The randomized phase II SAKK 35/14 trial, conducted by the Swiss Group for Clinical Cancer Research (SAKK) and the Nordic Lymphoma Group (NLG), compared efficacy and safety of rituximab (375 mg/m2 intravenously for 4 weeks followed by maintenance every 2 months for 24 months) plus placebo (arm A) versus the same schedule of rituximab plus ibrutinib (560 mg daily for 24 months, arm B) in patients with advanced follicular lymphoma in need of systemic therapy. The primary end-point, complete remission (CR) rate at 24 months, was 36% in arm A and 40% in arm B, with no statistically significant difference. Three-year progression-free survival (PFS) was 36% in arm A and 45% in arm B, with a hazard ratio of 0.64 (p = 0.057). Three-year overall survival was about 96% in both arms. A higher percentage of patients in arm B experienced grade ≥3 adverse events, but they were manageable. No toxic deaths were observed. Although the primary end-point (CR rate at 24 months) was not met, a trend towards improved PFS with ibrutinib plus rituximab observed at the prespecified significance level of 0.1 may indicate a potential clinical benefit.

Peripheral T-cell lymphomas (PTCLs) are a rare, heterogeneous group of hematological malignancies with extremely poor prognosis for nearly all subtypes. FDG-PET using specific radiomics indexes have showed to be a possible tool for prognostication, treatment response assessment and to extract quantitative features that correlate with the disease's biological characteristics. However, its usefulness in routine clinical practice for PTCLs is still challenging due to the various subtypes, heterogeneity, and the absence of large prospective trials that include FDG-PET assessment. To address this question, we conducted PET assessment as an ancillary sub-study of the prospective real-world T-Cell Project 2.0 (NCT03964480).Patients and methods: 138 PTCLs patients from 8 international centers with available PET0 AND/OR a EOT-PET were enrolled in this study. For the further analysis were confirmed eligible 104 patients (PTCL-NOS 35, AITL 17, ALCL ALKneg 19, ALKpos 9, NKTCL 13, ATLL 2, others 9). Anonymized scans underwent a central review on WIDEN platform by a pool of nuclear medicine physicians. Tumor segmentation was performed at baseline with a percentage threshold of SUVmax of 41% in each lesion. Quantitative metrics including SUVmax, SUVpeak, total lesion glycolysis (TLG) and MTV were defined for each lesion. TMTV and TTLG were defined as the sum of MTV/TLG through all the lesion while SUVmax and SUVpeak were identified in the lesion with the highest uptake at baseline. EOT-PET were analyzed using Lugano classification with the 5-point Deauville scale.Overall survival (OS) and progression free survival (PFS) were estimated by Kalan-Meier method and the prognostic value was assessed in univariate analysis using log-rank test and estimating the effect as hazard ratio (HR), from Cox PH regression model. All reported p-value were two-sided.Results: Median follow-up time was 39 months (95%CI 32-45). OS and PFS at 3 years were 55 vs 46%, respectively. Median TMTV was 98 ml (5%-95% 3-1213). A TMTV of 200 ml was chosen as threshold between high and low risk group for OS and PFS. The 3-yr PFS for TMTV41% < 230 was 56% vs 31% for >230 (0.020), TMTV41% <130 w/o SL was 56% vs 36% for >130 and TMTV41% <130 w/o SL (p=0.020) and TMTV41% < 130 w/o SL and diff. spleen was 62% vs 39% (p=0.010). In univariate analysis, age>60 yo (p=0.001), LDH>UNL (p=0.014), PS>1 (p=0.008), Hb<12g/dL (p 0.042), albumin<3.5g/dL (p=0.01), PLT<200x109/L (p=0.047), ALC<1x109/L (p=0.031), PIT intermediate (p=0.002) and high (p<0.001), PMR/PMD (p<0.001), DS4-5 (p<0.001), TMTV41%>200ml (p<0.01) were correlated with lower OS. Adverse prognostic features were the same for PFS, except albumin<3.5 g/dL (p=0.06). A DS4-5 in EoT PET demonstrated also to have a strong response assessment value with HR= 4.93 (95%CI 2.40-10.1 in PFS and HR= 3.22 (95%CI 1.48-7.00) in OS. The prognostic value for baseline TMTV was reinforced when combined to DS EOT. The 3-yr OS for DS 1-3&TMTV41%<200 ml vs DS 1-3 &TMTV41% >200 ml vs DS 4-5 was 89%, 56% and 41% (p<0.001), respectively. At the same time timepoints PFS was 85%, 50% and 21% (p<0,001), respectively. Analysis by subtypes delineated a robust association between histological variants and metabolic activity, with AITL displaying the highest median TMTV 41% of 486.2 ml compared with 141.6 ml for PTCL NOS, 188.8 ml for ALK +, 88 ml ALK – and 77.0 for other rare PTCL subtypes (p=0.033). Besides this empirical observation, there was no statistically significant difference between histological subtypes and metabolic activity (p=0.073).Conclusion: Our data confirm that TMTV41% appears to be a robust biomarker for different histological PTCLs subtypes for development the first-line PET-adapted approaches in PTCL. The identified threshold of TMTV41% >230ml effectively stratifies patients into high and low-risk groups and suits as a more promising tool. Moreover, high TMTV has been associated with poor outcomes independently of clinical prognostic factors. Different segmentation methods are being analysed (SUV4). Further analyses is needed to fully understand how the metabolic activity may vary between different PTCLs subtypes.

