BACKGROUND:CD19-directed chimeric antigen receptor (CAR) T-cell therapy has become the preferred cellular immunotherapy for relapsed/refractory (r/r) large B-cell lymphoma (LBCL), whereas allogeneic hematopoietic cell transplantation (allo-HCT) remains a potential salvage option. Comparative real-world data between both approaches are limited. PATIENTS AND METHODS:We conducted a retrospective single-center real-world analysis comparing outcomes of allo-HCT and CD19-directed CAR T-cell therapy with axicabtagene ciloleucel (axi-cel). A total of 187 patients with r/r large B-cell lymphoma (r/r LBCL) were included. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included relapse incidence (RI), non-relapse mortality (NRM), and treatment-related toxicities. Propensity score matching (PSM) was performed to adjust for baseline differences. RESULTS:Response rates and relapse incidence were comparable between groups. However, NRM was significantly higher after allo-HCT (12% vs. 36%; P = < .001), mainly driven by infections and graft-versus-host disease. Consequently, axi-cel was associated with superior survival, with 12-month PFS of 50.1% versus 33.8% and OS of 60.5% versus 43.2% (both P < .05). These findings were confirmed in subgroup analyses (≥ 3rd line) and propensity score-matched cohorts. Multivariable analyses identified primary refractoriness and poor performance status as adverse prognostic factors, while treatment modality mainly impacted NRM rather than relapse risk. CONCLUSION:In conclusion, axi-cel provided superior PFS and OS to patients with r/r LBCL compared with allo-HCT, primarily due to lower treatment-related mortality and improved disease control in patients with chemorefractory disease prior to cellular therapy.

Abstract Donor lymphocyte infusions (DLI) are an important strategy for managing relapse after allogeneic hematopoietic stem cell transplantation (allo-HCT), yet data on the impact of surveillance frequency and DLI timing remain limited. We retrospectively analyzed 83 adults with acute leukemia or MDS who received DLI after relapse between 2010 and 2022. Monthly molecular monitoring with donor chimerism and genetic markers enabled classification of preemptive DLI at molecular relapse and therapeutic DLI at overt hematologic relapse. Overall survival (OS) was assessed using Kaplan–Meier estimates and Cox regression. Therapeutic DLI was associated with inferior OS compared with preemptive DLI (HR = 0.15 in multivariable analysis, p < 0.001); median OS was 0.47 years in the therapeutic group, while it was not reached after preemptive DLI. GvHD after DLI was associated with better OS (HR = 0.28), consistent with graft-versus-leukemia effects. A longer interval between allo-HCT and relapse also predicted improved survival (HR = 0.78). Delivering DLI at molecular rather than hematologic relapse improved survival, suggesting that close MRD-based surveillance enables earlier detection, timely immunologic intervention, and may improve post-relapse outcomes.

Myelodysplastic neoplasia (MDS) comprises heterogeneous clonal hematologic disorders characterized by peripheral cytopenia, bone marrow dysplasia, and a risk of leukemic transformation. A hypoplastic variant (MDS-h) shares features with aplastic anemia and responds to immunosuppressive therapy (IST). We report three low-risk MDS-h cases treated with IST and monitored over 9-17 years using serial cytogenetic and molecular analyses. All patients achieved transfusion independence after IST, and two experienced durable, long-term remissions. One patient developed late clonal evolution culminating in secondary acute myeloid leukemia. Molecular follow-up revealed diverse mutational dynamics, including stable and fluctuating clones and delayed mutational emergence, detectable in peripheral blood. These findings suggest that in MDS-h, disease activity is largely driven by immune dysregulation rather than early molecular changes, and that repeated IST can yield sustained remissions. However, accumulating mutations may eventually predict malignant transformation, underscoring the importance of long-term molecular monitoring.

