Renal safety of zoledronic acid with thalidomide in patients with myeloma: a pharmacokinetic and safety sub-study

BACKGROUND: Cases of impaired renal function have been reported in patients who had been treated with both zoledronic acid and thalidomide for myeloma. Hence, we conducted a safety study of zoledronic acid and thalidomide in myeloma patients participating in a trial of maintenance therapy. METHODS: Twenty-four patients who were enrolled in a large randomized trial of thalidomide vs no thalidomide maintenance therapy for myeloma, in which all patients also received zoledronic acid, were recruited to a pharmacokinetic and renal safety sub-study, and followed for up to 16 months. RESULTS: No significant differences by Wilcoxon rank-sum statistic were found in zoledronic acid pharmacokinetics or renal safety for up to 16 months in patients randomized to thalidomide or not. CONCLUSION: In myeloma patients receiving maintenance therapy, the combination of zoledronic acid and thalidomide appears to confer no additional renal safety risks over zoledronic acid alone

Parental occupational exposures and the risk of childhood sporadic retinoblastoma: a report from the Children's Oncology Group.

OBJECTIVES:We examined associations between parental occupational chemical exposures up to 10 years before conception and the risk of sporadic retinoblastoma among offspring. METHODS:In our multicentre study on non-familial retinoblastoma, parents of 187 unilateral and 95 bilateral cases and 155 friend controls were interviewed by telephone. Exposure information was collected retroactively through a detailed occupational questionnaire that asked fathers to report every job held in the 10 years before conception, and mothers 1 month before and during the index pregnancy. An industrial hygienist reviewed all occupational data and assigned an overall exposure score to each job indicating the presence of nine hazardous agents. RESULTS:We estimated elevated ORs for unilateral and bilateral retinoblastoma among offspring of fathers who were exposed to polycyclic aromatic hydrocarbons or paints in the 10 years before conception. However, only for exposure to paints did confidence limits exclude the null for bilateral disease (OR: 8.76, 95% CI: 1.32 to 58.09). Maternal prenatal exposure to at least one of the nine agents was related to increased risk of unilateral disease in their children (OR: 5.25, 95% CI: 1.14 to 24.16). Fathers exposed to at least one of the nine agents and who were ≥30 years of age were at increased risk of having a child diagnosed with bilateral retinoblastoma (OR: 6.59, 95% CI: 1.34 to 32.42). CONCLUSIONS:Our results suggest a role for several hazardous occupational exposures in the development of childhood retinoblastoma

Pomalidomide Alone or in Combination With Low Dose Dexamethasone As Maintenance Following Induction With Pomalidomide And Low Dose Dexamethasone In Relapsed And Refractory Myeloma (Allg Mm14

Background: Whilst the addition of dexamethasone to upfront therapy with Immunomodulatory (IMiD®) agents is important to mediate rapid reduction in disease burden, preliminary findings suggest that the NK stimulatory effects of IMiD® compounds are best harnessed without the co-administration of dexamethasone, and may be especially effective in the setting of minimal disease burden (in the maintenance setting for example) when some inherent immune recovery has occurred. However this has yet to be confirmed in a prospective clinical trial. Aims: To evaluate the effect of maintenance with POM alone (Arm 1) versus POM-LoDEX (Arm 2) on progression free survival (PFS), overall survival (OS), and kinetics of response (overall response rate (ORR)) in relapsed myeloma (MM) patients refractory to lenalidomide (R-LEN) demonstrating stable disease (SD) or better following salvage treatment with pomalidomide (POM) and low dose dexamethasone (LoDEX) induction. Methods: Multicentre, open-label, randomized phase 2 study of relapsed RLEN patients who had received>2 prior lines of therapy. POM 4mg days 1-21 (28 day cycle) was administered alone or in combination with LoDEX (40mg weekly) as maintenance following an induction with 4 cycles of POM and LoDEX. Treatment continued until toxicity or progression. Peripheral blood samples for immune studies were collected pre-induction and prior to cycles 1, 3, 6 and 10 of maintenance. Results: 154 patients from 11 sites were enrolled on to the study (M:F 80:74), with a median age of 67 years (range 35-88). Median number of prior lines of therapy was 4.5 (2-14). All patients had failed LEN (100%), 127 (82.5%) were also refractory to bortezomib (double refractory) and 94 (61%) had received a prior autologous stem cell transplant. 72 (47%) patients achieved SD or better with POM-LoDEX induction and were randomised, 35 to POM (Arm 1) and to 37 to POM-LoDEX (Arm 2). After a median follow-up of 19 months, median PFS for all patients from study entry was 4.2m (IQR 2.1 – 8.6m). PFS for randomised patients (from time of randomisation) was 2.7m for POM (arm 1) versus 5.6 for POM-LoDEX (arm 2) (p=0.39). The PFS hazard rate for Arm 2 was relatively constant compared to Arm 1 which started with a hazard rate double that of Arm 2 but dropped to less than half of the rate in Arm 2 by 15 months, suggesting that with longer follow-up, there may be an emergent advantage to maintenance with POM versus POM-LoDEX (Figure 1.). Median OS for all patients from study entry was 13.2m (IQR 6.3-26.8m). For randomised patients, median OS (from time of randomisation) was 19m for POM (Arm 1) versus 13.7m for POM-LoDEX (Arm 2) (p=0.41). ORR (≥PR) for all patients was 45.5% [CR=5 (3.3%), VGPR=13 (8.4%), PR=52 (33.8%)]. Clinical benefit rate (CBR) (≥MR) was 55.2% [MR=15 (9.7%)]. Summary/Conclusions: In patients with relapsed myeloma, after initial disease control/debulking is achieved with POM - LoDEX, induction, maintenance with single agent POM may be more effective for sustaining disease control than continuation of POM-LoDEX. Correlative studies are currently underway to further investigate the immunological mechanisms behind this observation

