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Metastases-induced acute pancreatitis is an uncommon condition that has a poor prognosis. Risk factors of acute pancreatitis in known cases have been studied and there is a low survival rate with more than three risk factors on presentation regardless of treatment rendered. These patients should be treated conservatively. Chemotherapy may be attempted in patients with three or fewer poor prognostic signs.

Abstract 1792 Background: With increasing knowledge of cancer pathogenesis and availability of target-specific novel agents, it is expected that therapy will be increasingly tailored to individual biology. This is particularly true in lymphoma because translational research has characterized the molecular basis of the clinical heterogeneity in major lymphoma types, and many new agents are in development. However, a major challenge for clinical studies of specific lymphoma patient subgroups is the real-time testing of patient material in a way that enables prospective targeted clinical trials. Here we describe early patient selection results from a phase 2 trial of newly diagnosed DLBCL that prospectively identifies and enrolls only patients with the non-GCB subtype for randomization to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with or without the proteasome inhibitor bortezomib (VELCADE®). The non-GCB subtype exhibits inferior outcome compared to the GCB subtype after therapy with either CHOP or R-CHOP. Both preclinical and clinical data suggest that inhibition by bortezomib of the nuclear factor-κB pathway, which is frequently activated in non-GCB tumors, specifically benefits these patients (Dunleavy K et al, Blood 2009). Methods: This multicenter phase 2 study is enrolling patients at academic centers (n=10), major hospitals (n=13), and community practices (n=32), providing insight that may be broadly informative with respect to both patient outcomes and future targeted trial design. Obstacles to non-GCB-specific patient selection in this setting include change in standard treatment practice for DLBCL, as well as the challenges of collecting a tumor sample, running the assay, and reporting the subtype in a timely manner. All clinical centers in this study have agreed to release diagnostic pathology blocks to a College of American Pathologists/Clinical Laboratory Improvement Amendments-certified pathology lab for centralized subtyping. The pathology samples are subject to non-GCB testing via a 3-marker immunohistochemistry panel (CD10, bcl-6, mum-1; Hans CP et al, Blood 2004), and the results are reported directly to the clinical site. Results: To date, 45 patients have provided consent and have been subtyped. The mean turnaround time from receipt of sample to reporting of subtype was 1.2 business days (range 1–2 business days). All pathology blocks have been returned to the clinical sites; the mean time elapsed was 4.6 business days (range 4–6 business days). Rapid return of these samples was cited by clinical centers as an important aspect of the study design. There is no indication that pathology block release and central laboratory subtyping has led to delays in patient treatment. Of the 42 patients with results available to date, 5 samples were inevaluable, primarily due to limited tumor cells in the biopsy. Of the 37 samples successfully subtyped, 22 were GCB (59.5%) and 15 were non-GCB (40.5%); this is generally consistent with the ∼50% prevalence of the non-GCB subtype reported in retrospective studies of DLBCL. Fourteen patients have been randomized to therapy. Conclusions: Updates to turnaround time, patient subtype frequency, and enrollment will be presented. These data indicate that many centers are interested in targeted trials that offer new and potentially tailored therapies for their DLBCL patients. These centers can overcome their reluctance to release diagnostic pathology samples and actively enroll patients to randomized studies of frontline therapy. Overall, these results suggest that with careful trial design and attention to key logistical issues, prospective enrichment of specific patient subtypes is feasible in lymphoma. The PYRAMID trial (Clinicaltrials.gov: NCT00931918) continues to enroll patients. Disclosures: Off Label Use: Discussion of Velcade in NHL subtypes other than mantle cell lymphoma is included. Flinn:Millennium Pharmaceuticals, Inc: Research Funding. Noga:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cephalon: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ortho-Centicor: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Papish:Genentech: Consultancy, Honoraria, Speakers Bureau; Sanofi Aventis: Consultancy; MD Advantage: Consultancy; Genomic Health: Speakers Bureau. Reeves:Celgene: Equity Ownership. Parasuraman:Millennium: Employment, Equity Ownership. Corvez:Millennium: Employment, Equity Ownership. Mulligan:Millennium Pharmaceuticals, Inc.: Employment. Leonard:Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria.