BACKGROUND:Treatment options after PD-1 inhibition for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) remain limited. We investigated whether staggered immune checkpoint inhibition could improve outcomes compared with docetaxel in nivolumab-refractory disease. METHODS:In this randomized phase II trial, adults with platinum-refractory R/M-SCCHN received nivolumab and were randomized at progression to nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (NIVO-IPI) or docetaxel 75 mg/m² every 3 weeks (DOCE) until progression or intolerance. The primary endpoint was objective response rate (ORR) per RECIST 1.1; progression-free survival (PFS), overall survival (OS), and safety were secondary endpoints. PD-L1 expression was assessed in all patients. RESULTS:Among 14 patients in the NIVO-IPI arm and 17 in the DOCE arm, ORR was 0% versus 17.6%, median PFS was 1.97 versus 3.66 months (P = 0.036), and median OS was 3.97 versus 11.9 months (P = 0.356), respectively. Twelve-month OS rates were 28.6% and 44.6%. Outcomes were similar irrespective of PD-L1 status. Treatment-emergent adverse events occurred in 84.6% versus 81.3% of patients, with grade ≥3 events in 38.5% and 68.8%. CONCLUSIONS:NIVO-IPI did not improve efficacy over docetaxel and showed numerically inferior survival, whereas docetaxel was associated with greater toxicity. CLINICAL TRIAL REGISTRATION:EudraCT Nr. 2017-003349-14.

Introduction : Adult acute T-cell lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a rare and aggressive malignancy. Allogeneic hematopoietic stem cell transplantation (allo-HCT) represents a potentially curative option for high-risk or relapsed/refractory (r/r) disease; however, outcomes following relapse after allo-HCT remain poorly defined due to limited real-world data. This retrospective study evaluated post-transplant outcomes, relapse patterns, and salvage strategies in adult T-ALL/LBL patients treated at a single academic center. Methods : We conducted an analysis of 42 adult patients diagnosed and treated with T-ALL/LBL between 2007 and 2025. Survival outcomes, including overall survival (OS), progression-free survival (PFS), relapse-related mortality (RRM), and non-relapse mortality (NRM), were assessed. Kaplan–Meier estimates, Cox proportional hazards models, and competing-risk analyses were applied to evaluate outcomes and prognostic factors following first allo-HCT. Results : Among confirmed T-ALL/LBL patients, 35 (83%) underwent allo-HCT, either in first complete remission (CR1) with high-risk features or in ≥CR2. Median age at transplantation was 32 years. After allo-HCT, median OS was 18.9 months and twelve patients (34%) relapsed. Patients typically relapsed early, with a median time to relapse of 5.3 months. All patients who relapsed post-allo-HCT ultimately died, predominantly from progressive disease. Salvage strategies, including nelarabine-based chemotherapy, donor lymphocyte infusions, daratumumab, experimental agents, or second allo-HCT, resulted in only transient responses. No significant differences in OS were observed between T-ALL and T-LBL or between frontline and salvage allo-HCT. Conclusions : Currently available salvage therapies for T-ALL/LBL patients who relapse after allo-HCT have limited efficacy. This results in fatal outcomes. The findings presented here underscore the urgent need for novel targeted and cellular therapies, such as CAR T-cell based therapies, and support the enrollment of r/r patients into prospective clinical trials.

ABSTRACT Background Allogeneic hematopoietic cell transplantation (alloHCT) remains a curative option for relapsed or refractory (r/r) mantle cell lymphoma (MCL), although its role has shifted in the era of Bruton tyrosine kinase inhibition (BTKi) and chimeric antigen receptor T‐cell (CAR‐T) therapy. Real‐world evidence on long‐term outcomes and salvage strategies after relapse is limited. Methods We performed a retrospective analysis of 29 patients with r/r MCL who underwent alloHCT between 2001 and 2017 using either higher‐intensity or reduced‐intensity conditioning. Outcomes assessed included overall survival (OS), progression‐free survival (PFS), relapse incidence, and non‐relapse mortality (NRM), focusing on relapse timing and management. Conditioning regimens were compared exploratorily. Results With a median follow‐up of 143 months (95% CI: 104–NR), 3‐year OS and PFS were 41% and 34%, respectively. Relapse occurred in 38% of patients, including over one quarter with late (> 12‐month), predominantly localized relapse. Salvage radiotherapy, alone or combined with BTKi, achieved durable disease control in about two‐thirds of patients. Differences between higher‐intensity and reduced‐intensity conditioning were observed but remained exploratory and not statistically conclusive. Conclusion In this real‐world cohort, alloHCT provided sustained disease control for a subset of r/r MCL patients, including late, localized relapse amenable to salvage therapy. As alloHCT is now performed less frequently, such datasets are critical for decision‐making in patients after CAR‐T ineligibility or failure, especially where CAR‐T access is limited. These findings support a continued, selective role for alloHCT in the modern treatment landscape and emphasize the need for real‐world evidence to guide patient selection and sequencing in the CAR‐T era. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