MOA-2010-BLG-328Lb: a sub-Neptune orbiting very late M dwarf ?

We analyze the planetary microlensing event MOA-2010-BLG-328. The best fit yields host and planetary masses of Mh = 0.11+/-0.01 M_{sun} and Mp = 9.2+/-2.2M_Earth, corresponding to a very late M dwarf and sub-Neptune-mass planet, respectively. The system lies at DL = 0.81 +/- 0.10 kpc with projected separation r = 0.92 +/- 0.16 AU. Because of the host's a-priori-unlikely close distance, as well as the unusual nature of the system, we consider the possibility that the microlens parallax signal, which determines the host mass and distance, is actually due to xallarap (source orbital motion) that is being misinterpreted as parallax. We show a result that favors the parallax solution, even given its close host distance. We show that future high-resolution astrometric measurements could decisively resolve the remaining ambiguity of these solutions

Ocular adnexal diffuse large B-cell lymphoma: local disease correlates with better outcomes

Purpose: To describe the clinical, immunohistochemical and prognostic features, as well as outcomes of a large series of patients with orbital and periorbital diffuse large B-cell lymphoma (DLBCL). Design: This study is a multicentre, retrospective non-comparative consecutive case series. Methods: The setting for this study was institutional. A total of 37 consecutive patients identified from the institutions' databases with periorbital and orbital DLBCL were enrolled in the study. A retrospective chart review was used for observation. The main outcome measures were patient demographics, clinical features, imaging, immunohistochemical and histopathological data, treatments administered, and survival. Results: A total of 20 out of 37 cases (54.1%) represented localised periorbital disease (group L), 11 of 37 (29.7%) had systemic disease at presentation with periorbital disease (group S1), and 6 of 37 (16.2%) had previous history of systemic lymphoma (group S2). In all, 28 out of 30 (93.3%) patients were CD20+, 5 of 25 (20%) were CD3+, and 11 of 11 (100%) were CD79a+ (varying denominators reflect the different numbers of patients tested). A total of 25 out of 32 patients (78.1%) received chemotherapy, 14 (43.8%) received rituxmab plus chemotherapy, and 19 (59.3%) received radiotherapy. Nine deaths occurred, one in group L (not lymphoma related), six in group S1, and two in group S2. Five-year Kaplan–Meier survival estimates were 55.9% for all cases, 90.9% for group L, 36.0% for group S1, and 0% for group S2. One-year progression-free survival estimates in groups S1 and S2 combined were 58.3% for patients treated with rituximab and 28.6% for those who were not. Conclusions: To our knowledge, this report represents the largest series of patients with periorbital and orbital DLBCL in the literature. The difference in survival between groups L, S1 and S2 was striking, reflecting the grave prognosis of systemic DLBCL, but conversely the relatively optimistic outlook for patients with localised disease. Rituximab plus chemotherapy may be associated with increased survival.S.N. Madge, A. McCormick, I. Patel, E. Hatef, V. Menon, V.C. Prabhakaran, L. Irion, R. Bonshek, S. Honovar, B. Leatherbarrow, B. Esmaeli and D. Selv