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Background: The prognosis of multiple myeloma involving the central nervous system (CNS-MM) is poor. We report outcomes of CNS-MM treated with CNS-directed radiation therapy (RT)., Methods: We retrospectively reviewed patients with CNS-MM treated with CNS-directed RT from 2015 to 2024. CNS-MM was defined as having radiographic leptomeningeal or parenchymal disease, and/or pathologic CSF involvement. Complete response (CR) constituted having no atypical cells in CSF or resolution of radiographic disease. Otherwise, patients were categorized with partial response (PR) based on imaging, or stable disease (SD). The Kaplan-Meier method was used to estimate survival., Results: Of 45 patients with CNS-MM, 28 (62.2%) had high-risk disease. Median overall survival (OS) was 3.7 months (range: 0.4-52.2) postdiagnosis of CNS-MM. Most patients (n = 22, 48.9%) underwent craniospinal irradiation; 9 received whole brain RT (20%), and the others received focal brain or spine RT. The median dose was 20 Gy (2-30 Gy) in 10 fractions (1-15). Due to death or discharge to hospice before further follow-up of treatment efficacy (n = 24), only 21 patients (46.7%) were evaluable post-RT with adequate CSF or radiographic follow-up. For these evaluable patients, post-RT CR occurred in 14 patients (66.7%), PR in 5 (23.8%), and SD in 2 (9.5%). For patients with CR after RT, the median OS was 7.3 months (3-52.2) from CNS-MM diagnosis. Focal brain CNS-MM associated with improved OS and likelihood of attaining long-term survival with CNS CR., Conclusion: Aggressive multimodality therapy including RT may induce durable CNS control in a small subset of patients with CNS-MM, a high-risk population., Competing Interests: Disclosure All reported conflicts are outside the submitted work. GSM reports a patent for induced pluripotent stem cell-derived pancreatic beta cells, previous grants from ReproCell, Inc. and the AAI, and other work is supported by grants from the Radiological Society of North America / Canon Medical Systems (RSNA), an American Society for Radiation Oncology (ASTRO Residents/Fellows in Radiation Oncology Biology Seed Grant), and the American Society of Clinical Oncology (ASCO)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The combination of low-intensity chemotherapy and inotuzumab ozogamicin (INO), with sequential blinatumomab, is highly effective in older adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) and in relapsed or refractory B-cell ALL. Earlier, "dose-dense" administration of blinatumomab could lead to earlier and deeper measurable residual disease (MRD) responses and better outcomes., Patients and Methods: We performed a retrospective analysis of the safety and efficacy of a dose-dense regimen of mini-hyper-CVD (mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with mini-methotrexate and cytarabine), INO, and blinatumomab in patients with B-cell ALL., Results: Twenty-one patients were treated (frontline, n = 9; MRD consolidation, n = 4; relapsed/refractory, n = 8). In the frontline cohort, all patients achieved CR/CRi and MRD negativity by flow cytometry at the end of cycle 1. Across the frontline and MRD consolidation cohorts, 10/11 patients (91%) achieved next-generation sequencing MRD negativity at a sensitivity of 10 -6 , including 6/10 evaluable patients (60%) who achieved next-generation sequencing MRD negativity after cycle 1. The CR/CRi rate in the relapsed/refractory cohort was 63%, and all responders achieved MRD negativity by flow cytometry at the end of cycle 1. The 1-year overall survival rate for the combined cohort of the frontline and MRD-positive patients was 83%. No new safety signals were observed with the dose-dense mini-hyper-CVD, INO, and blinatumomab regimen., Conclusion: Dose-dense delivery of mini-hyper-CVD, INO, and blinatumomab was safe and resulted in rapid and deep MRD negativity in patients with B-cell ALL. This regimen is now being prospectively evaluated in both the frontline and relapsed/refractory settings., Competing Interests: Disclosure N.J.S, E.J., and H.K. have received research funding and honoraria from Amgen and Pfizer Inc. The rest of the authors have no relevant conflicts to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)