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Based on phase 3 trials, maintenance therapy after autologous stem cell transplantation (ASCT) has become the standard of care in multiple myeloma (MM). We examined the trends in maintenance therapy in a large group of patients (2530) transplanted at a single institution over two decades. Majority (n = 1958; 77%) had an ASCT within 12 months of diagnosis (early ASCT). Maintenance was employed in 39% of the patients; 42% among early ASCT and 30.5% among delayed ASCT. Most common maintenance approach was an IMiD (61%), followed by a PI (31%), or a PI + IMiD (4%). Patients with high-risk FISH received PI-based maintenance more frequently. The PFS was superior with maintenance (36 vs. 22 months, p < 0.001); 37 vs. 25 months for early ASCT (p < 0.001) and 29 vs. 17 months for delayed ASCT (p = 0.0008). OS from ASCT was higher with maintenance for the whole cohort at 93 vs. 73 months (p < 0.001). OS from diagnosis was also better for the whole cohort with maintenance therapy, 112 vs. 93 months (p < 0.001). The improvement in PFS and OS was seen in high-risk and standard risk disease. The experience with maintenance therapy post ASCT for myeloma in a non-clinical trial setting confirms the findings from the phase 3 trials.

Abstract Aleukemic leukemia cutis (LC) is an extremely rare clinical presentation. All patients eventually develop acute leukemia, mostly monocytic and myelomonocytic types. It is a diagnostic challenge, resolved by careful immunophenotyping and cytochemistry. The diagnosis indicates a poor prognosis. Here, we report a case of an 85-year-old white male with LC, who had normal peripheral blood and bone marrow histology. The fragility of our patient precluded any definite anti-leukemic therapy.

Spur cell haemolytic anaemia (SCA) is a form of anaemia that can be seen in patients with severely impaired liver function or advanced cirrhosis. It is associated with high mortality. The treatment options for SCA secondary to cirrhosis are limited. Our patient is a middle-aged man who developed SCA and was not a candidate for liver transplantation or splenectomy. High-dose steroids helped ameliorate haemolysis and improve anaemia and general condition of our patient.

Cholangiocarcinomas (CCA) are uncommon malignancies that present late and have a poor prognosis. The patients may remain undiagnosed for many years because of non-specific presentation. CCA metastasises commonly to liver and adjacent lymph nodes. It can rarely metastasise to bone, lung, colon, pancreas, adrenal glands and spleen. Multiple treatment options are available including surgery, chemotherapy, radiotherapy and photodynamic therapy. The tumours have high rate of recurrence and most patients require palliative care. Our patient is a middle-aged man who presented with pain in right ring finger, workup of which revealed digital metastasis from underlying cholangiocarcinoma.

Non-cirrhotic, non-malignant portal vein thrombosis (PVT) is commonly secondary to inherited or acquired prothrombotic states. However, even after extensive workup, 25% of patients with PVT have no apparent prothrombotic aetiology identified (idiopathic PVT). Inherited conditions include factor V Leiden, PT mutation and protein C/S/AT deficiency. Acquired conditions include APS, PNH and BCR-ABL 1-negative myeloproliferative neoplasms (MPN). BCR-ABL-1 negative MPNs are the most frequent underlying prothrombotic risk factor for PVT (15%–30%). However, peripheral blood counts often remain within normal ranges in these patients with MPN because of portal hypertension sequel. Despite suggestive features of MPN in bone marrow, these patients lack adequate diagnostic criteria and are classified as occult MPN. The discovery of recurrent molecular abnormalities such as CALR gene exon 9 mutation presented a crucial advance in the diagnosis of occult MPNs. In our patient, the diagnosis of MPN was made on this basis, despite lack of peripheral evidence of MPN.

Aggressive systemic mastocytosis (ASM) is characterized by mast cell accumulation in systemic organs. Though ASM may be associated with other hematological disorders, the association with pure red cell aplasia (PRCA) is rare and has not been reported. Pure red cell aplasia (PRCA) is a syndrome, characterized by normochromic normocytic anemia, reticulocytopenia, and severe erythroid hypoplasia. The myeloid and megakaryocytic cell lines usually remain normal. Here, we report an unusual case of ASM, presenting in association with PRCA and the management challenges.

BackgroundIn May 2024, the FDA approved tarlatamab, a Delta-like ligand (DLL3)/CD3-targeted bispecific T-cell engager, for patients with extensive-stage small cell lung cancer (SCLC) with disease progression following platinum-based chemotherapy and at least one other prior line of therapy. We aim to examine the cellular immune cell profile changes seen in patients receiving this therapy in standard-of-care (SOC) practice.MethodsPatients who received tarlatamab at Mayo Clinic Rochester consented to research blood. Immune phenotyping was performed on whole blood by flow cytometry and analyzed by Kaluza. Data analysis was performed with Excel and PRISM.ResultsThirteen patients with a median age 64 years (range 41-80) who were treated and evaluable for clinical response were included, 53% were women. All had a history of tobacco use.Nine (69%) patients had progressive disease (PD) after a median of 2 cycles, whereas 4 patients had partial response (PR) or stable disease (SD) after at least 2 cycles and remain on therapy (no-PD). Compared to the no-PD group, those whose disease PD early had higher levels of exhausted CD8 T cells at baseline (PD1+TIGIT+CD57+, PD vs no-PD, cells/µL: 17.4±5.6, 7.6±2.6, p=0.006). Interestingly, a CD8 TIGIT+PD1negCD57neg population was also identified which was higher at baseline (PD vs no-PD, cells/µL: 21.5±16.9, 12.2±5.33, p=0.039) and decreased significantly for the PD group from baseline to day 7 (21.5±16.9 to 9.30±10, p=0.039; figure 1A). This population was found to have a different functional profile than the exhausted phenotype in other solid tumors and its role in small cell lung cancer has not been defined. At day 7, compared to the no-PD group, the PD group also had a high level of B-cells (PD vs no-PD, cells/µL: 10.3±15, 4.07±1.83, p=0.027), classical monocytes (PD vs no-PD, cells/µL: 365±279, 226±121, p=0.035), and immunosuppressive monocytes (CD14+HLA-DRneg monocytes, cells/µL: 119±93, 33±42, p=0.05). In addition, the no-PD group had a statistically significant decrease from baseline to day 7 in intermediate monocytes (32.5±7.9 to 17±2.6, p=0.049; figure 1B).ConclusionsIn this study investigating the SOC outcomes of tarlatamab, early PD was associated with higher presence of exhausted CD8 T cells, B cells, and immunosuppressive monocytes. Analysis of additional patients will be shared at SITC meeting.Abstract 844 Figure 1ACD8 T cell phenotype associated with clinical response[Image Omitted. See PDF.]Abstract 844 Figure 1BMonocyte phenotype associated with clinical response[Image Omitted. See PDF.]

