Medulloblastoma in an Adult With Late Extraneural Metastases to the Mediastinum

Background . Medulloblastoma, although the most common brain tumor of childhood, is exceedingly rare in adults. These tumors have a propensity for local recurrence and to metastasize along the leptomeninges; however, extraneural metastases are very rare and typically occur in the bone or bone marrow. We have not come across any case in literature of medulloblastoma with mediastinal metastases in an adult. Case Presentation . We report a case of medulloblastoma in a 38-year-old lady who was treated with surgery followed by craniospinal radiation. Ten years later she presented with hoarseness from true vocal cord paralysis. She was diagnosed to have infiltrating metastases of her medulloblastoma to the mediastinum, which was confirmed by biopsy. There was no local recurrence. This was treated with chemotherapy followed by stem cell rescue, and she remained progression free for 2 years. Conclusion . Medulloblastomas are rare in adults and can present with late extraneural metastases following treatment. Although most common reported sites are bone and bone marrow, late metastases to other unexpected areas like the mediastinum are possible too and warrant awareness. This can be treated with chemotherapy followed by high-dose chemotherapy and stem cell rescue in a young patient with good performance status

A phase II study of addition of pracinostat to a hypomethylating agent in patients with myelodysplastic syndromes who have not responded to previous hypomethylating agent therapy

Hypomethylating agents (HMAs) are standard of care for higher-risk myelodysplastic syndromes (MDS). However, less than half of patients achieve objective responses and most eventually lose their response. Pracinostat is a pan-histone deacetylase inhibitor with demonstrated activity in advanced myeloid malignancies. This phase II study explored the benefit of adding pracinostat to HMAs in MDS patients who did not respond to single-agent HMA treatment. The goal was to estimate the clinical improvement rate [complete remission (CR), marrow CR, partial response (PR) and haematological improvement]. Group 1 included patients with primary/secondary HMA failures; Group 2 included those who did not achieve response but had stable disease (SD) after single-agent HMAs. Forty-five patients (39 Group 1, 6 Group 2) received a median of 3 cycles. Among all patients, 1 (2%) had CR, 7 (16%) had marrow CR and 18 (40%) had SD; disease progression occurred in 3 (7%). Median overall survival was 5 center dot 7/5 center dot 6 months for Group 1/2. Grade >= 3 adverse events occurred in 38 patients (84%) leading to treatment discontinuation in 12 (33%). Adding pracinostat to HMAs did not improve outcomes in patients previously treated with HMAs. Frequent dose modifications/early discontinuation resulted in suboptimal drug exposure. A reduced pracinostat dose may improve tolerability and efficacy

Safety and efficacy of polatuzumab vedotin + obinutuzumab for relapsed/refractory non‐Hodgkin lymphomas: A phase IB/II study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171136/1/ajh26400-sup-0004-FigureS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171136/2/ajh26400-sup-0005-FigureS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171136/3/ajh26400-sup-0003-FigureS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171136/4/ajh26400_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171136/5/ajh26400-sup-0002-FigureS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171136/6/ajh26400.pd

A Randomized, Placebo-Controlled, Phase II Study of Pracinostat in Combination with Azacitidine (AZA) in Patients with Previously Untreated Myelodysplastic Syndrome (MDS)

Background: Pracinostat (PR) is a potent oral inhibitor of histone deacetylases (HDAC's), selective for class I, II and IV isoforms. A pilot phase Ib study of pracinostat in combination with AZA in higher risk MDS demonstrated a complete response (CR)/CR with incomplete blood count recovery (CRi) rate of 89% (Proc ASH:3821, 2012). The current study was designed to rigorously assess the clinical activity of this combination in a multi-center environment, including a placebo-controlled comparator group. Methods: Eligibility includes age ≥18 years, previously untreated intermediate risk-2 or high-risk MDS by IPSS, >5% and <30% marrow blasts, PS≤2, and adequate organ function. Treatment is AZA, 75 mg/m2 days 1-7 or days 1-5/days 8-9 plus PR or placebo (PL), 60 mg 3 days/week for 3 weeks. Cycles are repeated every 28 days until disease progression lack of benefit, or intolerance. Randomization was stratified by IPSS risk group with a planned sample size of 100. The primary endpoint is confirmed CR within 6 cycles, based on IWG criteria (Cheson, 2006). CR rates are calculated for each group with 95% CI's and compared using Chi-square testing. Time-to-event secondary endpoints (PFS, EFS, OS) are analyzed by Kaplan-Meier and hazard ratios calculated. The primary analysis population is defined as all randomized and treated patients. Results: Between June 2013 and August 2014, 102 patients were randomized and treated at 24 U.S sites. Baseline characteristics: median age 69 (26-90), 69% M:31% F, PS 36% 0/58% 1/6% 2. IPSS Risk categories, 67% INT2/33% High risk. Treatment-related 12%, median blasts 13% (2.2 - 27). Efficacy (PR vs. PL): As of June 30, 2015, CR within 6 cycles was 18% vs. 31%; hematologic improvement was 35% vs. 55%; PFS was 10.7 vs. 9.2 mo. (HR=0.93, p=NS); EFS was 8.6 vs. 9.0 mo. (HR=0.82, p=NS); OS was 15.7 vs. 18.8 mo (HR=1.21, p=NS). Pracinostat resulted in a higher rate of discontinuations for adverse events (AE's), 26% vs. 10%, predominantly within the first 2 cycles of treatment. Notable grade ≥3 AE's: thrombocytopenia, 47% vs. 26%; febrile neutropenia 33% vs. 18%; fatigue, 24% vs. 0%. Exploratory sensitivity analyses, censoring patients not starting cycle 5 (n=54), showed the following HR's all favoring Pracinostat: PFS=0.37, EFS=0.33, OS=0.59. Conclusions: Pracinostat failed to improve the clinical effectiveness of AZA in this population of higher risk MDS. This appears related to a higher rate of early study discontinuation in the PR group, primarily due to AE's. Exploratory analyses suggest that patients able to tolerate PR for at least 4 cycles may derive benefit. Disclosures Berdeja: Novartis: Research Funding; BMS: Research Funding; MEI: Research Funding; Janssen: Research Funding; Onyx: Research Funding; Abbvie: Research Funding; Curis: Research Funding; Array: Research Funding; Celgene: Research Funding; Acetylon: Research Funding; Takeda: Research Funding. Komrokji:Celgene: Consultancy, Research Funding; Incite: Consultancy; Novartis: Speakers Bureau; GSK: Research Funding. Lyons:US Oncology: Research Funding; Amgen: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Sekeres:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; TetraLogic: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees