ALBERT

Description: Background: The present goal for the treatment of HL is to develop a combined modality therapy with high response rate, disease-free survival (DFS) and overall survival (OSV) with minimal toxicity. Methods: On December 1996, the GATLA started a non randomized protocol for 15 to 75 years old (median 28) patients previously untreated. Patients with clinical stage I, II, IIIA without bulky tumor (〈 10 cm mass or 〈 1/3 thoraxic diameter) (low risk) received 3 cycles of ABVD followed by IFRT 25 Gy to all node areas of more than 2 cm at diagnosis. A total of 46 out of 218 patients (21%) with low risk who failed to achieve complete remission (CR) after 3 cycles of ABVD were included as high risk completing 6 cycles of ABVD. Patients with clinical stage IIIB and IV or all other stages with bulky disease or persistance lymph nodes areas after 3rd cycle of ABVD (high risk) received 6 cycles of ABVD followed by IFRT 30 Gy to residual areas after the third cycle of ABVD or bulky areas at diagnosis. The dose of ABVD was the standard; Adriamycin 25 mg/m2, Bleomycin 10 IU/m2, Vinblastine 6 mg/m2 and Dacarbacine 375 mg/m2 all IV on day 1 and 15 of each 28 days cycles. Patients who achieved partial remission (PR) were salvage with other regimen mainly ESHAP x 3 cycles followed by high dose therapy with autograft rescue. Results: A total of 171 (99%) out of 172 patients with low risk achieved CR. One 74 year old patient died of pneumonia after the third ABVD. A total of 187 (85%) of 219 patients with high-risk achieved CR, 25 PR, and 7 failed to respond (FR) (P

Description: Objetives: Analyze the prognostic significance of CD38 expression compared to other prognostic factors. Patients and methods: We studied retrospectively and prospectively at our institution 160 patients (pts) with diagnostic of CLL who met the diagnostic criteria of National Cancer Institute-Working Group (NCI-WG), 97 men and 63 female with an age range of 33 – 90 years (median 62) diagnosed between January 1989 and December 2003 and evaluated up to June 2004. Sixty nine pts showed CD38 positive cells and 91 were CD38 negative. CD38 expression was determined by flow cytometry defining as a higher expression 〉 7% CD38 positive cells. (Krober A et al. Blood15: 1410–1416.2002). Event Free Survival (EFS) and Overall Survival (OS) were analized according to different characteristics at diagnosis. No. Patients %EFS 72 mo p= %OS 72 mo p= Binet Stage A /B-C 129/31 65/30 0.000 90/92 0.245 Rai Stage 0 /I – II – III – IV 92/68 72/37 0.000 94/94 0.339 TDLI 〈 / ≥ 12 mo 23/126 41/63 0.007 65/100 0.001 Light Chains kappa / lambda 94/66 68/50 0.473 90/95 0.702 CD38 Positive / Negative 69/91 32/82 0.000 81/100 0.000 Statistical significant difference was observed in Binet stage, Rai stage, TDLI and CD38 expression for EFS and in TDLI and CD38 expression for OS. Considering these variables with p value of

Description: Introduction: The present goal standard for the treatment of HL is ABVD plus low doses of IFRT. With the purpose of maintaining a high response rate, event-free survival (EFS) and overall survival (OSV) with minimal toxicity we adapted the number of cycles of ABVD and doses of IFRT to the risk at diagnosis and early response. Methods: From December 1996, up to October 2005 a total of 527 patients, 15 to 75 years old (median 28) previously untreated entered the study. Patients with clinical stage I, II, IIIA without bulky tumor (〈 10 cm mass or 〈 1/3 thoraxic diameter) (low-risk) received 3 cycles of ABVD followed by IFRT 25 Gy to all node areas of more than 2 cm at diagnosis. A total of 55 out of 267 patients (21%) with low-risk who failed to achieve complete remission (CR) after 3 cycles of ABVD were included as high-risk completing 6 cycles of ABVD. Patients with clinical stage IIIB and IV or all other stages with bulky disease or persistance lymph nodes areas after 3rd cycle of ABVD (high risk) received 6 cycles of ABVD followed by IFRT 30 Gy to bulky areas at diagnosis or those areas remaining 〉 2cm after 3 cycles. The dose of ABVD was the standard; Adriamycin 25 mg/m2, Bleomycin 10 IU/m2, Vinblastine 6 mg/m2 and Dacarbacine 375 mg/m2 all IV on day 1 and 15 of each 28 days cycles. Patients who achieved partial remission (PR) were salvage with other regimen mainly ESHAP × 3 cycles followed by high dose therapy with autograft rescue. Results: A total of 211 (99%) out of 212 patients with low-risk achieved CR. One 74 year old patient died of pneumonia after the third ABVD. A total of 277 (87%) of 315 patients with high-risk achieved CR, 28 PR, 9 failed to respond (FR), and 1 died of sepsis (P