BackgroundDespite the success treating hematologic malignancies, chimeric antigen receptor T-cell (CAR T) therapies face challenges in solid tumors due to lack of targets that distinguish tumor from normal cells. Epithelial growth factor receptor (EGFR) plays a critical role in oncogenesis across several cancers and is often upregulated.1 While monoclonal antibodies targeting EGFR have demonstrated efficacy, these approaches are often limited by on-target, off-tumor toxicities, such as skin and gastrointestinal toxicity, which constrains dose escalation and efficacy.2 A2B395 is an allogeneic, logic-gated, EGFR-targeted, Tmod CAR T therapy designed to address these limitations and provide a convenient and consistent off-the-shelf option. This therapy incorporates 2 CARs: an activator targeting EGFR and a blocker targeting human leukocyte antigen (HLA)-A*02. The activator recognizes EGFR on both tumor and normal cells, whereas the blocker inhibits CAR T activity against normal cells with preserved HLA expression, decreasing the risk for graft-vs-host disease (ie, on-target, off-tumor toxicity).3 To address potential graft-vs-host response, a short-hairpin RNA expression module targeting beta-2 microglobulin is included in the Tmod construct, which significantly reduces major histocompatibility complex class I levels and subsequent host immune response.4 Importantly, the Tmod system is modular and adaptable to multiple targets. Initial data on autologous Tmod CAR T therapy suggest reduced off-tumor toxicity and encouraging clinical efficacy.5 A2B395 represents a novel approach for targeting EGFR-expressing solid tumors with HLA-A*02 loss of heterozygosity (figure 1).MethodsDENALI-1 is a phase 1/2, open-label, nonrandomized study evaluating the safety and efficacy of A2B395 in adults. Patients are enrolled through BASECAMP-1 (NCT04981119), a master prescreening study that identifies patients with HLA loss of heterozygosity at any time in the course of their disease via next-generation sequencing. Key inclusion criteria include histologically confirmed recurrent, unresectable, locally advanced, or metastatic cancers associated with EGFR expression, including colorectal, non-small cell lung, squamous cell head and neck, triple-negative breast, and renal cell cancers. Patients must have received ≥1 line of prior therapy, such as a checkpoint inhibitor, molecular targeted therapy, or chemotherapy. The primary objective of phase 1 is to evaluate safety, tolerability, and the recommended phase 2 dose using a Bayesian optimal interval design for dose escalation. The dose-expansion phase will confirm recommended phase 2 dose and collect biomarker data. Phase 2 will assess overall response rate per RECIST v1.1.ResultsThe first patient was enrolled on DENALI-1 in May 2025. Dose escalation is ongoing (figure 2).AcknowledgementsThe authors would like to thank the patients, their families, and their caregivers for participating in this trial; the screeners, clinical research coordinators, study nurses, data managers, and apheresis teams at each study site; and A2 Bio. Medical writing support was provided by Jennifer M. Kulak, PhD, of ApotheCom (Yardley, PA) and funded by A2 Bio.Trial RegistrationClinicalTrials.gov, NCT06682793ReferencesThe Cancer Genome Atlas (TCGA) Research Network. Accessed June 2021. https://www.cancer.gov/tcgaMacdonald JB, et al. Cutaneous adverse effects of targeted therapies: Part I: Inhibitors of the cellular membrane. J Am Acad Dermatol. 2015;72(2):203–218.Hamburger AE, et al. Engineered T cells directed at tumors with defined allelic loss. Mol Immunol. 2020;128:298–310.DiAndreth B, et al. The Tmod cellular logic gate as a solution for tumor-selective immunotherapy. Clin Immunol. 2022;241:109030.Grierson PM, et al. 588 EVEREST-1: initial safety data from a seamless phase 1/2 study of A2B530, a logic-gated Tmod CAR T-cell therapy, in patients with solid tumors associated with CEA expression also exhibiting HLA-LOH. J ImmunoTher Cancer. 2024;12(Suppl_2):A670-A671.Kirtane K, et al. Logic-gated, allogeneic Tmod chimeric antigen receptor T-cell (CAR T) therapy targeting epidermal growth factor receptor (EGFR) in advanced solid tumors with human leukocyte antigen (HLA) loss of heterozygosity (LOH): DENALI-1 trial. J Clin Oncol. 2025;43(16 suppl): TPS2677.Ethics ApprovalThis trial was approved by each site’s institutional review board.Abstract 585 Figure 1Logic-Gated CAR T With the Goal to Reduce Toxicity: MSLN (Activator) and HLA-A*02 (Blocker) [6][Image Omitted. See PDF.]Abstract 585 Figure 2DENALI 1 dose escalation study design[Image Omitted. See PDF.]