Packard, D

ABSTRACT Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell disorder with inferior outcomes compared with multiple myeloma (MM). However, studies describing outcomes after first progression and subsequent lines of therapy remain limited. We retrospectively analyzed 104 patients with pPCL who progressed after first‐line therapy treated at one comprehensive cancer center between 2006 and 2024. Clinical characteristics, treatments, time to next treatment (TTNT), and overall survival (OS) were assessed using Kaplan–Meier methods. All pPCL patients received novel agent–based induction. At the time of analysis, 63% had died; median OS was 39 months. High‐risk cytogenetics were present in 71%. The median TTNT after first‐line therapy was 10 months. Symptomatic progression occurred in 29% of patients and was associated with significantly inferior subsequent OS (13 vs. 34 months) compared with those experiencing asymptomatic biochemical progression. The TTNT progressively shortened with subsequent lines of therapy (3rd line: 6 months; 4th line: 4 months; 5th line: 3 months). Notable exceptions included pPCL patients with t (11;14) treated with anti‐BCL‐2‐based regimens, who achieved a median TTNT of 13 months. Additionally, 24 patients received anti‐BCMA CAR T‐cell therapy. With a median follow‐up of 21 months, their median TTNT was 32 months. pPCL is characterized by frequent disease progression and diminishing response duration with successive therapeutic lines. Symptomatic progression portends particularly poor outcomes. Anti‐BCL‐2‐based therapy in t (11;14) disease and anti‐BCMA CAR T‐cell therapy appear to provide more durable disease control and represent important advances for the management of progressed pPCL.

e19564 Background: Risk stratification in multiple myeloma (MM) relies on baseline staging systems and cytogenetic abnormalities, yet early relapse occurs in a subset of patients despite favorable risk features. Prior studies showed that clonal plasma cell S-phase assessed by flow cytometry using the plasma cell proliferation (PCPRO) assay at diagnosis and at autologous stem cell transplantation (ASCT) identifies biologically high-risk disease. The prognostic significance of clonal plasma cell S-phase following ASCT has not been well defined. Methods: We retrospectively analyzed MM patients who underwent ASCT within one year of diagnosis between January 1, 2013, and August 31, 2024. Patients without available post-ASCT clonal plasma cell S-phase assessment were excluded, yielding 150 evaluable patients. The proportion of clonal plasma cells in S-phase was determined by DNA content between G0/G1 and G2/M peaks and reported as a percentage. S-phase was assessed at the first post-ASCT marrow evaluation at day +60 (D45–75) and/or day +100 (D76–130), using the earlier assessment when both were available. Patients were classified as low (<2%) or high (≥2%) post-ASCT S-phase. Landmark progression-free survival (PFS) analyses were performed from the post-transplant assessment. Multivariable Cox models adjusted for cytogenetic risk, maintenance therapy, disease response at transplantation, International Staging System (ISS), and age. Results: Among 150 evaluable patients, 36 (24%) had high post-ASCT S-phase (≥2%) and 114 (76%) had low post-ASCT S-phase (<2%). Median age at ASCT was higher in the high S-phase group (64.5 vs 61.0 years; p=0.063), and advanced ISS stage (II/III) was more frequent (78% vs 57%; p=0.02). Cytogenetic risk, induction regimen, depth of response at transplantation, and maintenance therapy were similar between groups. Patients with high post-ASCT S-phase had significantly inferior PFS compared with those with low S-phase (median 17.0 vs 39.7 months; p=0.0003). On multivariable analysis, post-ASCT S-phase ≥2% remained independently associated with inferior PFS (HR 1.76, 95% CI 1.00–3.09; p=0.049). In an exploratory analysis among patients with paired S-phase assessments at the time of ASCT and post-ASCT, dynamic S-phase trajectories further stratified outcomes. Median PFS was longest in patients with persistently low S-phase (low→low; 39.7 months), intermediate in those converting from high to low S-phase (high→low; 27.2 months), and shortest in patients with newly emergent or persistently high post-ASCT S-phase (low→high: 15.0 months; high→high: 11.0 months) p=0.0019. Conclusions: Elevated proliferative activity of residual clonal plasma cells following ASCT identifies a biologically high-risk subset of MM patients with early relapse. Dynamic changes in post-ASCT S-phase further refine post-transplant risk stratification.

Abstract Introduction Solid tumors modify local angiogenesis and co-opt surrounding vasculature to maintain energy supply required for ongoing growth. This process is often complicated by metastasis and hemorrhage. Pulmonary tumors can rarely create intrapulmonary shunt physiology and hypoxemia in this manner; this has been described most often in bronchoalveolar carcinoma. We present a case of malignant intrapulmonary shunt occurring with spindle cell sarcoma, which resolved with arterial embolization. Case Presentation A 72-year-old male with a history of stage IV spindle cell sarcoma with abdominal, vertebral, and pulmonary metastases presented to an outpatient appointment with three weeks of fatigue and decreased exercise tolerance. He had no history of parenchymal lung disease nor any home oxygen requirement. In clinic, he was found to require 6L per minute of supplemental oxygen to maintain saturation of 88%. He was directly admitted to the oncology service. Initial laboratory evaluation was unremarkable. CT imaging demonstrated normal lung parenchyma, no pulmonary embolism, and an 11cm vascular tumor involving proximal branches of the local pulmonary artery (Figure). Transthoracic echocardiography (TTE) with agitated saline revealed a large intrapulmonary shunt. As the patient had limited response to oxygen therapy, this intra-tumoral shunt was deemed the most likely cause of his hypoxemia. Surgical resection was considered but was deemed to confer limited clinical benefit in the setting of multiple metastases. Embolization of the local pulmonary artery was therefore pursued with Interventional Radiology. The patient tolerated the procedure well with complete resolution of hypoxemia post-procedure. His energy and mobility improved, and he was discharged home. Three months later, he continued to require no supplemental oxygen. Discussion While shunt physiology is commonly part of the differential for hypoxemia, it is rarely described as an oncologic complication. This appears to be the first report of such pathology in a sarcoma patient, and the first to report shunt resolution through arterial embolization rather than surgical resection or systemic anti-tumor therapy. In addition, previous cases typically describe shunt detection via selective pulmonary arterial occlusion by Swan-Ganz catheter, whereas here the noninvasive TTE with agitated saline was sufficient. While the few existing reports highlight good response to lobectomy or pneumonectomy, this case highlights the potential for minimally invasive vascular intervention. Despite the metastatic nature of this patient’s disease, he received significant, rapid physiologic and functional benefit from a procedure with less morbidity. Maintaining suspicion of intra-tumoral shunt physiology is appropriate for patients with vascular pulmonary masses and hypoxemia. This abstract is funded by: None