Introduction The checkpoint inhibitors (CI) nivolumab and pembrolizumab which target PD1 are established treatments for relapsed/refractory classic Hodgkin Lymphoma (cHL). The Keynote-087 and -204 trials included patients who were unsuitable for autologous stem cell transplant (ASCT). Published data suggests that patients who receive CI prior to ASCT have better outcomes (Spinner et al, Blood 2023 & Desai et al AJH 2022). The effect of CI prior to ASCT was investigated in a retrospective single centre analysis. Methods The local transplant database was used to identify adult and paediatric patients who had an ASCT for relapsed/refractory cHL 2017-2024. Demographic, treatment, stem cell collection and response data was collected. Analysis was performed using Graphpad Prism version 10. Results 94 patients were identified with median age 27 (IQR 20-39, range 12-72) and equal numbers of female and male patients. First line treatment was ABVD or AAVD (64) or OEPA (22) in most patients. 41 patients were primary refractory. Initial salvage was with GEMP/GDP in 58 patients. 44 received brentuximab vedotin (BV). 50 patients had ASCT consolidation after 1st line salvage and 44 had 2 or more lines of salvage prior to ASCT. Prior to ASCT 17 (18%) patients were not in CR. 16(17%) patients had received radiotherapy at some point in their treatment. The CI group included 23 patients at any line of salvage (nivolumab 4; pembrolizumab 19). CI was given as 1st/2nd/3rd line salvage in 5/11/7 patients respectively. 20 patients had a CI as their last line of therapy prior to ASCT. 4 patients had a CI in combination with BV. The median number of CI doses was 4.5 (IQR 3.25-7.75) with the last dose given a median of 42 days pre ASCT (IQR 31-76). All patients were conditioned with LEAM (lomustine, etoposide, cytarabine, melphalan). Post ASCT, 3 patients had consolidative radiotherapy and 6 received BV maintenance (4 in no-CI group, 2 in CI group). CI treatment pre-ASCT resulted in improved progression free survival (PFS) (p=0.047) with 0 relapses in the CI group at analysis and 2 year PFS of 79.1% (CI 69.1-90.6) in the no-CI group. In multivariate analysis female sex was associated with improved PFS (HR 0.28 [CI 0.086-0.79], p=0.021) and failure to be in CR pre ASCT was associated with reduced PFS (HR 4.3 [1.15-13.5] p=0.017). There was a trend towards worse outcomes in primary refractory patients (HR 2.64 [0.95-7.53] p=0.061). Age, prior BV treatment and number of lines of therapy pre ASCT were not associated with PFS. A HR was not calculable for CI therapy as there were 0 events. Overall survival was 87.7% (95% CI 75-100) at 5 yrs for the whole cohort with 5 deaths. The CI group had fewer patients in CR prior to ASCT (65% vs 87%, p=0.017) and fewer patients who had received only 1 line of salvage prior to ASCT (8.6% vs 68%, p<0.01). There was shorter median follow up in the CI group (18 vs 29 months). 15 patients relapsed post ASCT. 13 patients received CI for relapse and 9 had allogeneic stem cell transplants. Immune complications affected 5 patients (2 myocarditis, 1 colitis, diabetes and pneumonitis). 14 patients were on a CI at time of stem cell harvest with median time between last CI dose and collection of 27.5 days. The mean CD34+ stem cells harvested was lower in CI treated patients 3.41 vs 4.23 (106/kg, p=0.025). CI was given a median of 30 days pre-harvest (IQR 20.8-35.5). CD34 doses infused were not associated with PFS. Conclusions Previous CI treatment is associated with improved PFS post ASCT in our centre despite lower pre-ASCT CR rates and more lines of salvage therapy. Failure to be in CR pre ASCT was associated with shorter PFS but despite the CI group having fewer patients in CR, they had superior PFS. There is a trend toward reduced PFS in patients who were initially primary refractory. It is unclear if R/R patients treated with CI benefit from routine ASCT. Spinner et al, Blood 2023 found a PFS of 91% at 4 years in CI treated patients post ASCT. Our data supports this and suggests pre-ASCT response is less important in CI treated patients. Most of the no-CI group were salvaged with subsequent CI for relapse post ASCT with or without subsequent allogeneic transplant. CI treatment prior to ASCT may alter cHL disease biology leading to increased sensitization to subsequent high dose cytotoxic chemotherapy although more exploratory data assessing the mechanism is needed. We are planning a multi-centre analysis to investigate further.