ITP is an autoimmune disease characterized by low platelet counts due to increased platelet destruction and inadequate platelet production. It is often a chronic disorder that requires long-term treatment. Current common treatment therapies for chronic ITP include corticosteroids, intravenous immunoglobulins (IVIG), rituximab, and anti-D antibody. Splenectomy may be required for those patients who do not respond or relapse after these medical therapies, or require intolerable doses to achieve safe platelet counts. Few studies have reported treatment pattern of current therapies for ITP. We report results of an international multi-center retrospective and prospective observational study of adult patients receiving treatments and/or splenectomy for chronic ITP. Patients with a diagnosis of ITP were enrolled from 100 community and academic centers. Date of 1st ITP diagnosis, treatments received and medical history were obtained retrospectively from patient chart data. ITP treatments, dose, response, and duration of response were collected prospectively for 12 months. Among 326 patients with ITP studied (mean age=54 years, male 40.2%), 24% received a splenectomy during this study. In patients who were not splenectomized (n=248), 77% received ITP medications with corticosteroids being the most frequently prescribed medication among patients who received 1 type of ITP treatment. IVIG was most frequently prescribed in patients who received 2 types of ITP treatments, and patients were most likely to receive a splenectomy after receiving 2 or more types of ITP treatments (table). In splenectomized patients, the average duration from ITP diagnosis to splenectomy was 2.79 years (n=74, SD=4.42, min=0, max=23.38). Prior to surgery, splenectomized patients were most likely to receive corticosteroids in patients receiving 1 type of treatment, and IVIG in patients receiving 2 types of ITP treatments. Following surgery, splenectomized patients were also most likely to receive corticosteroids in patients receiving 1 type of ITP medication, and rituximab in patients with 2 types of ITP medications. Overall, patients with ITP are exposed to numerous ITP treatments, among which, corticosteroids were most frequently used in both splenectomized and non-splenectomized patients. All patients receiving a splenectomy also required 1 or more ITP treatments following surgery. These results demonstrate that current ITP therapies are limited in efficacy and durability and often lead to patients receiving multiple types of ITP treatments. Novel ITP therapies with better efficacy and durable response are needed. | | | | Splenectomizedb(N=78) | | |:---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ----------------------- | --------------------- | ---------------------- | ----------------------- | -------------------------- | | | ITP Treatments Received | Overall (N=326) | Pre-Splenectomy (N=74) | Post-Splenectomy (N=74) | Non-Splenectomized (N=248) | | aMost frequently used treatment or therapy observed within that subgroup (receiving 1, 2, 3, 4 or more treatments). Percentages (%) are calculated as n divided by the total number of patients within the corresponding subgroup. | | b4 splenectomized patients were excluded from the analysis due to missing data. | | | | 58 (18) | | | 58 (23) | | | 1 | 89 (27) | 23 (31) | 37 (50) | 83 (33) | | Exposure Rate n(%) | 2 | 82 (25) | 15 (20) | 17 (23) | 62 (25) | | | 3 | 49 (15) | 18 (24) | 11 (15) | 27 (11) | | | 4 or More | 48 (15) | 18 (24) | 9 (12) | 18 (7) | | | 1 | Corticosteroids (71%) | Corticosteroids (57%) | Corticosteroids (22%) | Corticosteroids (76%) | | Most Frequently Used Therapy (%)a | 2 | IVIG (39%) | IVIG (73%) | Rituximab (24%) | IVIG (52%) | | | 3 | Splenectomy (45%) | IVIG (56%) | IVIG (27%) | IVIG (52%) | | | 4 or More | Splenectomy (63%) | Rituximab (11%) | Vincristine (22%) | Rituximab (78%)

