7 research outputs found
Therapeutic outcomes using subcutaneous low dose alemtuzumab for acquired bone marrow failure conditions
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Abstract 1170: Socioeconomic disparities in patients with esophageal cancer at time of diagnosis: A national cancer data base analysis
No full textA practical guide to the management of dysphagia in patients with metastatic esophageal cancer
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Subcutaneous Low Dose Alemtuzumab: Role As a Salvage Therapy in Immune -Mediated Marrow Failure Conditions
No full textAbstract
Aplastic anemia (AA), pure red cell aplasia (PRCA), pure white cell aplasia (PWCA), idiopathic neutropenia (IN) and T cell large granular lymphocytic leukemia (LGL) are bone marrow failure (BMF) conditions unified by immune-mediated pathogenesis leading to cytopenias. Intravenous alemtuzumab, a CD52 monoclonal antibody approved for the treatment of chronic lymphocytic leukemia (CLL) and used for relapsed AA, has a response rate in AA of 37-58%. However, dosing and route was likely based on those used in CLL regimens and resulted in significant immunosuppressive complications.
Here we summarize our experience with sc alemtuzumab given at the maximum dose of total 100 mg as etiologic treatment (either salvage therapy or preferred therapy) to patients with various BMF. We investigated the therapies administered to patients seen at the Cleveland Clinic or at the University of Naples (NCT00895739) between years 2002-2015.
Of 484 patients with BMF conditions (Cleveland: AA: 204, LGL: 174, PRCA: 56; Naples: AA: 24, LGL: 2, PRCA: 14), 65 patients with AA (N=22), PRCA (N=22), LGL (N=18) and 3 cases of IN/PWCA were treated sc alemtuzumab, given according 2 distinct schedules: i. initial dose of 3 mg sc followed by 10 mg once or twice weekly for at least 8 consecutive weeks; ii. 4-5 day dose escalation (3-10-30-30-30 mg) regimen. In both schedules, some patients received a much longer course with maintenance treatment or occasional boosts to prevent or treat relapse. Patients received bactrim and acyclovir prophylaxis, IVIG for hypoglobulinemia and underwent CMV monitoring. The median age of patients was 57.5 years (range: 31-84 years). Alemtuzumab was used as salvage therapy in Cleveland (except for 3 AA cases with contraindication to anti-thymocyte globulin or cyclosporine), whereas in Naples untreated patients were allowed per protocol. As a result, patients had a median of 2 lines of therapy (range: 0-6), had either untreated (35%), relapsed (22%) or refractory (43%) BMF condition. Among the 22 AA patients 12 were untreated, or had relapsed (N=4), or refractory disease (N=6), with concomitant PNH clone in 8/22 patients. LGL patients (N=18) treated with alemtuzumab were younger, had a median of 2 prior therapies, 50% were STAT3 mutants, with comparable degree of cytopenias but excess splenomegaly (60% vs. 38%, p=.012) at presentation, compared to the remainder LGL cohort. Amongst these patients, 18% had relapsed LGL while the rest had refractory disease. PRCA cases treated were either idiopathic (N=18, of whom 3 associated with thymoma) or LGL-associated (N=4); this group was very heterogeneous, including 9 untreated patients (in Naples) and a subgroup of heavily pretreated patients (5 with refractory disease) with a median of 5 prior therapies, with mean hemoglobin of 7.5 g/dL. Among the group of PWCA/IN, one case of PWCA was LGL-associated.
The treatment was well tolerated in 92% of the patients, except in four patients who did not complete treatment course due to adverse events. The main adverse events include infectious complications with 7/65 developing CMV reactivation, 4/65 HSV reactivation, and more rarely other viral reactivation (VZV and HBV, 1/65 each). Two fatal infections were recorded: 1 fungemia (heavily pretreated with other therapies) and 1 JCV-related PML (in a patients also receiving chemotherapy for refractory thymoma).
The overall response rate was 55%; by disease subtype 54% of AA, 44% of LGL, 59% of PRCA and all three cases of PWCA/IN responded. The median time to response in AA was 12 weeks (range: 6-24 weeks), and responses lasted a median of 6 months (range: 2-72 months). In AA, we observed responses in 72% of the cases treated with almetuzumab upfront and 45% of the relapsed/refractory disease. Similarly in PRCA cases, 77% of the alemtuzumab upfront and 46% of the relapsed/refractory disease responded. With a median follow up >4 years, no late treatment-related complication emerged; treatment failures were mostly due to relapses (sometimes refractory to further immunosuppressive treatment), with clonal evolution around 15% (mostly in non-responders).
In summary, low-dose sc alemtuzumab is a reasonable alternative option for patients with BMF conditions, especially in relapsed/refractory cases; patients need to be monitored with a heightened vigilance for infectious complications, as well as for possible recurrence of their underlying disease.
Disclosures
Risitano: Alexion Pharmaceuticals: Other: lecture fees, Research Funding; Alnylam: Research Funding; Rapharma: Research Funding; Novartis: Research Funding
Evaluation of patient (Pt), treatment, and prognostic factors in urinary tract adenocarcinoma.
No full text 408 Background: Adenocarcinoma is a rare histological subtype of urinary tract cancer with limited data regarding risk factors, effectiveness of treatment, and prognostic factors. Methods: To identify prognostic features, we evaluated demographics, treatment, and progression-free and overall survival (PFS, OS) in a retrospective review of 49 pts with adenocarcinoma of the bladder (n=35), ureter (n=1), or urethra (n=13) evaluated at Cleveland Clinic from January 2000 to April 2016. Uni- and multi- variable analyses (UVA, MVA) were used to identify prognostic factors. OS was measured from diagnosis to death and PFS from diagnosis to first of recurrence/progression or death. Results: 25 (51%) pts were women, median age at diagnosis was 62 (33-82), 30 pts (61%) presented with hematuria, and 13/36 (36%) had hydronephrosis. Treatment included cystectomy in 43 pts (88%), neoadjuvant chemotherapy in 3 pts (MVAC, gemcitabine/cisplatin, paclitaxel/cisplatin), adjuvant chemotherapy in 2 pts (gemcitabine), and systemic therapy for advanced or recurrent disease in 6 pts. Overall, 23 pts (47%) recurred/progressed and 31 (63%) died [12 without recurrence/progression]. Estimated median OS and PFS from diagnosis were 38.1 and 24.5 months, respectively. Pts with hydronephrosis at time of diagnosis had shorter PFS (p=0.06) and OS (p=0.007). Among the cystectomy pts, MVA identified pN stage and presence of signet-ring cells or papillary component as the only independent predictors of OS, while pN stage was the only independent predictor of PFS. Combining these factors, 3 prognostic groups for OS were identified (Table). Conclusions: pN stage and morphology are independent predictors of OS in pts with urinary tract adenocarcinoma after radical surgery and can stratify pts into distinct prognostic groups. If validated in larger cohorts, these factors could be used for prognostication, clinical decision making, and trial stratification. [Table: see text] </jats:p