BackgroundRelapse is the main cause of treatment failure after allogeneic hematopoietic cell transplantation (allo-HCT). Therapeutic donor lymphocyte infusion (DLI) and second allo-HCT are common post-relapse options, but comparative evidence from the time of relapse is limited.MethodsWe retrospectively analyzed 85 adults with acute leukemia or myelodysplastic syndromes (MDS) who received therapeutic DLI or a second allo-HCT after relapse (2010–2022). DLI required hematologic or clinical relapse. Overall survival (OS) was assessed using Kaplan–Meier analysis, Cox regression, and propensity score matching (PSM). Competing risks models evaluated relapse-related mortality (RRM) and non-relapse mortality (NRM).Results60 patients received DLI and 25 underwent a second allo-HCT. No significant difference in OS was observed between groups (median OS 0.92 vs. 0.61 years, p=0.295). DLI showed higher RRM, while second allo-HCT showed a trend toward higher NRM. In the matched cohort (n = 36), OS remained numerically longer after second allo-HCT without significance.ConclusionOS did not differ between second allo-HCT and therapeutic DLI. Treatment should be individualized, and larger multicenter studies are needed to refine patient selection.

While allogeneic stem cell transplantation (alloSCT) remains the only curative option for patients with relapsed T-cell lymphoma, its place in the treatment algorithm of aggressive B-cell lymphoma is changing. This multicentre, prospective, investigator-initiated trial investigated the efficacy and toxicity of a myeloablative conditioning regimen comprising fludarabine, thiotepa, and cyclophosphamide (FTC) prior to alloSCT in patients with relapsed/refractory (r/r) aggressive B-cell or T-cell lymphoma. Among 60 patients, PFS at one and two years was 40% (95% CI 28-52) and 36% (95% CI 24-49), OS was 43% (95% CI 31-56) and 37% (95% CI 25-50), respectively, without significant differences between 42 patients with B-cell and 18 patients with T-cell lymphoma. The primary endpoint of the study defined as 1-year PFS of 50% was not met. The cumulative incidence of progression/relapse at two years was 34% (95% CI 19-49) for B- and 11% (95% CI 0-26) for T-cell patients. Cumulative incidence of NRM was 25% (95% CI 14-36) at day 100 and 35% (95% CI 23-47) at one year. Twelve patients who had failed CAR T-cell therapy (CART) had outcomes comparable to patients without prior CART. In T-cell lymphoma, relapse after alloSCT was notably low, reflecting a strong graft-versus-lymphomaeffect. In B-cell lymphomas, our data suggest that alloSCT can be effective after CART failure, with more than one-third of patients being in remission after two years. These findings support the continued use of alloSCT in patients with aggressive lymphomas. Substantial NRM observed after FTC calls for the continued search of better tolerated conditioning regimens.

BACKGROUND:Consolidation therapy for primary CNS lymphoma (PCNSL) includes high-dose chemotherapy with autologous stem-cell transplantation (HCT-ASCT), yet its efficacy compared with non-myeloablative chemoimmunotherapy remains uncertain. This study aimed to provide randomised comparative evidence on the efficacy and safety of thiotepa-based HCT-ASCT versus non-myeloablative R-DeVIC consolidation after uniform MATRix induction in newly diagnosed PCNSL. METHODS:This open-label, randomised, phase 3 trial was conducted across 56 university and academic non-university hospitals with established transplantation facilities in five European countries. Eligible for inclusion were untreated, immunocompetent patients with B-cell PCNSL, aged 18-65 years regardless of Eastern Cooperative Oncology Group (ECOG) performance status, or 66-70 years with ECOG performance status 0-2. Pretreatment corticosteroids were permitted. Exclusion criteria included lymphoma manifestation outside the CNS, and congenital or acquired immunodeficiency. Patients received four cycles of MATRix induction (comprising rituximab, high-dose cytarabine, and thiotepa, in addition to high-dose methotrexate). Patients reaching at least partial response were randomly assigned (1:1) to two cycles of R-DeVIC (rituximab plus dexamethasone, etoposide, ifosfamide, and carboplatin) or HCT-ASCT with carmustine and thiotepa. The primary endpoint was progression-free survival, assessed in the full analysis set (excluding patients with major violations of entry criteria). The safety analysis set contained all randomised patients who initiated therapy. This study is registered with ClinicalTrials.gov (NCT02531841) and the EU Clinical Trials Register (EudraCT number 2012-000620-17). The study is completed. FINDINGS:Between July 16, 2014, and Aug 31, 2019, 368 patients were enrolled. 346 (94%) patients started induction treatment, and 230 were randomly assigned; 229 patients were analysed (R-DeVIC group, n=115; HCT-ASCT group, n=114). After a median follow-up of 45·3 months, 3-year progression-free survival was significantly superior in the HCT-ASCT group (hazard ratio 0·43 [95% CI 0·27-0·68]; p=0·0003). The 3-year progression-free survival was 78% (95% CI 69-85) in the HCT-ASCT group compared with 51% (41-60) in the R-DeVIC group. The mean number of adverse events per patient was 9·3 (SD 4·4) in the R-DeVIC group and 14·6 (5·8) in the HCT-ASCT group. Fatal serious adverse events following consolidation treatment occurred in two patients in the R-DeVIC group (both acute myeloid leukaemia) and in five patients in the HCT-ASCT group (infections and infestations [n=4], pulmonary embolism [n=1]); all of these events apart from the pulmonary embolism were judged to be possibly related to treatment. INTERPRETATION:In the largest randomised trial in untreated PCNSL to date, HCT-ASCT significantly improved progression-free and overall survival compared with non-myeloablative consolidation in patients who had completed induction treatment, establishing it as the preferred consolidation strategy in fit patients. FUNDING:German Federal Ministry of Research, Technology and Space; Swiss Cancer Research Foundation; and Riemser Pharma.