Background: Lenalidomide (Revlimid®) has demonstrated activity with manageable side effects in relapsed/refractory aggressive non-Hodgkin’s lymphoma (NHL). In the initial pilot study, response to lenalidomide was associated with low tumor burden, long duration from prior rituximab and high absolute lymphocyte count. Aims: To confirm the activity and safety of lenalidomide monotherapy in patients with relapsed/refractory aggressive NHL in an international setting and Determine whether predictors of response identified in the previous study were valid. Methods: Patients with relapsed/refractory aggressive NHL with measurable disease ≥ 2 cm after at least 1 prior treatment regimen were eligible. Patients received 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continued therapy as tolerated or until disease progression. Response and progression were evaluated using the IWLRC methodology. Univariate analyses using Fisher’s exact test were conducted to investigate and characterize associations of prognostic variables with response. Results: Eighteen patients who received lenalidomide were eligible for response assessment as of May 15, 2007. The median age was 66 (43–81) and 17 were male. Histology was diffuse large B-cell lymphoma [DLBCL] (n=11), mantle cell lymphoma [MCL] (n=5) and transformed (n=2). Median time from diagnosis was 2 (0.4–12) years and median number of prior treatment regimens was 3 (1–13). Four patients (22%) exhibited an objective partial response including 2/11(18%) DLBCL and 2/5 (40%) MCL. Five patients had stable disease. Lenalidomide response was associated with low disease burden (29% for < 50 cm2v 0% for ≥ 50 cm2), time from last rituximab to lenalidomide treatment (36% for ≥ 230 days v 0% for < 230 days) and absolute lymphocyte count [ALC] (33% for ≥ 0.6×109/L v 0% < 0.6×109/L). Patients with favorable values for these three prognostic factors (N = 7) had a 57% response rate (compared with a 0% response rate for patients with unfavorable values (N = 11; P = 0.01). Grade 4 adverse events were neutropenia (22%) and thrombocytopenia (11%). Most common Grade 3 adverse events were fatigue (17%), thrombocytopenia (11%) and leukopenia (11%). Conclusion: Lenalidomide has activity in relapsed/refractory aggressive NHL with a favorable safety profile. Initial results from this ongoing study are confirming that patients with low tumor burden, long duration from prior rituximab, and high ALC are more likely to respond.

Introduction: The decision to treat indolent B-cell NHL is often based on progressing bulky disease, worsening symptoms, and increasing hematologic derangement. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with pentostatin (P), purine analog, cyclophosphamide (C), alkylator, and rituximab (R), anti-CD20 monoclonal antibody, represents a promising new approach in the treatment of patients with low grade NHL. Most regimens have utilized fludarabine as the purine analog, but the myelosuppression and immunosuppression of these combinations frequently results in severe infections. We have previously reported our experience with pentostatin and rituximab in a cohort of 133 previously treated and untreated patients with Grade III/IV NHL or CLL (2005 Pan-Pacific Lymphoma Conference). Methods: Fifty-five patients have been enrolled in this study with an expected accrual of 100. Patients are being enrolled through the Pharmatech Research Network. Eligibility criteria allows previously treated and treatment naïve patients diagnosed with bulky stage II or low-grade stage III/IV NHL (REAL classification). Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of 8 cycles. Clinical evaluation was performed after even-numbered cycles. Patients were stratified by disease and by prior treatment status. Results: Forty-seven patients have been eligible for evaluation. NHL patients (median age 64, range 30–84) received a total of 236 cycles (median 6). The ECOG status was 0 (65%) and 1 (33%). The overall objective response rate was 70% (CR 21%, Cru 13%, PR 36%). There were 3 grade 4 neutropenias documented and there was a single grade 4 leukopenia. There were a total of 3 deaths all of which occurred within 30 days of the last dose. The first death was due to a second primary, NSCLC, diagnosed after treatment began. The second death occurred in a 81 year-old female (PR) due to CHF and the last death, due to CAD, occurred in an 84 year-old woman (SD). Conclusions: This immunochemotherapeutic regimen is very active in indolent Grade III/IV NHL and the incidence of significant toxities was extremely low. Future trials evaluating the use of R as maintenance therapy following this PCR regimen may also be warranted with an eye toward increasing the overall survival of patients with NHL. The use of combination therapy in elderly patients should be used with caution due to associated co-morbidities.