INTRODUCTION: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare disease, with unique diagnostic challenges and often dismal outcome. There are no widely accepted treatment guidelines available. Lymphoma-like regimens with or without autologous or allogenic transplantation were the cornerstone of most therapeutic concepts. A few years ago, the CD123-directed immunoconjugate tagraxofusp emerged as a new valuable treatment option. The goal of our research was to collect available data on BPDCN-patients treated at large centres in Switzerland and worldwide and to draw conclusions regarding the incidence, clinical presentation, prognostic factors and therapeutic strategies. METHODS: We collected data from BPDCN patients from leading Swiss haemato-oncology centres from 2005 to 2022. Furthermore, we reviewed and analysed the published literature (cohorts and case reports in peer-reviewed journals) from 1997 to 2020 (structured review of the literature). RESULTS: We identified 115 international publications including 600 patients from all over the world. Most of them had very small sample sizes (only ten papers with more than ten patients) and all but one were retrospective or observational respectively. Most included patients were Europeans (n = 385, 64%) and Asians (n = 120, 20%), followed by Americans (n = 90, 15%) and patients from Australia/New Zealand (n = 3) and Africa (n = 2). BPDCN was more common in men with a predominance of 3:1. The median age (n = 414) at diagnosis was 66.5 years ranging from one month to 103 years. Newly diagnosed women were significantly younger than men (median: 62 vs 67 years, mean: 53.4 vs 59.3 years, p = 0.027) and less often had bone marrow infiltration and affected lymph nodes. Upfront allogenic transplantation as well as ALL regimens performed best, with response to first-line therapy clearly associated with better overall survival. The Swiss cohort contained 26 patients (23 males and 3 females) over 18 years (2005–2022). The median age at diagnosis was 68.5 years (range: 20–83). Ten patients underwent upfront stem cell transplantation (seven allogenic and three autologous), at least trending towards a better overall survival than other therapies. With a follow-up of 8 years, the median overall survival was 1.2 years. Eight patients in this cohort were treated with tagraxofusp, which became available in 2020 and was approved by Swissmedic in 2023. CONCLUSIONS: Our study confirms that BPDCN is a very rare and difficult-to-treat disease. Underdiagnosis and underreporting in the literature pose further challenges. Symptoms at presentation seem to differ slightly between sexes and reaching a complete remission after first-line treatment remains crucial for a prolonged overall survival. Effective treatment protocols in first line include transplantation regimens (mainly allogenic, potentially also autologous) as well as ALL protocols. In order to understand the significance of tagraxofusp as a bridge to transplant or as a continuous monotherapy in elderly patients, further evaluation with longer follow-up periods is required. In general, analysis of the Swiss patients confirmed the results from the worldwide cohort.

PURPOSE:Positron emission tomography (PET)-guided therapy with 4-6 cycles of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) is highly effective in younger patients with advanced-stage classic Hodgkin lymphoma (AS-cHL). We report feasibility and efficacy of PET-guided BrECADD as first-line treatment in older patients with AS-cHL. PATIENTS AND METHODS:Patients with AS-cHL aged 61-75 years were enrolled in a phase II single-arm cohort of the HD21 trial (ClinicalTrials.gov identifier: NCT02661503). Patients with negative PET/computed tomography after 2×BrECADD (PET2) received a total of 4×BrECADD, while PET2-positive patients received 6×BrECADD. The primary end point was the centrally reviewed complete remission (CR) rate after the end of chemotherapy (EOC). Secondary end points included feasibility, adverse events, treatment-related morbidity (TRMB), progression-free survival (PFS), overall survival (OS), and health-related quality of life (HRQoL). RESULTS:Between June 2020 and April 2023, 85 patients were enrolled, of whom 83 with a median age of 67 years (range, 61-75) were analyzed in the intention-to-treat cohort. Most prevalent ≥grade 3 toxicities included leukopenia (n = 80 [96%]), thrombocytopenia (n = 71 [86%]), anemia (n = 57 [69%]), and febrile neutropenia (n = 46 [55%]). Forty-eight (60%) of 80 patients with centrally reviewed PET2 were scheduled for 4×BrECADD and 32 (40%) for 6×BrECADD. Of these, 71 patients (89%) received the target number of cycles. Sixty-eight patients (82%; 95% CI, 72 to 90) achieved CR at EOC. PFS and OS estimates at 2 years were 91.5% (95% CI, 85 to 98) and 90.8% (95% CI, 84 to 98), respectively. No death was attributed to study treatment. Initially, impaired HRQoL scores improved during follow up and on average reached population reference values. CONCLUSION:PET-guided BrECADD in older patients is feasible and effective. With a PFS rate on par with that of younger patients, short duration, and limited anthracycline exposure, BrECADD is a valuable treatment option also for older patients with AS-cHL.

