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Abstract Abstract 728 Background: LM, an antibody-drug conjugate (ADC), is designed to specifically kill CD56+ cancer cells and contains a potent maytansinoid cytotoxic agent (DM1) attached to a CD56-targeting antibody. MM shows CD56 expression in >70% of cases. LM has demonstrated single agent clinical activity and an acceptable safety profile in relapsed/refractory (rel/ref) MM patients. Preclinical studies showed enhanced anti-MM activity when LM was combined with Len/Dex. To further study the safety and efficacy of LM in combination with Len/Dex, a phase I study was conducted in rel/ref patients. This abstract reports updated results on the safety and efficacy of LM/Len/Dex and preliminary results on the pharmacokinetics (PK) and immunogenicity studies. Methods: Primary study objectives were to determine the safety, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), anti-MM activity and PK of LM in combination with standard oral (PO) doses of Len (25 mg po, daily on days 1–21) and Dex (40 mg po on D 1, 8, 15, and 22) in CD56+ rel/ref MM patients who have received at least 1 prior therapy. LM was given intravenously (IV) on D 1, 8, and 15 on a 28-day cycle. Dose escalation was conducted in new cohorts of patients to define the MTD, which was then further evaluated in a dose-expansion cohort. Adverse events (AEs) were assessed using CTCAEv3 criteria, and dose-limiting toxicity (DLT) determination was based on the occurrence of AEs that were probably or definitely attributed to the study regimen. Efficacy was assessed using the International Myeloma Working Group (IMWG) criteria. Enrollment has completed and 16 patients remain on study. Results: Forty-four patients were enrolled, 41 are currently evaluable for safety and 32 are evaluable for efficacy. The median number of prior therapies was 2 (range 1–11), 62% of patients had prior Len exposure and 33% were Len refractory. LM doses of 75 (N = 11), 90 (N=4), and 112 (N =6) mg/m2 were evaluated in the dose-escalation phase. The most common AE was peripheral neuropathy (PN), which occurred more frequently at higher LM doses (55% at 75 mg/m2 and 100% at 90 and 112 mg/m2); Grade 3 PN was seen only in patients treated at 90 mg/m2 or above. PN emerged, in most cases, in cycles >3 and was manageable with LM dose modification. During dose escalation, 1 patient experienced Grade 4 neutropenia and hyperuricemia. The 75 mg/m2 LM dose was considered the MTD based on overall tolerability and the lower incidence of PN observed, and was further tested to determine its suitability as the RP2D in the dose expansion portion of the study (N=23 patients, 19 patients available for safety evaluation). Grade 1–2 PN occurred in 8 patients (42%) and grade 3 PN was observed only in 1 pt in the dose-expansion cohort. Two patients developed grade 3 tumor lysis syndrome (TLS). Other grade 3 AEs reported in 1 patient each (5%) in the dose-expansion cohort consisted of neutropenia, thrombocytopenia, anemia, hemolytic anemia, and LDH increase. Efficacy was observed across all dose levels and the overall response rate (ORR) was 59%, including 1 patient each with stringent complete response (sCR) and complete response (CR), 8 patients with very good partial remission (VGPR), and 9 patients with partial remission (PR). No immunogenicity against the antibody (HAHA) or DM1 component (HADA) of LM was detected. PK results from 18 patients treated at 75 mg/m2 indicate LM Cmax and exposure in this combination regimen is consistent with LM monotherapy. Conclusions: Based on all available safety data, 75 mg/m2 was considered the RP2D. LM at 75mg/m2 in combination with Len and Dex has shown objective evidence of clinical activity with an acceptable safety profile. Disclosures: Off Label Use: Lorvotusumab mertansine is not FDA approved for treatment of multiple myeloma alone or in combination with lenalidomide and dexamethasone as is investigated in this trial. Running:ImmunoGen, Inc.: Employment. Murphy:ImmunoGen, Inc.: Employment. Guild:ImmunoGen, Inc.: Employment. Carrigan:ImmunoGen, Inc: Employment. Ladd:ImmunoGen, Inc.: Employment. Wolf:ImmunoGen, Inc.: Employment, Equity Ownership. O'Leary:ImmunoGen, Inc.: Employment. Ailawadhi:Millenium Pharmaceuticals: Speakers Bureau.

AbstractAimSurgery aims to prevent cancer‐related morbidity for patients with ulcerative colitis (UC) associated dysplasia. The literature varies widely regarding the likelihood of dysplastic progression to higher grades of dysplasia or cancer. The aim of this study was to characterize the likelihood of the development of colorectal cancer (CRC) of patients with UC‐associated dysplasia who chose to defer surgery.MethodA retrospective review was carried out of patients undergoing surgery for UC at the Mayo Clinic, who were diagnosed to have dysplasia between August 1993 and July 2012. The relationships between grade of dysplasia, time to surgery and the detection of unsuspected carcinoma were investigated.ResultsIn all, 175 patients underwent surgery at a median of 4.9 (interquartile range 2.5–8.9) months after a diagnosis of dysplasia. Their median age was 52 (interquartile range 43−59) years. An initial diagnosis of indeterminate dysplasia was not associated with CRC [0/23; 17.7 (8.1−29.6) months]. Thirty‐six patients who had an initial diagnosis of dysplasia progressed from indeterminate to low‐grade dysplasia [24.2 (11.0−30.4) months]. Low‐grade dysplasia was associated with a 2% (1/56; T2N0M0) risk of CRC when present in random surveillance biopsies and a 3% (2/61; T1N0M0, T4N0M0) risk if detected in endoscopically visible lesions [7.4 (5.2−33.3) months]. Eighteen patients progressed from indeterminate to high‐grade dysplasia [19.1 (9.2−133.9) months]. Seventeen patients progressed from low to high‐grade dysplasia [11.0 (5.8−30.1) months]. None of the patients with high‐grade dysplasia (0/35) progressed to CRC [4.5 (1.7−9.9) months].ConclusionDysplasia was associated with a low incidence of node negative CRC if surgery was deferred for up to 5 years. These findings may help inform the decision‐making process for asymptomatic patients who are having to decide between intensive surveillance or surgery for UC‐associated dysplasia.

AbstractExtended lymphadenectomy has gained considerable attention as an adjunct to conventional colon cancer surgery with the hope that it may potentially decrease local recurrence rates and improve cancer‐specific outcome measures. Despite the enthusiasm surrounding these techniques, it is difficult to establish any additional survival benefit associated with more comprehensive lymphadenectomy strategies when these are performed in addition to conventional colon cancer surgery. Furthermore, these techniques remain unproven by large randomized clinical trials. The appropriate indications for performing extended lymphadenectomy also remain unclear, and there is a lack of standardization with regard to surgical technique. Moreover, there are a number of confounding factors that frequently receive little attention when oncological outcome measures are reported following extended lymphadenectomy in the setting of colon cancer. The purpose of this review is to outline these confounding issues and discuss their impact on reports describing cancer‐specific outcome measures following the use of extended lymphadenectomy techniques. Furthermore, this review proposes that in light of the available published evidence, the role of radical lymphadenectomy is currently unproven, with large randomized clinical trials required in the future to determine whether there is a survival benefit for colon cancer patients.

Abstract Mesenchymal Stem Cells (MSCs) have the ability to migrate specifically to tumours in vivo, and coupled with their capacity to bypass immune surveillance, are potentially attractive vehicles for tumor-targeted delivery of therapeutic agents. The aim of this study was to determine the potential of MSC-mediated expression of the sodium iodide symporter (NIS) for in vivo imaging and therapy of breast tumours. Expression of NIS allows cells to concentrate radionuclides including technetium-99m (Tc-99m) and 131-Iodine (131-I). This could potentially support imaging of NIS-expressing MSCs following engraftment, and 131-I therapy of surrounding tumour tissue based on the bystander effect of the radionuclide. Methods: Tumor bearing animals (MDA-MB-231 flank) were given an intravenous or intratumoral injection of NIS expressing human MSCs (MSC-NIS), followed by imaging 3, 7, 10 or 14 days later. Imaging was performed using a Bazooka SPECT γ-camera, following intraperitoneal injection of 2mCi/74MBq Tc-99m. Following imaging, animals were sacrificed and organs harvested for analysis of hNIS expression by RQ-PCR. A second group of animals received an intraperitoneal injection of 1mCi/37MBq 131-I or saline (controls) 14 days following intratumoral or intravenous injection of MSC-NIS, and tumour volume was tracked for 8 weeks. Results: Bazooka SPECT imaging of animals revealed uptake of tracer (Tc-99m) in the mouse thyroid/salivary glands and stomach, representing native NIS expression. Following injection of MSC-NIS, an image of animal intestines was also observed at D3, with a weak image of the tumour also visible. By Day14, uptake of tracer was visible at the site of the tumour with no significant image of non-target tissue observed. Expression of hNIS in harvested organs supported the imaging data, with hNIS detected in the intestines, heart, lungs and tumour at early timepoints. While NIS expression depleted in non-target tissues by D7, gene expression persisted at the tumour site. Based on imaging/biodistribution data, animals were given a therapeutic dose of 131-I 14 days following MSC-NIS injection to avoid toxicity to non-target organs. No adverse effect of injection of MSC-NIS or radionuclide was observed. Tracking of tumour volume revealed a significant reduction in tumour growth in animals that had received an intravenous injection of 131-I 14days following MSC-NIS injection (Mean ± SEM, 236 ± 62mm3 versus 665 ± 204 mm3 in controls). Following intratumoral injection of MSC-NIS + 131-I, although tumour size was reduced compared to controls (472 ± 80 mm3), the difference in volume was not significant. Conclusion: The ability to non-invasively track MSC migration and transgene expression in real time prior to therapy is a major advantage to this strategy. This promising data supports the viability of this approach as a novel therapy for metastatic breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5392. doi:10.1158/1538-7445.AM2011-5392

OBJECTIVE To compare the compliance with diabetes care performance indicators by diabetes specialists using a diabetes electronic management system (DEMS) and by those using the traditional paper medical record. RESEARCH DESIGN AND METHODS A DEMS has been gradually introduced into our subspecialty practice for diabetes care. To assess the value of this DEMS as a disease management tool, we completed a retrospective review of the medical records of 82 randomly selected patients attending a subspecialty diabetes clinic (DC) during the first quarter of 1996. Eligible patients were defined by the suggested criteria from the American Diabetes Association Provider Recognition Program. During the first quarter of 1996, ∼ one half of the providers began using the DEMS for some but not all of their patient encounters. Neither abstractors nor providers were aware of the intent to examine performance in relationship to use of the DEMS. RESULTS Several measures were positively influenced when providers used the DEMS. The number of foot examinations, the number of blood pressure readings, and a weighted criterion score were greater (P < 0.01) for providers using the DEMS. There was evidence, although not statistically significant, for lower mean diastolic blood pressures (P = 0.043) in patients and for number of glycated hemoglobins documented (P = 0.018) by users of the DEMS. CONCLUSIONS Performance and documentation of the process of care for patients with diabetes in a subspecialty clinic are greater with the use of a DEMS than with the traditional paper record.