Background Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for acute leukemia and myelodysplastic syndromes (MDS), yet long-term survival remains limited. Currently established prognostic scores differ in complexity and predictive accuracy. We aimed to systematically benchmark conventional prognostic models and develop a simplified, data-driven score to improve overall survival (OS) prediction after allo-HCT. Methods We retrospectively analyzed 561 adult allo-HCT recipients treated at our institution between 2010 and 2024. Of these, 421 patients with complete data on EBMT Score, HCT-CI Score, EASIX Score, log₂EASIX, ECOG Score, and OS formed the primary analysis cohort. We first benchmarked existing prognostic scores using Harrell's concordance index (C-index). A simplified model was then developed in an expanded cohort (n = 525; 421 patients from 2010–2022 plus 104 from 2023–07/2024) using forward variable selection in a Cox proportional hazards framework. All analyses were performed using reproducible Python code. Results Among conventional scores, the EBMT Score performed best (C-index 0.586), while HCT-CI, EASIX, log₂EASIX, and ECOG showed lower discrimination (C-index 0.445–0.550). The final model included age at transplant (in years) and disease stage, categorized according to the original EBMT Score definitions, and weighted by Cox regression coefficients. The resulting simplified Age and Stage (SAS) Score was calculated as: SAS Score=Age+9 × (Disease Stage) Internal validation using 1000-fold bootstrapping showed that the SAS Score significantly outperformed the original EBMT Score, with an absolute C-index improvement of +0.045 (95% CI: 0.0131–0.0787). Likelihood ratio testing also confirmed superior model fit (LR = 20.06; p = 7.5×10⁻⁶). In addition, SAS Score demonstrated better calibration (intercept: 0.026 vs. 0.195; slope: 0.533 vs. 0.302) and comparable overall prediction error (Brier score at 1 year: 0.280 vs. 0.257). In comparison, a logistic regression using the same variables achieved similar discrimination (C-index 0.613, AUC: 0.613), while a random forest model showed signs of overfitting (C-index 0.865, AUC: 0.497). Stratification by SAS Score tertiles (low: ≤58.1, intermediate: 58.2–71.8, high: ≥71.9) revealed a significant OS difference between high- and low-risk groups (log-rank p < 0.00001), supporting the model's discriminative capacity. Conclusion We developed a transparent, statistically robust, and clinically applicable prognostic score using only two variables. Compared to existing models, the SAS Score improves OS prediction and enables effective risk stratification. It may support pre-transplant decision-making and warrants prospective validation in multicenter settings.

Treatment of relapsed or refractory aggressive B-cell lymphoma (aNHL) is still an unmet medical need. Platinum-containing salvage immunotherapies achieve remission rates of 40-60%. The phase I/II DSHNHL-R6 trial sought to investigate feasibility, safety and efficacy of R-DHAP plus lenalidomide in patients with first or subsequent relapse of aNHL. 33 patients were enrolled in the trial and could be analyzed (ITT). Lenalidomide dose was stepwise increased if no dose-limiting toxicities were observed. Maximum tolerated dose (MTD) for lenalidomide in combination with R-DHAP was 15 mg administered on days 1-7 of each cycle. The overall response rates (ORR; defined as complete, unconfirmed complete or partial remission; using the revised response criteria by CT) and complete response rates (CR) rates were 60.6% and 27.3% for the ITT-population and 81.3% and 50.0% in the patients treated as per protocol (PP). With a median follow-up of 13.9 months, the median OS was 21.2 months and PFS for the ITT and PP-population were 10.7 and 18.9 months respectively. No treatment related deaths were observed. Haematologic adverse events (77% grade 3-4) were common. Combining Lenalidomide with R-DHAP is an effective salvage therapy for patients with aNHL. Prolonged use of lenalidomide lead to more toxicities. (registered at www.clinicaltrialsregister.eu ; EudraCT number: 2009-010824-25; Start Date: 2010-04-12).