BACKGROUND:While formalized treatment recommendations for non-small cell lung cancer (NSCLC) by a multidisciplinary tumor board (MDT) have been associated with improved patient care and potentially improved survival, there is no data on the prognostic impact of individual adherence to initial MDT treatment recommendations in patients (pts) with stage III NSCLC. PATIENTS AND METHODS:Multimodal treatment data for stage III NSCLC pts between 2014 and 2020 were collected from 3 Swiss referral centers. All pts underwent MDT before treatment. MDT-adherence was defined as implementation of the initially recommended treatment modalities and their sequence. Event-free survival (EFS) (primary endpoint) and overall survival (OS) were subjected to Kaplan-Meier analysis, MDT adherence to multivariable Cox regression analysis. RESULTS:Adherence to initial MDT recommendations was found in 385/547 (70.4%) eligible pts. Treatment de-escalation was the prominent feature in 109/162 (67.3%) non MDT-adherent pts, resulting in 89/547 (16.3%) pts receiving non-curative treatment. Pts ≥ 65 years of age had an increased risk for MDT nonadherence (32.8% vs. 23.0%, P = .02), as had pts with a higher tumor stage (19.8% for IIIA, 38.5% for IIIB, 43.3% for IIIC, P < .001) and frail (ECOG ≥ 2) pts (53.7% vs. 22.8%, P < .001). Median EFS was higher in MDT-adherent pts (11.9 months vs. 8.6 months (mo), P = 0.003), as was OS (20.3 mo vs. 9.4 mo, P < .001). CONCLUSIONS:One third of stage III NSCLC pts is unable to adhere to initial MDT recommendations even in tertiary referral centers. Nonadherence was associated with worse outcome. Treatment strategies for vulnerable pts should critically be reviewed.

ABSTRACT:The Swiss Group for Clinical Cancer Research (SAKK) and the Nordic Lymphoma Group conducted the SAKK 35/10 randomized phase 2 trial to compare rituximab (R) alone vs R plus lenalidomide (L) as initial treatment for follicular lymphoma (FL). Patients with grade 1 to 3A FL, requiring systemic therapy, were randomized to either R (n = 77; 375 mg/m2 IV × 1, weeks 1-4) or rituximab-lenalidomide (RL) (n = 77; R on the same schedule and L at 15 mg daily continuously). Responders (evaluated at 10 weeks) repeated R during weeks 12 to 15 with or without L (for a total of 18 weeks). Both arms had 47% of patients with a poor risk score on the FL International Prognostic Index. The primary end point, complete response (CR)/CR unconfirmed rates at 6 months, was superior with the combination, and after a median follow-up of 9.5 years, this has translated into a longer duration of response (median, not reached vs 3.2 years; hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.21-0.86; P = .014), progression-free survival (9.3 vs 2.3 years; HR, 0.57; 95% CI: 0.37-0.89; P = .0128), and time to next treatment (median, not reached vs 2.1 years; HR, 0.43; 95% CI, 0.27-0.67; P < .001). Over 60% of RL responders remained in first CR at 10 years. Overall survival was similar in both arms (77% vs 78% at 10 years; P = .881). Toxicity was more common with RL but manageable. The SAKK 35/10 trial's long-term results confirmed a durable benefit of a short-term chemotherapy-free first-line RL regimen in symptomatic FL. This trial was registered at www.clinicaltrials.gov as #NCT0137605.

Since the publication of the first Swiss recommendations on systemic light-chain amyloidosis in 2020, treatment strategies have evolved. As a result of the third joint meeting of the Swiss Amyloidosis Network, a multidisciplinary and multicentre Swiss clinical consortium, in 2024, recommendations for the treatment of light-chain amyloidosis were updated. They discuss the role of the new standard first-line protocol Daratumumab, Cyclophosphamide, Bortezomib, Dexamethasone (Dara-CyBorD), the timing and indication of high-dose treatment and potential second-line strategies as well as emerging treatment options, with a special focus on multidisciplinary supportive care measures. The update represents a synopsis of current evidence and expert consensus and intends to provide general treatment guidance tailored to the Swiss healthcare system. Nonetheless, treatment decisions should always be personalised and involve a multidisciplinary approach. This update replaces the previous “therapeutic recommendations” while the previous “diagnostic recommendations” remain valid.

B ackground: PET-adapted therapy with four or six cycles of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (4-6x BrECADD) is highly effective in patients up to 60 years with Advanced-stage classic Hodgkin lymphoma (AS-cHL; Borchmann P et al. The Lancet 2024). However, highly effective treatments are still an unmet need for older patients with AS-cHL. Here we report feasibility, safety and efficacy of PET-guided BrECADD as first-line treatment of AS-cHL in patients 61-75 years of age, who have been treated within the GHSG HD21 study. Methods: We designed a phase II single-arm cohort within the international HD21 trial (NCT02661503) for patients with AS-cHL aged 61-75 years to receive BrECADD. PET/CT restaging was done after 2x BrECADD (PET2). If PET2 was negative (i.e. Deauville score (DS) 1-3), treatment was reduced to a total of 4x BrECADD, while patients with PET2-positive lymphoma residuals (DS >3) were scheduled to receive 6x BrECADD. Consolidation radiotherapy was recommended for PET-positive residuals after central review of PET/CT at end of chemotherapy (EOT). The primary endpoint for this cohort was the complete response (CR) rate after EOT according to central review. Secondary endpoints included adverse events, treatment-related morbidity (TRMB, defined as the occurrence of relevant acute non-hematologic organ toxicity ≥ grade 3 or relevant hematologic toxicity grade 4), feasibility, progression-free survival (PFS) and overall survival (OS). Results: Between June 2020 and April 2023, 85 patients with AS-cHL were enrolled in the HD21 Older Cohort. Following disconfirmation of cHL by expert pathology review in one patient, the final ITT population consisted of 84 patients. Median age was 66.5 years (range: 61-75, IQR 63-70) and a majority had Eastern Cooperative Oncology Group (ECOG) performance status ≥1 (52%, range 0-2), stage IV (54%), B-symptoms (75%) and an IPS ≥3 (73%). Comorbidities were reported in 87% of patients with a mean Cumulative Illness Rating Scale-Geriatric (CIRS-G) sum score of 3.7 (SD: 2.7, range 0-10). All patients in the ITT cohort started trial treatment. Most patients were PET-2-negative (48/80, 60%) according to central review and therefore scheduled for a total of 4x BrECADD. Overall, 85% of patients received the scheduled number of cycles and 12% of patients received consolidating radiotherapy. Neutropenic fever occurred in 54% of patients and the TRMB rate was 77% (95%CI: 67-86). Sensory neuropathy of any grade occurred in 38% of patients, with grade >2 in one patient (1%). There were eight patients without centrally evaluated response assessment at EOT. Of the 76 patients with central response evaluation at EOT, 66/76 (87%), 9/76 (12%) and 1/76 (1%) had CR, partial remission or progressive disease, respectively. After a median follow-up of 23 months, PFS estimates at 1 year (1y) and 2 years (2y) were 95.1% (95%CI: 90-100) and 91.5% (95%CI: 85-98), respectively. Corresponding 1y-OS and 2y-OS rates were 96.2 (95%CI: 92-100) and 90.7% (95%CI: 83-98). No death was attributed to study treatment. Eleven second primary malignancies were reported during follow-up, most of which were other lymphomas (n=6). Conclusions: PET-guided BrECADD is feasible and safe in older patients but requires more frequent dose adjustments than in younger patients. Importantly, BrECADD resulted in an exceptionally high 2-year PFS rate, which is in the range observed for younger patients in HD21. We thus recommend PET-guided BrECADD as treatment strategy for newly diagnosed AS-cHL patients 61-75 years of age.