BACKGROUND:Daratumumab, bortezomib, thalidomide, and dexamethasone (Dara-VTd) is the current standard of care in Europe based on the CASSIOPEIA study, which demonstrated improved depth of response and progression-free survival when daratumumab is added to VTd. PATIENTS AND METHODS:We conducted a retrospective analysis of patients treated with VTd or Dara-VTd at the Royal Marsden Hospital (RMH). Post-transplant response was assessed by biochemical response and minimal residual disease (MRD) using flow cytometry (sensitivity 10⁻⁵), with additional stratification by cytogenetic risk. RESULTS:A total of 173 patients (103 Dara-VTd, 70 VTd) with balanced baseline characteristics were included; 150 patients (87%) had a full cytogenetic panel. Median follow-up was 18.6 months. Post-transplant overall response rate was higher with Dara-VTd than VTd (97.1% vs. 87.1%), as was MRD negativity (78.6% vs. 55.7%). While Dara-VTd consistently outperformed VTd, the benefit decreased in patients with multiple high-risk cytogenetic abnormalities. Twenty-four-month progression-free survival was 97.3%, 94.1%, and 63.9% for patients with 0, 1, and ≥ 2 abnormalities treated with Dara-VTd, compared with 82.6%, 61.9%, and 55.6% for VTd, respectively. CONCLUSION:Adding daratumumab to VTd improves post-transplant response and MRD negativity in real-world practice. The magnitude of benefit diminishes with increasing numbers of high-risk cytogenetic abnormalities, supporting the value of risk-adapted strategies and real-world MRD assessment in treatment evaluation.

Systemic Mastocytosis (SM) is a multifaceted clinically heterogeneous disease. Advanced SM (AdvSM) comprises three entities: aggressive SM (ASM), mast cell leukaemia (MCL) and SM with an associated hematologic neoplasm (SM-AHN), the latter accounting for 60-70% of all AdvSM cases. Detection of a disease-triggering mutation in the KIT gene (esp. KIT D816V) in >90% of the patients with ASM or SM-AHN has led to a significant improvement in therapeutic options by the implementation of two KIT-targeting kinase inhibitors: midostaurin and avapritinib. Although complete remissions have been reported, neither of these targeted agents is 'curative' in all patients and the duration of responses varies. The median overall survival, depending on the WHO subtype and scoring result, is approximately 1 to 4 years. Although the European Competence Network on Mastocytosis (ECNM) and American Initiative in Mast Cell Diseases (AIM) consensus groups recommend allogeneic haematopoietic cell transplantation (allo-HCT) in drug-resistant and other high-risk patients, there is a relative lack of information to guide clinicians on which patients with AdvSM should be considered for transplant, and how KIT inhibitors may fit into the transplant algorithm, including their use pre- and post-transplant to optimise outcomes. Following the generation of an expert panel with a specialist interest in allo-HCT and mastocytosis, these best practice recommendations were generated according to the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonisation and guidelines and ECNM methodology. We aim to provide a practical, clinically relevant and up-to-date framework to guide allo-HCT in AdvsM in 2024 and beyond.

Advanced systemic mastocytosis (AdvSM) is a rare, life-limiting mast cell (MC) neoplasm, with approximately 70% patients having an associated haematological neoplasm (AHN). Avapritinib, a selective tyrosine kinase inhibitor targeting KIT D816V, has shown potent activity translating clinically into durable responses in the phase 1 EXPLORER (NCT02561988) and phase 2 PATHFINDER (NCT03580655) studies. We report three patients with AdvSM-AHN on avapritinib who achieved complete remission (CR) of SM and were successfully bridged to allogeneic haematopoietic cell transplant (allo-HCT). Two cases additionally highlight the risk of clonal evolution within the AHN component and requirement for close monitoring while on targeted therapy.

Refined prediction of early relapse following standard-of-care (SoC) autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) could inform real-world risk-stratified post-ASCT strategies. We investigated the impact of double hit genetics (≥2 adverse markers: t(4;14), t(14;16), t(14;20), gain(1q), del(17p)) on outcome in 139 NDMM patients who underwent SoC ASCT between January 2014 and October 2019 at our center. Double hit genetics were associated with a significantly shortened progression-free survival (hazard ratio [HR] = 4.27, P < 0.001) and overall survival (HR = 4.01, P = 0.03), and characterized most early relapses. Our results support the real-world utility of extended genetic profiling for improved risk prediction in NDMM.

Allogeneic hematopoietic cell transplantation (allo-HCT) with reduced intensity conditioning (RIC) is an option for elderly patients with acute lymphoblastic leukemia (ALL). We retrospectively compared results of RIC-allo-HCT from either a matched sibling donor (MSD, n = 209) or matched unrelated donor (MUD, n = 209) with autologous (auto, n = 142) HCT for patients aged 55 years or more treated in first complete remission (CR1) between 2000 and 2018. The probabilities of leukemia-free survival (LFS) at 5 years were 34% for RIC-allo-HCT versus 39% for auto-HCT (p = 0.11) while overall survival (OS) rates were 42% versus 45% (p = 0.23), respectively. The incidence of relapse (RI) and non-relapse mortality (NRM) was 41% versus 51% (p = 0.22) and 25% versus 10% (p = 0.001), respectively. In a multivariate model, using auto-HCT as reference, the risk of NRM was increased for MSD-HCT (Hazard ratio [HR] = 2.1, p = 0.02) and MUD-HCT (HR = 3.08, p < 0.001), which for MUD-HCT translated into a decreased chance of LFS (HR = 1.55, p = 0.01) and OS (HR = 1.62, p = 0.008). No significant associations were found with respect to the risk of relapse. We conclude that for patients with ALL in CR1, aged above 55 years, auto-HCT may be considered a transplant option alternative to RIC-allo-HCT, although its value requires verification in prospective trials.