Background: CPX-351 has emerged as a preferred induction therapy for patients (pts.) with acute myeloid leukemia (AML) with myelodysplasia-related changes and therapy-related AML, demonstrating superior outcomes compared to standard 7+3. Initial response assessment in clinical routine is done by bone marrow cytomorphology after 1st induction. However, genetic mutations and cytogenetic abnormalities significantly impact remission rates and may have predictive value. Molecular profiling post-induction is essential for refining prognosis, guide consolidation strategies, and inform the potential for allogeneic stem cell transplantation (allo-tx). Aim: This study aims to describe the molecular response of pts. with AML to induction with CPX-351 and its impact on prognosis. We assess the concise genetic background of the disease with a focus on molecular aberrations and pursue the response of these mutations to treatment. Furthermore, we correlate to survival data. Methods: We screened patient charts for induction with CPX-351 at our tertiary medical center. Pts. were included in the study if they had obtained initial NGS workup with a panel of up to 53 genes and at least one more NGS analysis after induction and excluded if either of those were missing. Treatment, response and survival data were retrieved by chart review. Molecular data was provided by our genetical laboratory INDIGHO. For molecular response, we defined complete molecular remission (CMR) as variant allele frequency (VAF) <1%, very good partial MR (VGPMR) as VAF <5%, partial MR as reduction of VAF >10% but not reaching residual VAF <5%, idem as VAF reduction <10% or increase <5%, and progression (PROGR) as VAF increase >5%. Fisher's exact test and the method of Kaplan and Meier were used to compare groups and perform survival analyses. Results: A total of 73 consecutive pts. with AML treated with CPX-351 induction were identified at our center between 03/2019 and 06/2025. Of those, 51 were evaluable with at least one NGS analysis before and after induction. The median age is 64 years (range 41-75), there are 30 males and 21 females. 45 pts. have AML-MR, 5 myeloid neoplasia post cytotoxic therapy and 1 AML with MECOM rearrangement per WHO 2022. 39 pts. received allo-tx. Conventional response assessment by cytomorphology resulted in 39 CR (78%), 4 PR (8%), 7 (14%) refractory and 1 pt. not evaluable due to dry tap. Molecular response assessment stratified by the worst responding gene mutation per pt. resulted in 8 CMR, 4 VGPMR, 17 PMR, 3 idem, 19 PROGR. Notably, most pts. with molecular PROGR were cytomorphologically defined as CR (15/18 evaluable pts., 83.3%). A total of 159 gene mutations in 33 genes were detected. The most frequently mutated genes were DNTM3A (n=16), RUNX1 (16), TET2 (13), and TP53 (12). Of the 159 mutations, 38% achieved a CMR, 12% a VGPMR, 28% a PMR after induction. 6 % stayed idem and 16% PROGR. For pts. achieving CMR or VGPMR after 1st induction, the alive:death ratio is 11:1, while the ratio is 22:17 for pts. with PMR, idem, or PROGR (p=0.0373). Comparing overall survival (OS), pts. achieving CMR or VGPMR demonstrated a trend towards longer OS than pts. in morphological CR (median OS not reached vs. 28 months, p=0.055), with an encouraging signal in the allo-tx subgroup as well (median OS not reached vs. 53 months, p=0.076). Conclusions: Our data demonstrates that molecular response assessment is feasible in a real-world setting after AML induction therapy with CPX-351. CPX-351 induces CMR or VGPMR in 24% and PMR in 33%, resulting in molecular responses in 57% of pts. While conventional cytomorphology demonstrates a CR in 78% of pts., molecular analysis improves detection of residual disease. Pts. achieving CMR or VGPMR after the 1st induction experienced a significantly lower mortality rate than those with worse molecular responses (p=0.0373). Furthermore, they show a trend to superior survival for the whole cohort (p=0.055) and for the allo-tx subgroup (p=0.076) than pts. in morphological CR. This analysis is limited due to the sample size and short follow-up. Taken together, CPX-351 induces a high rate of molecular remissions in pts. with AML. Molecular remission status refines prognostic accuracy and should be considered for disease assessment and treatment guidance. Additional analyses including cytogenetics and molecular response during subsequent course of treatment and expansion of the cohort are under investigation and will be reported.

