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Few published reports have documented the value of SMBG on glycemic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), and no reports have evaluated predominantly African American patients who are at high risk for NIDDM and associated complications. In this study a 13- item survey was given to 98 patients with NIDDM to assess the frequency of self-monitoring of blood glucose (SMBG) and its impact on glycemic control. Sixty- one potients performed SMBG and 37 did not. More SMBG testers were taking insulin compared with the nontesters. GHb was comparable between groups. Amongthe testers there was no difference in mean GHb values based on the frequency of SMBG. Most testers performed SMBG before meals (93%) and recorded their values (85%); many had difficulty obtaining a good blood sample (30%). The most common reason for not testing was cost of supplies (77%). Performance of SMBG in these NIDDM patients was not associated with better glycemic control. Cost was a prohibitive factor for the nontesters.

Flinn: Celgene Corporation: Research Funding. Boccia:Incyte Corporation: Honoraria. Berdeja:Array: Research Funding; Curis: Research Funding; Onyx: Research Funding; Abbvie: Research Funding; Acetylon: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Janssen: Research Funding; BMS: Research Funding; MEI: Research Funding; Takeda: Research Funding.

Introduction: Rituximab and bendamustine combination regimens have demonstrated high activity in non-Hodgkin's lymphoma (NHL). Phase III trials evaluating bendamustine plus rituximab as first-line therapy for patients (pts) with indolent and mantle cell lymphoma have shown equivalent or superior results when compared to R-CHOP or R-CVP as first-line treatment for indolent lymphoma. The proteasome inhibitor, bortezomib, has shown substantial activity in multiple myeloma and has demonstrated synergy and/or ability to overcome resistance to a variety of current and investigational treatments for lymphoma. A Phase II study of the combination of bendamustine, bortezomib, and rituximab (BBR) in relapse/refractory indolent and mantel cell NHL pts resulted in an ORR of 83% and 47% 2yr PFS (Friedberg, Blood 2011). This Phase II trial evaluated the activity of BBR in patients with previously untreated low-grade lymphoma.

Rituximab and bendamustine combination regimens have demonstrated high activity in non-Hodgkin's lymphoma (NHL). A phase III trial compared bendamustine plus R-CHOP as first-line treatment for follicular, indolent, and mantle cell lymphoma (Rummel ASH 2009). Bendamustine plus rituximab had an overall response rate of 94% and a complete remission rate of 40% compared to 94% and 31%, respectively, for R-CHOP. Phase III trials evaluating bendamustine plus rituximab as first-line therapy for patients (pts) with indolent and mantle cell lymphoma have shown equivalent or superior results when compared to R-CHOP or R-CVP as first-line treatment for indolent lymphoma. Bortezomib is a small molecule proteasome inhibitor that has shown substantial activity in multiple myeloma and lymphoma. Pre-clinical studies demonstrate significant synergy and/or ability to overcome resistance to a variety of current and investigational treatments for lymphoma. This trial evaluated the activity of bendamustine, bortezomib, and rituximab (BBR) in patients with previously untreated low-grade lymphoma.Eligible patients had histologically-confirmed follicular center cell (FCC) lymphoma (grade 1 or 2), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), or lymphoplasmacytic lymphoma (LPL); lymph node biopsy containing CD20+ B-cells; Ann-Arbor Stage 2, 3, or 4 disease; no previous systemic treatment for lymphoma; bi-dimensional measurable disease with at least 1 lesion measuring > 2.0 cm in a single dimension; ECOG PS 0–2. Treatment for all patients was given in 28-day cycles for a maximum of 6 cycles. Patients received rituximab 375 mg/m2 IV on days 1, 8, and 15 of cycle 1 (cycles 2–6, rituximab only on day 1); bendamustine 90 mg/m2 IV on days 1 and 2; and bortezomib 1.6 mg/m2IV on days 1, 8, and 15. Response evaluations were performed after cycle 3 and cycle 6. Patients were permitted to begin maintenance treatment with rituximab 6 months after completion of study treatment and after 6-month follow-up assessments have been conducted.Between 1/2010 and 11/2011, 55 patients were enrolled with a median age of 62 years (range 30–89). Fifty one percent were male, 85% stage III or IV. Diagnoses were: FCC, 38pts (69%); MZL, 8pts (15%); SLL, 5pts (9%) and LPL, 4pts (7%). The median follow-up is 13 months (range: 6–26). At the time of this analysis, 78% of pts had completed 6 cycles of BRR, and 56% had continued to maintenance rituximab. Two pts remain in the first 6 cycles of BRR. Five pts (9%) discontinued treatment due to toxicity (1pt G2 neuropathy, 1 pt G2 atrial fibrillation, 1 pt G3 pancreatitis, 1 pt G3 diarrhea, 1pt G2 rash). The remaining 5 pts discontinued prematurely (1pt death due to stroke, 1pt wound complication, 1 pt lost to follow-up, 2 pts off due to request). Objective response was achieved in 89% of pts; 26pts (47%) complete response, 23pts (42%) partial response, 2pts (4%) stable disease, and 4pts (7%) unevaluable at the time of this analysis. Related grade 3/4 hematologic toxicities were: neutropenia (25%), febrile neutropenia (2%), thrombocytopenia (5%), and anemia (4%). We observed no grade 4 treatment related non -hematologic adverse events, the most common grade 3 were neuropathy (9%), diarrhea (7%), fatigue (7%), constipation (5%), and rash (5%). Time-to-event data are immature and will be the subject of a later analysis. At the time of data cut-off, 3 pts (5.5%) had progressed or relapsed and 3pts (5.5%) had died.BBR was well tolerated and produced high CR and OR rates. Toxicities including neuropathy were modest. Further study of this regimen in patients with previously untreated lymphoma is warranted.Off Label Use: Off-label bendamustine and bortezomib in first-line treatment for lymphoma. Boccia:Cephalon: Research Funding.

Protein kinase C β (PKCβ) is critical for B-cell signaling and survival. Over-expression of PKCβ is implicated in the pathogenesis of follicular lymphoma (FL). Enzastaurin (ENZ), an oral serine/threonine kinase inhibitor, targets the PKCβ and PI3K/AKT pathways to inhibit tumor cell proliferation, induce apoptosis, and suppress tumor-induced angiogenesis. Reported here are the final clinical and correlative study results from a phase II study.This was an open-label, single-arm, study of patients (pts) with hiastologically confirmed grade 1/2 and stage III/IV measurable FL. Pts were either chemonaive or relapsed after 1 chemotherapy regimen or single-agent rituximab. Pts received 500 mg oral ENZ once daily (1125-mg loading dose on D1) ≤ 3 years or until progression, withdrawal, or toxicity. The primary endpoint was response rate (RR). Secondary objectives included progression-free survival (PFS), duration of response (DoR), and safety. Pre-treatment samples were used for correlative research. Staining was performed for BCL2, BCL6, CD10, Ki67, FOXP1, FOXP3, CD20, MUM1, CD68, and PD1 expression. ENZ-specific biomarkers investigated by immunohistochemistry (IHC; standard H scores range 0–300) included PKCβ2, PTEN, pS6, pGSK3β, and pCREB. Logistic/Cox regression determined the statistical correlation between clinical outcomes (RR or PFS) and IHC for each marker. All tests of association were conducted at a 2-sided α = 0.05.Sixty-six pts (23 male, 43 female; median age 62 years \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(3382\) \end{document}) were enrolled. Based on FL International Prognostic Index, 12% had low-risk disease (0-1 risk factors [RF]); 55%, intermediate-risk disease (2 RFs); and 33%, high-risk disease (3-5 RFs). Forty-six pts (69.7%) were chemonaive and 20 pts (30.3%) had ≥ 1 prior chemotherapy. The median overall exposure was 10.8 months (mo; 1–57 mo). Of 58 pts who received ≥1 dose of ENZ, 2 (3.4%) had complete response, and 15 (25.9%) had partial response (overall RR = 29.3%). The median PFS was 15.2 mo (95% confidence interval [CI] 11.1–25.7 mo). DoR median was 20.5 mo (95% CI 9.1–31.5 mo). Seven pts (10.6%) discontinued treatment due to adverse events (AEs), of which 5 (7.6%) were possibly drug related: bronchitis, prolonged QTc interval, abdominal distention, colitis, and skin rash. Four pts (6.1%) had drug-related serious AEs: grade (Gr) 3 bronchitis, Gr 2 vision, Gr 2 diarrhea, Gr 2 pancreatitis. There were no drug-related deaths. To date, 5 pts remain on treatment and have been on treatment 3.5–5 years.Tumor tissue was obtained from 28 pts. Patient demographics and overall RR were well balanced between protocol and correlative study populations. No significant associations with RR or PFS were observed for any FL-specific markers. Significant associations were observed between low cytoplasmic PKCβ2 and increased RR (median H score cutpoint 151.5, odds ratio (OR) [95%CI] = 0.027 [0.001-0.656], p=0.027) (Table 1, Figure 1). Significant associations were also observed between PFS and both cytoplasmic PKCβ2 and cytoplasmic pS6 using median H score cutpoint (Table 1).ENZ has clinical activity and is well tolerated in pts with grade 1/2 FL. Low cytoplasmic PKCβ2 was significantly associated with increased RR and longer PFS; high cytoplasmic pS6 was significantly associated with longer PFS. The correlative results are hypothesis generating given the study's size and nonrandomized nature.Hermann: Eli Lilly and Company: Research Funding. Hsi:Eli Lilly and Company: Research Funding. Hamid:Eli Lilly and Company: Employment. Myrand:Eli Lilly and Company: Employment. Lin:Eli Lilly and Company: Employment. Thornton:Eli Lilly and Company: Employment. Shi:Eli Lilly and Company: Employment. Nguyen:Eli Lilly and Company: Employment.

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