. Research design and methods In this cohort study, the HemOnc database was used to identify registrational trials supporting cancer drug approval from 2004 through 2023. Clinical trial design (escalation, de-escalation, in-class switch, out-of-class switch) and primary endpoint (OS; time-to-event including progression-free survival; response-based endpoint) were characterized. Results Escalation trial designs were more common than in-class switches or out-of-class switches. De-escalation and mixed designs were exceedingly rare. The most common primary endpoint was a composite time-to-event endpoint. Conclusion Most clinical trials leading to FDA approval for cancer-directed therapies employ escalation designs with composite time-to-event endpoints. Designs reflecting paradigm shifts in therapy (in-class switches and out-of-class switches) are sparsely used. This approach raises the concern that trials may increase therapeutic toxicity without delivering meaningful improvements in OS or quality of life.