Introduction The introduction of B-cell maturation antigen (BCMA) directed chimeric antigen receptor-T (CAR-T) cell therapies have revolutionized the treatment landscape of relapsed/refractory (r/r) multiple myeloma (MM). Currently, two CAR-T products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are approved for r/r MM and demonstrated remarkable efficacy in the pivotal trials. However, data on the efficacy and safety of these therapies in older patients - who often have more comorbidities and are frequently underrepresented in approval studies - remain limited. Real-world evidence is needed to complement clinical trial findings and report clinical practice and outcomes. We sought to fill this gap by evaluating the efficacy and toxicity profiles of patients aged 70 and older compared to their younger counterparts in a real-world setting. Methods We conducted a multicenter retrospective analysis including 136 relapsed/refractory MM pts without CNS manifestation undergoing CAR-T cell treatment with ide-cel between March 2022 and May 2024 at seven tertiary german centers. Patients were grouped by age at CAR-T infusion ((<70 vs. ≥70 years (yrs)). Subsequently, descriptive and survival analyses, including propensity score matching (nearest neighbor 1:1 matching with R-ISS stage, number of therapy lines, triple- and penta-class refractoriness, and remission status as co-variates), were performed to compare outcomes between both age groups. Results We identified 91 patients aged <70 and 45 patients aged ≥70 yrs. The median age was 61 yrs (range: 36-69 yrs) and 72 yrs (range: 70-82 yrs) at CAR-T infusion, respectively. Thirteen (9.6%) patients were aged ≥75 yrs. Both groups had similar proportions for ECOG score 0-2 (74.4% vs. 84.4%, p=0.27), R-ISS stage III at diagnosis (28.6% vs. 42.2%, p=0.38), high-risk cytogenetics (51.8% vs. 35.9%, p=0.12), median time from first diagnosis to CAR-T (6.9 vs. 8.0 years, p=0.26), penta-refractory status (51.6% vs. 62.2%, p=0.36), prior BCMA-directed therapy (14.4% vs. 15.6%, p=1.0), and prior autologous stem cell transplantation (93.4% vs. 86.7%, p=0.21). Both groups had a median of five prior treatment lines (p=0.49). There were no significant differences in disease status at CAR-T infusion regarding serologic CR and VGPR/PR (7.7% vs. 11.1% and 25.3% vs. 31.1%, both p=0.31). Both groups had a median of one bridging therapy line (p=0.65). Notably, extramedullary disease at CAR-T was more frequent in patients <70 yrs compared to those ≥70 yrs (37.6% vs. 14.0%, p=0.007). Cytokine-release syndrome (CRS) grade 3-4 occurred in 7.7% of the younger group and 4.4% of the older group (p=0.71). For all grades of ICANS, there was a higher proportion in patients ≥70 yrs (24.4% vs. 6.6%, p=0.005), but no difference for ICANS grade 3-4 (0% vs. 2.2%, p=1.0). Tocilizumab usage was similar across both groups (p=0.16), as were infections within 30 days post-CAR-T (p=0.19), and lowest values of neutrophils (p=0.12), platelets (p=0.72), hemoglobin (p=0.95), and IgG (p=0.88). Overall response rates considering CR/VGPR/PR were comparable for both age groups (87.8% vs. 92.7%; p=0.274). With a median follow-up of 8.1 months, median progression-free survival (PFS) was 9.2 months (95%-CI: 6.7-14.1) for the younger group and 9.6 months (95%-CI: 6.9-NR) for the older group (p=0.39), with 1-year PFS rates of 42.9% and 48.7%, respectively. Median overall survival (OS) was not reached; 1-year OS was 67.1% and 66.8% (p=0.95). Additionally, no significant differences were noted in the cumulative incidence of 1-year non-relapse mortality (p=0.17) and cumulative relapse incidence (p=0.08) between the age groups. These results were consistent in the propensity score-matched cohort of 80 patients. In a multivariate regression analysis considering age groups, number of treatment lines, and disease status prior to CAR-Ts as covariates, only extramedullary disease at CAR-T was associated with decreased PFS (HR=1.96, 95%CI: 1.11-3.48, p=0.021). Conclusions With the paucity of long-term data, our real-world analysis provides additional support that CAR-T cell therapy is feasible and effective in patients with r/r MM aged 70 yrs or older, demonstrating outcomes and toxicities comparable to those observed in younger patients. Therefore, CAR-T cell therapy should not be withheld for eligible patients above 70 yrs with r/r MM.