Introduction: Clonal Hematopoiesis (CH) is an age-related phenomenon in which somatic mutations accumulate in hematopoietic stem cells (HSCs). Despite CH occurring in >30% of patients (pts) with diffuse large B-cell lymphoma (DLBCL), its impact remains controversial. CH may promote DLBCL in two ways: it can seed mutations in the B-cell progenitors of germinal center (GC) B-cells, contributing to malignant transformation. Alternatively, the clonal and pro-inflammatory tumor microenvironment derived from CH may be relevant in lymphoma promotion. In the current study, we aim to: i) determine the prevalence of CH in a cohort of newly diagnosed DLBCL pts; ii) evaluate the clinical impact of CH on the risk of hematological toxicity of R-CHOP and on progression-free survival (PFS); iii) establish the correlation between CH and DLBCL genetic lesions; iv) evaluate at a single-cell level the frequency of co-occurrence of DLBCL driver mutations and CH mutations; v) evaluate if CH is enriched in cells of the lymphoma microenvironment compared to blood. Methods: Pts with DLBCL, who participated in either the IOSI-EMA003 study or the SAKK 38/19 trial (NCT04604067) underwent Cancer Personalized Profiling by Deep Sequencing (CAPP-seq). For the detection of DLBCL mutations, somatic copy number abnormalities, and BCL6 translocations, a validated customized lymphoid panel (LyV4.0) was used and applied to plasma cell-free DNA (cfDNA) and paired granulocytes DNA (to filter out polymorphisms). NMF clustering was used for DLBCL subtyping. To detect CH mutations, a validated customized myeloid panel (EOncoLAB v1.0) was used and applied to genomic DNA (gDNA) from granulocytes. Moreover, multiomic single-cell DNA sequencing and protein expression were explored in six pts with paired peripheral blood or bone marrow (BM) and disaggregated lymph nodes (LN). A customized Tapestri (MissionBio) panel was designed to target CH mutations of interest and to barcode the dominant DLBCL clone by covering trunk oncogene mutations, enabling simultaneous genotyping and phenotyping of different cell types (B cells, various T cell subtypes, and myeloid cells). Results: A total of 307 newly diagnosed DLBCL pts were analyzed by CAPP-seq. Clinical data are already available for 174 pts from the IOSI-EMA003 study. Overall, 44.3% of pts exhibited CH with a VAF >1%, surpassing the prevalence in the general population but aligning with findings in solid cancer series. DNMT3A was the most affected gene (22%), followed by TET2 (13%), with all other genes mutated in 3% or fewer pts. CH was associated with older age (p=0.006) and male sex (p=0.035). Univariate and multivariate analyses, adjusted for the IPI, showed no association between CH (HR=1.23, p=0.42), DNMT3A (HR=1.24, p=0.42), or TET2 (HR=0.56, p=0.12) mutations and PFS. Five-year PFS was 61.7% for wild-type (wt) CH and 50.6% for mutated CH (p=0.1), 59.6% for wt DNMT3A and 44.9% for mutated DNMT3A (p=0.07), and 54.7% for wt TET2 and 66.4% for mutated TET2 (p=0.28). Among CH mutations, TET2 mutations were significantly enriched in EZH2-mutated DLBCLs (p=0.01). Tapestri multiomic sequencing was performed on paired BM and LN from two DLBCL pts. One case (pt_1) harbored mutations in TET2 and CD79b/EZH2, while the other (pt_2), used as a control, had an ETV6 mutation but no CH mutations. CD79b/EZH2-mutated cells in pt_1 clustered entirely within the CD19+/CD10+ lymphoma population according to protein phenotyping, while TET2-mutated cells were ubiquitous across various cell compartments. These findings were consistent in both BM and LN samples. Moreover, CD79b/EZH2 mutations were mutually exclusive with respect to TET2 mutations, indicating that they were not seeded in the B cell that subsequently transformed to DLBCL. When considering solely cells of the microenvironment, TET2-mutated clones were enriched in the LN (6.4%) compared to the BM (2.6%) (p<0.001). Tapestri multiomic analyses on four additional pts are ongoing and will be presented during the congress. Conclusion: CH mutations, particularly DNMT3A and TET2 mutations, do not impact the outcome of pts with DLBCL. TET2 mutations are specifically associated with EZH2-mutated DLBCLs. Preliminary single-cell results demonstrate the enrichment of TET2-mutated cells in the nodal microenvironment of EZB DLBCL.