Description: Abstract 4820 Background Aplidin (plitidepsin) is a cyclic depsipeptide of marine origin, with activity in relapsed/refractory multiple myeloma and T-cell NHL[1],[2]. Some depsipeptides have been linked to increased cardiac toxicity in the literature[3]. PharmaMar Pharmacovigilance and Clinical Trials Data Management databases were reviewed for cardiac adverse events (CAEs) occurring during clinical trials evaluating plitidepsin as single-agent as of November 2008. Data were analyzed for potential risk factors associations with the occurrence of CAE by univariate and multivariate logistic regression analyses. Results Forty-six of the 578 patients (8.0%) treated had at least one CAE. Eleven patients of 578 (1.9%) had CAE related to plitidepsin, none of them with fatal outcome. CAEs were retrospectively classified into 3 main groups after clinical review of all available data. The most frequent type of CAE were rhythm abnormalities (RA) (n=31; 5.4%), whereas atrial fibrillation (AF)/flutter accounted for most cases (n=15; 2.6%). Most events occurred randomly during plitidepsin treatment. Of note, no cases of life-threatening ventricular arrhythmias have been reported to date. The myocardial injury events (MI) (n=17; 3.0%) included possible ischemic related events as well as non-ischemic events. Finally, miscellaneous events (M) (n=6; 1.0%) included all other cardiac events that did not fit into the aforementioned categories. None of the M events was related to plitidepsin Demographic, clinical and pharmacological variables were explored by univariate and multivariate analysis. Significant association was found with prostate or pancreas cancer diagnosis (p=0.002), known baseline cardiac risk factors (p=0.002), myalgia at baseline (p=0.004), lower hemoglobin levels (p= 0.006) and ≥ grade 2 hypokalemia (p=0.006). Multivariate analysis confirmed all these associations. Importantly, treatment related variables, such as plitidepsin dose, number of cycles or schedule of administration did not result in any statistically significant association. Serial ECGs performed before and after plitidepsin administration (n=136) did not show any relevant effect on QTc interval. None of the PK parameters analyzed (Cmax and AUC from day 0 to day 28) had any significant impact on the probability of developing a CAE. Conclusions CAEs observed to date in plitidepsin trials fit into three clinical categories. The most frequent type observed was AF/atrial flutter, although its incidence was not different to what is reported in age-matched healthy population[4]. All other events were relatively infrequent. No dose-cumulative pattern was observed; moreover, neither plitidepsin dose nor schedule was associated with occurrence of CAEs. Relevant predisposing factors identified in univariate and multivariate analyses were related to patient's baseline and/or disease-related characteristics rather than to drug exposure or treatment-related variables. Data available on 578 adult patients with advanced cancer treated with singe-agent plitidepsin support a favorable cardiac safety profile. Disclosures: Soto-Matos: PharmaMar SAU: Employment. Szyldergemajn:PharmaMar SAU: Employment. Gomez:PharmaMar SAU: Employment. Extremera:PharmaMar SAU: Employment. Miguel-Lillo:PharmaMar SAU: Employment. Alfaro:PharmaMar SAU: Employment. Coronado:PharmaMar SAU: Employment. Lardelli:PharmaMar SAU: Employment. Roy:PharmaMar SAU: Employment. Corrado:PharmaMar SAU: Employment. Yovine:PharmaMar SAU: Employment. Kahatt:PharmaMar SAU: Employment.

Description: Abstract 1767 Background: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of NHL, representing 10–15% of all newly diagnosed cases; their prognosis is poor and optimal therapy is yet to be defined. Most patients (pts) relapse after standard first-line chemotherapy and ultimately die from their disease. Though pralatrexate has been recently FDA-approved for this indication, novel active agents are still needed. From December 2004 to June 2008, 46 adult pts with aggressive non-Hodgkin lymphoma (NHL) were treated in a phase II study aimed at evaluating the activity of plitidepsin. An interim analysis showed responses restricted to pts with PTCL (4/17 vs. 0/29 in pts with B-cell NHL; Fisher's test: p=0.01). Thus, PTCL cohort was expanded. Herein, final results are presented. Patients and methods: As of June 2010, 32 pts were treated with plitidepsin 3.2 mg/m2 i.v. infusion over 1-h on days 1, 8 and 15 q4wk. Twenty-nine pts are evaluable for efficacy. Median number of previous regimens was 2 (range, 1–6), including prior stem cell transplantation in 9 pts (28%). Histology: PTCL, NOS 16, anaplastic large-cell 4, angioimmunoblastic 9 and NK/T nasal type 3. Twenty-three pts were male, median age was 57 y (30-80) and ECOG: 0 (14 pts), 1 (12 pts) and 2 (6 pts). Results: Two CR and 4 PR were observed, for a 20% objective response rate (95% CI, 8%-39%). Median duration of response was 2.2 months (range, 1 – 28). Median progression-free survival was 1.6 months (95% CI, 1 – 3) and median overall survival was 10.2 months (95% CI, 4 – 24). Toxicity, particularly haematological, was mild. Two patients developed G3, and 2 G4 neutropenia, and 1 pt G3, and 2 G4 thrombocytopenia. Transient and reversible G3 ALT or AST elevations occurred in 7 and 4 pts, respectively, with no patients experiencing G4 events. Clinical toxicities were mainly G1-2 muscular weakness and myalgia in 14% of pts, and G1-2 fatigue, nausea and vomiting in 21%, 28% and 17% of patients, respectively. Conclusions: Plitidepsin has activity, with an acceptable safety profile in non-cutaneous relapsed/refractory PTCL patients. Remarkably, lack of hematologic toxicity makes plitidepsin an ideal agent either for treating patients with poor bone marrow reserve or combining it with other active agents. A combination of plitidepsin with gemcitabine is currently being explored in this patient population. Disclosures: Szyldergemajn: PharmaMar SAU: Employment. Corrado:PharmaMar SAU: Employment. Extremera:PharmaMar SAU: Employment. Vandermeeren:PharmaMar SAU: Employment.