Allogeneic stem cell transplantation (alloSCT) represents a curative option for patients with relapsed/refractory (r/r) aggressive lymphomas. We compared outcomes of alloSCT in r/r PTCL and r/r DLBCL pts (n = 150) who underwent identical myeloablative conditioning chemotherapy, GvHD prophylaxis, and relapse management. 5-year PFS and OS were significantly superior in PTCL compared to DLBCL (56% vs. 24%; 56% vs. 28%; p ≤ 0.005). A landmark analysis (day≥ +100 post-alloSCT) markedly favored outcomes in PTCL vs. DLBCL: 5-year PFS and OS of 76% vs. 30% and 76% and 35%, respectively (p ≤ 0.003). Non-relapse mortality was comparable (35% PTCL vs. 34% DLBCL, p = 0.894), whereas post-alloSCT relapse mortality was significantly higher in DLBCL (36% vs. 10%, p = 0.0007). The occurence of limited chronic GvHD did not improve outcomes in DLBCL, whereas extensive chronic GvHD was a negative risk factor for both (HR 2.09 and 2.80, p ≤ 0.006). In conclusion, we gained evidence for strong graft-versus-lymphoma activity against PTCL but not DLBCL.

ATOS is a prospective observational study evaluating the outcome of patients receiving anti-human T-lymphocyte immunoglobulin (ATLG) in unrelated donor transplantation. Primary endpoint was severe GvHD and relapse-free survival (SGRFS). GvHD prophylaxis consisted of ATLG and CSA/ MTX or MMF. Outcome was compared to the ATLG arm of our prospective randomized phase III multicenter trial trial (RCT) [1, 2]. 165 patients, median age 54 (18; 77) years, with haematological malignancies with early (45.5%), intermediate (17.6%), and advanced (37.0%) disease were included. ATLG dose differed between centers according to local practise (median total ATLG dose of 46 (IQR 32–60, range 15–91) mg/kg). Median follow-up was 70 months. Estimated probabilities at 5 years follow up were for SGRFS 0.27, OS 0.52, DFS 0.43, NRM 0.23, relapse 0.34, acute GvhD °III/IV 0.13, severe chronic GvHD 0.27. OS rates differed dependent on disease status. An effect of the given ATLG dose could not be separated from potential center effects. Despite higher age and more advanced disease in ATOS, outcome was similar to the ATLG arm of our RCT. This long-term, multicenter, experience in routine clinical practice confirms the GvHD-protective effect of ATLG without compromising relapse and non-relapse mortality rates. Clinical Trial Registry: German clinical trials register DRKS00004581.

Background: Bacterial infection ranks amongst the most common causes of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT). Although ciprofloxacin (CIP) prophylaxis is recommended, information on serum levels and clinical course is lacking.Aim: To investigate relationships between CIP level and failure of prophylaxis, particularly in terms of whether different pharmacokinetic (PK) indices [area under the concentration -time curve (AUC(0-24h)) vs single time samples] correlate differently with the outcome.Methods: This prospective observational monocentric study was conducted at a 1500-bed teaching hospital (March 2018 -March 2019), including 63 adult patients with alloHSCT receiving CIP prophylaxis. Blood samples were drawn at three sampling times (1, 6 and 12 h post-administration), twice per week, and measured via high performance liquid chromatography. The onset of febrile episodes (FEBs) indicated suspected failure of CIP prophylaxis. Positive blood cultures [bloodstream infection (BSI)] indicated confirmed failure of prophylaxis.Findings: Seven of 63 patients died without significant differences in their average CIP levels compared with survivors, with patients experiencing FEBs (54/63) displaying a 13% [95% confidence interval (CI) 4-22%] lower probability of survival. In total, 225 sets of three values (triplets) were obtained from 58 primary CIP episodes. Triplets preceding BSI with Gram-negative bacteria (GNB-BSI) showed lower AUC(0-24h) on average, but similar single time sample indices. An AUC(0-24h) of <= 21.61 mgh/L resulted in four-fold higher odds of GNB-BSI (adjusted odds ratio 3.96, 95% CI 1.21-13.00). These results were independent of the administration route, patient demographics or sampling protocol deviations, indi-cating reduced CIP exposure upon GNB-BSI events.Conclusion: Monitoring CIP levels, using multiple sampling times, may be useful to reduce alloHSCT-associated bacterial infections. Further analysis is needed to investigate causality.2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.