The Swiss Blood Stem Cell Transplantation and Cellular Therapy Group (SBST) leads a mandatory national registry for all hematopoietic stem cell transplants (HCT) and cellular therapies. After 25 years, information was available for 11,226 patients receiving an HCT (4031 allogeneic and 7195 autologous), including 925 pediatric patients. We compared patient characteristics and outcome by quinquennia 1997-2001, 2002-2006, 2007-2011, 2012-2016, and 2017-2021. There were numerous changes over time. Allogeneic transplant recipients became older (median age 33.7 vs. 54.3) and had more frequently unrelated donors and reduced intensity conditioning in later quinquennia. Similarly, age increased for recipients of autologous HCT (median 48.3 vs. 59.9). We did not see a significant drop in transplant activity during the SARS-CoV-2 pandemic. Analysis of outcome showed overall survival (relative risk (RR) of death 0.664 (0.529-0.832) and progression free survival (RR 0.708 (0.577-0.870) being improved over time comparing the latest to the first quinquennium adjusting for risk factors. Non-relapse mortality decreased in recipients of allogeneic HCT (RR: 0.371 (0.270-0.509)) over time but relapse risks did not. Outcome of autologous HCT improved as well across quinquennia, this improvement was mainly due to decreased relapse risks (RR 0.681 (0.597-0.777)), possibly related to maintenance treatment or rescue treatment for relapse mainly in myeloma patients. Cellular therapies other than allogeneic or autologous HCT, particularly chimeric antigen receptor T-cells (CAR-T) treatment have started to increase after 2019, year of approval of the first commercial CAR-T product in Switzerland. Data on chimeric antigen receptor T-cell treatment are too early for comparative analyses. Detailed analyses of changes over time are presented. This study includes all HCTs, and cellular therapies, data useful for quality assurance programs, health care cost estimation and benchmarking. Between 50% and 60% of patients are long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of haematological cancers with generally poor clinical outcomes. However, a subset of patients experience durable disease control, and little is known regarding long-term outcomes. The International T-cell Lymphoma Project (ITCLP) is the largest prospectively collected cohort of patients with PTCLs, providing insight into clinical outcomes at academic medical centres globally. We performed a long-term outcome analysis on patients from the ITCLP with available 10-year follow-up data (n = 735). The overall response rate to first-line therapy was 68%, while 5- and 10-year overall survival estimates were 49% and 40% respectively. Most deaths occurred prior to 5 years, and for patients alive at 5 years, the chance of surviving to 10 years was 84%. However, lymphoma remained the leading cause of death in the 5- to 10-year period (67%). Low-risk International Prognostic Index and Prognostic Index for T-cell lymphoma scores both identified patients with improved survival, while in multivariate analysis, age >60 years and Eastern Cooperative Oncology Group performance status 2-4 were associated with inferior outcomes. The favourable survival seen in patients achieving durable initial disease control emphasizes the unmet need for optimal front-line therapeutic approaches in PTCLs.

AIMS OF THE STUDY: Systemic amyloidoses are rare protein-folding diseases with heterogeneous, often nonspecific clinical presentations. To better understand systemic amyloidoses and to apply state-of-the-art diagnostic pathways and treatment, the interdisciplinary Amyloidosis Network was founded in 2013 at University Hospital Zurich. In this respect, a registry was implemented to study the characteristics and life expectancy of patients with amyloidosis within the area covered by the network. Patient data were collected retrospectively for the period 2005–2014 and prospectively from 2015 onwards. METHODS: Patients aged 18 years or older diagnosed with any subtype of systemic amyloidosis were eligible for inclusion if they were treated in one of the four referring centres (Zurich, Chur, St Gallen, Bellinzona). Baseline data were captured at the time of diagnosis. Follow-up data were assessed half-yearly for the first two years, then annually. RESULTS: Between January 2005 and March 2020, 247 patients were screened, and 155 patients with confirmed systemic amyloidosis were included in the present analysis. The most common amyloidosis type was light-chain (49.7%, n = 77), followed by transthyretin amyloidosis (40%, n = 62) and amyloid A amyloidosis (5.2%, n = 8). Most patients (61.9%, n = 96) presented with multiorgan involvement. Nevertheless, single organ involvement was seen in all types of amyloidosis, most commonly in amyloid A amyloidosis (75%, n = 6). The median observation time of the surviving patients was calculated by the reverse Kaplan-Meier method and was 3.29 years (95% confidence interval [CI] 2.33–4.87); it was 4.87 years (95% CI 3.14–7.22) in light-chain amyloidosis patients and 1.85 years (95% CI 1.48–3.66) in transthyretin amyloidosis patients, respectively. The 1-, 3- and 5-year survival rates were 87.0% (95% CI 79.4–95.3%), 68.5% (95% CI 57.4–81.7%) and 66.0% (95% CI 54.6–79.9%) respectively for light-chain amyloidosis patients and 91.2% (95% CI 83.2–99.8%), 77.0% (95% CI 63.4–93.7%) and 50.6% (95% CI 31.8–80.3%) respectively for transthyretin amyloidosis patients. There was no significant difference between the two groups (p = 0.81). CONCLUSION: During registry set-up, a more comprehensive work-up of our patients suffering mainly from light-chain amyloidosis and transthyretin amyloidosis was implemented. Survival rates were remarkably high and similar between light-chain amyloidosis and transthyretin amyloidosis, a finding which was noted in similar historic registries of international centres. However, further studies are needed to depict morbidity and mortality as the amyloidosis landscape is changing rapidly.

