Real-life data on cefiderocol for Gram-negative infections remain limited. We aimed to evaluate factors associated with mortality in patients treated with cefiderocol either as monotherapy or combination therapy. A retrospective multicenter study using the CEFI-BAC cohort was conducted across 17 Italian centers on adults treated with cefiderocol (January 2021–February 2023). Data included patient characteristics, infections, prescriptions, end-of-treatment (EOT) outcomes, and mortality (in-hospital/30-days). Statistical comparisons were performed using Chi-square/Fisher’s tests and the Mann-Whitney U test. Factors associated with 30-days mortality were analyzed using multivariate Cox regression. Among 243 patients, 65% were male (median age 68 years). Major infections included bloodstream infections (61%, 149/243) and nosocomial pneumonia (14%, 34/243) with Acinetobacter baumannii (64%, 157/243), Pseudomonas aeruginosa (17%, 42/243), and Klebsiella spp. (23%, 57/243) as most common pathogens. Median treatment lasted 10 days (IQR 7–15) with five adverse events reported. Clinical cure at EOT was 59% (143/243). EOT mortality for all patients was 22.5% (50/243), and in- hospital mortality was 40.3% (93/243). Cefiderocol was used in combination therapy in 56% of cases (137/243), mainly for severe infections, including polymicrobial infections (34%, 46/243) and septic shock (27%, 37/243) (Table 1). Monotherapy correlated with higher comorbidity burden. EOT mortality was 17% (18/106) for monotherapy and 23% (32/137) for combination therapy, with no significant differences in in-hospital mortality (36.5%, 35/243 versus 42.9%, 58/243; P = 0.320) or hospitalisation length (40 [IQR 24–72] versus 46 days [IQR 25–76]; P = 0.340). Kaplan-Meier analysis confirmed no significant differences in 30-day mortality (Figure 1). Multivariate Cox regression identified advanced age (aHR: 1.25/year, P = 0.038), prior antibiotics (aHR: 4.31–7.50, P < 0.05), concurrent SARS-CoV-2 infection (aHR: 4.40, P < 0.01), and New Delhi Metallo-beta-lactamase NDM-type infection mechanisms (aHR: 6.42, P = 0.001) as significant predictors of 30-days mortality. The study revealed no differences in efficacy between the use of cefiderocol as monotherapy or combination therapy, despite the former being preferred in patients with more comorbidities which may reflect a cautious approach to minimize drug interactions and toxicity. The lack of significant differences between the two strategies raises questions about the best strategy in severe infections, highlighting the need for a patient individualized approach. Figure 1.30-days in-hospital survival Kaplan-Meier according to therapy (monotherapy versus combination therapy).
7536 Background: Belantamab mafodotin (belamaf) is being studied in combination with bortezomib + dexamethasone (BVd) or pomalidomide + dexamethasone (BPd) in the phase 3 DREAMM-7 (D7; NCT04246047) and DREAMM-8 (D8; NCT04484623) trials, respectively; both enrolled patients (pts) with relapsed/refractory multiple myeloma (RRMM) who had received ≥1 prior line of therapy. D7 compared BVd vs daratumumab + bortezomib + dexamethasone (DVd); D8 compared BPd vs bortezomib + pomalidomide + dexamethasone (PVd). In both trials, belamaf combinations showed significant progression-free survival (PFS) benefits vs comparators. In D7, median PFS (95% CI) was 36.6 mo (28.4-not reached [NR]) with BVd vs 13.4 mo (11.1-17.5) with DVd (HR, 0.41; 95% CI, 0.31-0.53; P <.001). In D8, median PFS (95% CI) was NR with BPd vs 12.7 mo (9.1-18.5) with PVd (HR, 0.52; 95% CI, 0.37-0.73; P <.001). This study compared the efficacy of BPd (D8 active arm) vs DVd (D7 comparator). Methods: The overlapping D7 and D8 RRMM population was analyzed. To align cohorts, D8 BPd pts refractory to any anti-CD38 were excluded, as were D7 DVd pts without prior lenalidomide exposure or pomalidomide-refractory disease. The primary endpoint was PFS. Secondary endpoints included overall survival (OS), minimal residual disease (MRD)–negativity rate, duration of response (DOR), overall response rate (ORR), and time to treatment discontinuation (TTD) with all treatments. This indirect comparison used inverse probability of treatment weighting to match baseline characteristics between DVd and BPd arms, estimating the average treatment effect in the treated population (IPTW-ATT). In the matched population, time-to-event analyses used the Kaplan-Meier method and Cox proportional hazards models. Results: Of 155 pts in the D8 BPd arm and 251 in the D7 DVd arm, 120 and 111, respectively, met inclusion criteria for this analysis. Baseline characteristics were generally balanced after IPTW-ATT. After adjustment, BPd significantly improved PFS vs DVd (median [95% CI], NR [21.1-NR] vs 11.1 mo [6.4-19.1]; HR, 0.41; 95% CI, 0.25-0.65; P =.0002). Median (95% CI) DOR was NR (24.9-NR) with BPd vs 10.5 mo (5.0-17.7) with DVd; adjusted MRD-negativity (CR+) rates (95% CI) were 30.2% (21-39.4) vs 5.3% (0.9-9.8), respectively (OR, 7.67; 95% CI, 3.10-22.72; P <.0001). ORR and TTD favored BPd vs DVd (ORR not significant). Conclusions: This post hoc indirect comparison analysis showed that BPd significantly improved PFS vs DVd (similar HR to BVd vs DVd in D7). Median PFS for the adjusted DVd population was similar to that reported with PVd in D8. These findings suggest that BPd may be a more effective treatment option vs DVd, warranting further studies of belamaf combinations in this population.
BACKGROUND: The resection margins and their prognostic significance are still subject of conflicting opinions. This paper is aimed to update our previous study with a more adequate follow-up, and to evaluate a stratification into risk categories and effectiveness of adjuvant treatment.METHODS: A prospective study, carried out between 2015 and 2018 with the participation of 10 reference hospitals. The primary objective was evaluating local control.RESULTS: Four hundred fifty-four enrolled patients had a minimum follow-up of three years. The previous treatment, fresh specimen evaluation and nearest microscopic margin (mm) on the specimen, were risk factors in the multivariate analysis for local control. Risk classes are delineated for the different oncological outcomes. The prognostic significance of the margins is confirmed; other factors emerge as risk profiles, which would require diversified treatments and follow-up.CONCLUSIONS: Infiltrated margins appear characteristic of a more aggressive disease, sometimes preoperatively identifiable. Adjuvant therapy and collaboration with the pathologist are able to improve the results.