Background Haemato-oncology patients are likely to be referred later to palliative care than patients with solid tumours, despite experiencing similar symptom burden. Patients prior to stem cell transplant may benefit from symptom control, advance care planning and shared decision-making, and previous studies have demonstrated feasibility and benefit of such a service. However, the views of patients are not yet established, and are vital to ensure acceptability of the service. Aims To identify areas where a palliative care team may help to support patients being considered for a stem cell transplant, and to explore the attitudes and perceptions of patients towards palliative care at this time. Design A qualitative study including interviews ( N = 12) and a focus group ( N = 4) for patients pre- and post-transplant, using a semi-structured format via telephone, online video-conferencing and face-to-face discussions. Recordings were transcribed and analysed using thematic analysis. Setting A tertiary cancer centre in the UK. Findings Themes identified were the following: Identified needs, Information and decision-making, Importance of relationships, Changing perceptions of what palliative care means, and The future. Patients associate palliative care with terminal care due to indirect experiences. Patients were open to palliative care once its purpose was explained and described emotional and physical needs relevant to early palliative care. Conclusions The involvement of early palliative care alongside haematology treatment prior to stem cell transplant may improve quality of life for patients and facilitate shared decision-making at a crucial stage of treatment. Early palliative care should be offered alongside haematology care around the time of stem cell transplant, with information provided to patients regarding its role.

Enteropathy-associated T-cell lymphoma (EATL) is a rare but serious complication of celiac disease. Diagnosis is challenging. Patients can present with weight loss, abdominal pain, and diarrhea or acutely with bowel perforation or obstruction. Patients often present with advanced disease. Malnutrition further limits treatment options. Early diagnosis is important to start aggressive treatment strategies. However, even with prompt diagnosis, prognosis remains poor with a high mortality rate. We report the first documented case of sole tonsillar involvement, a rare extraintestinal and extranodal site of disease, leading to EATL diagnosis. We also highlight some of the challenges in diagnosing EATL.

PCNSL response assessments rely upon contrast enhanced magnetic resonance imaging (MRI) for the evaluation of response. EOT MRI is not fully accurate in anticipating cure or relapse as patients (pts) in complete response (CR) will recur while some patients in partial response (PR) will not. We aimed to determine the prognostic value of EOT 18F-choline PET as novel adjunctive study at the RMH for pts with PR and CR at EOT MRI following first line (1L) treatment. Clinical data was collected from pts treated at RMH for PCNSL between August 2009 and March 2020. Kaplan Meier survival analysis for progression free survival (PFS) and overall survival (OS) was performed for pts who were in PR (residual contrast visible) or CR (no residual contrast) on their EOT MRI. PFS and OS was also calculated for pts with residual choline (PET-PR) vs no residual choline uptake (PET-CR) on PET. PFS is calculated from time from 1st treatment to progression/death. OS is calculated from time from 1st treatment to death of any cause. 70 pts were treated for PCNSL. 40/70 pts completed all intended induction treatment. The majority that did not complete treatment was due to progression/death. 7 pts that completed intended treatment were excluded from evaluation as 3 had progressive disease (PD) on their EOT MRI and EOT MRI was not available for 4. All 3 patients with PD had choline uptake on their EOT scan. For the remaining 33 evaluable pts the table below summarises their outcomes. After this EOT timepoint, 17 of these 33 patients proceeded to consolidation with either whole brain radiotherapy or autologous stem cell transplant following 1L chemotherapy.Table: 633P(n)= Number of pts. (*)=Omitting pts where no PET performed. (+)= Unable to calculate upper bound due to insufficient number of eventsResponse categorynMedian PFS (years) (95% CI)p-valueMedian OS (years) (95% CI)p-valuen receiving consolidation after 1L therapyAll pts332.2 (1.2, 7.0)5.0 (2.0, +)17EOT MRI outcomeCR171.6 (0.6, 5.7)0.085.0 (1.2, +)0.406PR165.2 (1.6, +)6.0 (1.8, +)11EOT PET outcome*CR191.9 (0.8, 7.0)0.985.0 (1.8, +)0.737PR52.2 (0.8, +)4.8 (1.5, +)3 Open table in a new tab Patients achieving PR on MR or PET had similar OS to those with CR. This could be attributed to higher proportion of pts with PR receiving consolidation therapy.