Background: Peripheral T-cell lymphomas (PTCLs), rare heterogeneous aggressive non-Hodgkin lymphoma (NHL) subtypes, generally have poor outcomes for all patient age groups. Few data are available on the clinical features and treatment outcomes for older adults with PTCLs. Given this gap in the literature, the purpose of this sub-analysis was to assess the clinical information, therapeutic approaches, and outcome of patients (>65 years old) included in the T-Cell Project 1.0 (clinicaltrials.gov: 01142674) and to investigate potential prognostic factors. Methods: The TCP 1.0 is a prospective international registry that collected clinical data and biological information of 1553 cases with PTCL at 75 institutions worldwide between 2006-2018. We identified 566 patients aged 65+. Baseline patient characteristics have been summarized with descriptive statistics. Survival analyses were performed using Kaplan-Meier method. Results: The median age of patients >65 years old was 72 years (range 65-90) with a slight male predominance (56.4%). The majority had ECOG 0-1 (65.8 %) and advanced stage III/IV (62%), and 44.5% of cases had extranodal involvement. The most frequent histological subtypes were PTCL NOS (236 cases, 41.7%), AITL (159, 28.1%), and ALCL ALK neg (69, 12.2%). The median follow-up for living patients was 36 months (2-139 months). Five year overall survival (OS) and progression-free survival (PFS) were 31% and 14%, respectively. B symptoms (p<0.001), weight loss (p<0.001), ECOG >1 (p<0.001), LDH>UNL (p<0.001), IPI 3-5 (p<0.001), beta2 microglobulin (p=0.002), suboptimal/reduced therapy (p<0.001), and age 75+ (p < 0.001) were correlated with lower OS in univariate analysis. Adverse prognostic features for PFS were B symptoms (p<0.001), weight loss >10% (p<0.001), ECOG >1 (p<0.001), advanced stage (p =0.04), LDH>UNL (p<0.001), IPI 3-5 (p=0.002), PIT 3-4 (p<0.001), suboptimal/reduced therapy (p<0.001), and age 75 + (p < 0.001). Interestingly, there were no differences in clinical characteristics between patients 65-74 years old and those 75+. However, optimal therapy was delivered to 89% of patients 65-74 and only to 67% in those aged 75 or more. Conclusion: In this prospective cohort of patients, we found no differences in clinical presentation between 65-74 and 75+ age groups. It seems they may have biologically similar disease. Older patients with PTCL are frequently treated with suboptimal/reduced therapy and exhibit a poorer outcome compared to those treated with optimal therapy. Based on the obtained results, the inclusion of otherwise fit older patients in ongoing clinical trials of front-line therapies incorporating targeted agents with a better tolerance is warranted.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive but potentially curable lymphoma. Rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone (R-CHOP) is the standard first-line regimen with cure rates nearing 60%. Over the last years many efforts have been made aiming at improving outcomes of first line therapy but none has resulted in improved overall survival over R-CHOP. Recently, genetic subtypes of DLBCL that go beyond the cell-of-origin and have distinct biology, clinical characteristics and different likelihood of response to specific therapies have been identified. One of these entities is represented by the MCD subtype harboring either the MYD88 L265P mutation, the CD79A/B mutation, or both. MCD has a dismal outcome when treated with R-CHOP but is sensitive to BTK inhibition. In addition to the genetic definition of specific subtypes, the possibility to use circulating tumour DNA (ctDNA) response assessment together with PET-response may establishe a new strategy for treatment decisions in patients with DLBCL. Methods: SAKK 38/19 (NCT04604067) is an ongoing exploratory multicohort phase II trial in patients (pts) with previously untreated DLBCL not otherwise specified (NOS). Adult pts with CD20-positive DLBCL NOS, ECOG performance status 0–2, candidates for 6 cycles of R-CHOP are eligible. At baseline, a liquid biopsy is perfomed and pts with MCD subtype are treated with the combination of R-CHOP plus acalabrutinib for 6 cycles (cohort A). Non-MCD pts receive 2 cycles of R-CHOP and based on the combined PET and ctDNA response assessment after cycle 2 they are allocated to one of three different cohorts: R-CHOP for 4 additional cycles in combination with acalabrutinib followed by 2 months of acalabrutinib single-agent (cohort B); 2 additional cycles of R-CHOP and 2 administrations of single-agent rituximab (cohort C); 4 additional cycles of R-CHOP (cohort D). Co-primary endpoints of the trial are: Progression free survival (PFS) (in Cohorts A, C and D) and complete remission (CR) rate (in Cohort B) Secondary endpoints: Adverse events in the cohorts treated with acalabrutinib-R-CHOP; overall survival; PFS in cohort B; CR rate in cohorts A, C and D; overall response rate; duration of response. The research was funded by: -Astra Zeneca -Hubacher Fund Keywords: aggressive B-cell non-Hodgkin lymphoma, liquid biopsy, ongoing trials Conflicts of interests pertinent to the abstract A. Stathis Honoraria: Eli Lilly, Bayer, Roche, Novartis, Janssen Oncology, AstraZeneca Research funding: ADC Therapeutics, Pfizer, Roche, Novartis, Bayer, Eli Lilly, MEI Pharma, Cellestia, Debiopharm Group, Merck/MSD, Abbvie, Amgen, AstraZeneca, Incyte, Loxo, and Philogen F. Hitz Consultant or advisory role Abbvie, Takeda and Roche G. Gritti Consultant or advisory role Roche, Takeda, Kite-Gilead, Ideogen, Genmab Educational grants: Janssen, Beigene, Sandoz Other remuneration: Clinigen, Ideogen, Beigene, Incyte, Novartis T. Zenz Honoraria: Roche, Abbvie, AZD, Beigene, Janssen, Gilead, Novartis

Introduction: Peripheral T-cell lymphomas (PTCLs) are a rare, heterogeneous group of hematological malignancies with extremely poor prognosis for almost all subtypes. Functional imaging based on 18-fluorodesoxyglucose positron emission tomography (PET), used for all other lymphoma subtypes, is challenging in PTCLs. Recently, also radiomics, i.e., the extraction of features from the images describing several underlying characteristics of the tumor such as heterogeneity, has demonstrated to provide a better characterization of the disease and reserve some prognostic value, but in this case, no experience in PTCLs lymphoma is available. It has been reported the prognostic value of TMTV in predicting the disease prognosis PTCLs through pre-treatment PET/CT imaging. However, these are limited data on pretreatment evaluation. Patients and methods: This study aimed to investigate whether the metabolic parameters on baseline PET could be used to predict the outcome of PTCL patients, and was conducted as a retrospective analysis of the prospective T-Cell Project 2.0 (NCT03964480). Patients were eligible if a baseline PET was available for central review. Anonymized PET images acquired within TCP 2.0 underwent a central review on WIDEN platform by a pool of nuclear medicine physicians. Tumor segmentation was performed with a percentage threshold of 41% of SUVmax in a lesion. TMTV was defined as sum of MTV through all the lesion of the body. Results: Sixty-six PTCLs patients were enrolled in this study from 8 international centers, and 48 were confirmed eligible and were evaluated in the present study. Median follow-up time was 18 months. PFS and OS at 2 years were 43% and 58% respectively. Median TMTV was 93 ml (25%–75% 30–419). A TMTV of 200 ml was chosen as threshold between high and low risk group for PFS. The same threshold was applied to OS. Overall, 27 patients (56%) were identified as having high TMTV without meaningful differences among PTCL subtypes. Patients with TMTV >200 ml had shorter 2y-PFS and -OS rates (27% and 35%, respectively), compared to patient with lower TMTV (62%, and 82%, respectively) describing both as statistically significant behavior (log-rank of 0.019 for PFS and 0.01 for OS). In univariate analysis, in addition to TMTV >200 ml, B-symptoms, PS >1, stage III/IV, ALC < 1 × 109/L, were adverse prognostic features for PFS, while LDH > UNL, PS > 1, Hb < 12 g/dL, albumin < 3.5 g/dL, and ALC < 1 × 109/L were correlated with lower OS rates. The research was funded by: Associazione Angela Serra Per La Ricerca Sul Cancro Keywords: Aggressive T-cell non-Hodgkin lymphoma, Diagnostic and Prognostic Biomarkers, PET-CT No conflicts of interests pertinent to the abstract.

The management of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in older patients is challenging due to increased morbidity, toxicity and reduced effectiveness of therapy in this vulnerable and difficult-to-treat population. Chimeric antigen receptor (CAR) T-cell therapies have become a breakthrough in the treatment of lymphoid malignancies, including DLBCL. Although CAR T-cell immunotherapy may significantly improve clinical outcomes, its toxicity raised concerns as to whether this therapeutic approach is beneficial for geriatric patients. The current paper summarizes the data from recent studies that evaluated the efficacy and safety of CAR T-cell products in older patients with DLBCL.

Introduction: In the treatment of advanced Hodgkin lymphoma (aHL), based on guidelines a multitude of treatment options are available. The availability of PET-guided decision-making and new therapeutic agents increase the complexity of the decision-making process. Methods: Thirteen experts of Swiss university and cantonal hospitals in Switzerland were asked to describe their institutional decision-making practice in aHL. Variables influencing the decision-making process were identified, standardized, and converted into decision trees for analysis of consent and discrepancies. The algorithms of all participating experts were analyzed with the objective consensus methodology. Results: Four decision criteria (age, fertility preservation, fitness, and interim PET) and 12 unique treatment regimens were identified. Consensus for the treatment of aHL for young and fit, as well as for older patients without comorbidity, was found. Large heterogeneity was identified with use of a variety of different regimens for unfit patients with aHL and for young female patients with a desire of fertility preservation. Conclusions: Four major decision criteria were identified allowing the representation of expert’s approach to first-line treatment of aHL. Among Swiss experts, consensus for a PET-guided curative treatment of aHL was identified. The use of a multitude of treatment regimens was observed for older and comorbid (unfit) aHL patients, highlighting the need for clinical trials and recommendations for this group of patients.