Pomalidomide is a distinct immunomodulatory agent with significant activity in relapsed/refractory multiple myeloma (RRMM). The optimal treatment schedule in patients with RRMM who have received ...multiple lines of treatment, including bortezomib and lenalidomide, is 4 mg/day on days 1–21 of a 28-day cycle in combination with weekly low-dose dexamethasone. Improved responses and outcomes relative to traditional therapies continue to be confirmed in recently completed and ongoing trials. Pomalidomide exhibits direct tumoricidal, immunomodulatory, anti-angiogenic and anti-inflammatory activities, which facilitate combination therapy with agents with complementary mechanisms of action, resulting in greater anti-myeloma effects than single-agent therapy or previous combination therapies. For example, in combination with proteasome inhibitors and traditional chemotherapeutic agents in doublet or triplet regimens, pomalidomide provides high rates of durable response, and represents an important new treatment option for patients with RRMM requiring effective new therapies. Additionally, pomalidomide maintains its efficacy and tolerability profile in difficult-to-treat patients, including the elderly, patients with poor cytogenetics and those with renal impairment. This review summarises the clinical development of pomalidomide and discusses this effective agent for the treatment of patients with RRMM in the context of current myeloma treatment options, as well as potential future directions to further improve patient outcomes.
Although the written component of the Royal College of Physicians and Surgeons of Canada (RCPSC)internal medicine examination is important for obtaining licensure and certification as a specialist, ...no methods exist to predict a candidate's performance on the examination.
We obtained data from 5 Canadian universities from 1988 to 1998 in order to compare raw scores from the American Internal Medicine In-Training Examination (AIMI-TE) with raw scores and outcomes (pass or fail) of the written component of the RCPSC internal medicine examination.
Mean scores on the AIMI-TE correlated well with scores on the RCPSC internal medicine written examination for all postgraduate years (r = 0.62, r = 0.55 and r = 0.65 for postgraduate years 1, 2 and 3 respectively). Scores above the 50th percentile on the AIMI-TE w/ere predictive of a low failure rate (< 1.5%) on the RCPSC internal medicine written examination, whereas scores at or below the 10th percentile were associated with a high failure rate (about 24%).
Candidates who are eligible to take the written component of the RCPSC certification examination in internal medicine can use the AIMI-TE to predict their performance on the Canadian examination. The AIMI-TE is a useful test for residents in all levels of training, because the examination scores have a strong relation to expected performance on the Canadian examination for each year of postgraduate training.
The rate at which water-soluble chemotherapeutic drugs enter brain tumors can be extremely variable. The ability to measure or predict the rate of drug entry may have an important role in treatment. ...We have developed a method that uses information from contrast-enhanced computed tomographic scans to measure quantitatively the rate of transcapillary transport of iodinated compounds in brain tumors. In a group of 10 patients with brain tumors, we obtained serial measurements of tissue (Am) and arterial plasma (Cp) iodine concentration from timed computed tomographic scans done over 30 minutes, after intravenous infusion of meglumine iothalamate (Conray-60). These measurements were analyzed with a two-compartment pharmacokinetic model and nonlinear least-squares regression methods to obtain K1, a blood-to-tissue transfer constant; k2, a tissue-to-blood rate constant; and Vp, tissue plasma vascular volume. Images of K1, k2, and Vp were reconstructed after calculating these values for each 0.8 x 0.8 x 5-mm volume element of the original data. Mean whole tumor K1 values varied from 2.0 mu 1 gm-1 min-1 in a thalamic astrocytoma to 33.9 mu 1 gm-1 min-1 in a glioblastoma multiforme. The value of k2 varied from 0.034 to 0.108 min-1, and Vp varied from 2.4 to 7.9 ml 100 gm-1. In tumor-free brain, the K1 of meglumine iothalamate was 2.9 mu 1 gm-1 min-1; k2 was 0.058 min-1; and Vp was 2.1 ml 100 gm-1.
Abstract Bortezomib (V), lenalidomide (R), cyclophosphamide (C) and dexamethasone (D) are components of the most commonly used modern doublet (RD, VD) or triplet (VRD, CVD) initial induction regimens ...prior to autologous hematopoietic cell transplantation (AHCT) for multiple myeloma (MM) in the US. In this study we evaluated 693 patients receiving “upfront” AHCT after initial induction therapy with modern doublet or triplet regimens using data reported to the Center for International Blood and Marrow Transplant Research from 2008-2013. Analysis was limited to those receiving a single AHCT after one line of induction therapy within 12 months from treatment initiation for MM. In multivariate analysis, progression-free (PFS) and overall survival were similar irrespective of induction regimen. However high risk cytogenetics and non-receipt of post-transplant maintenance/consolidation therapy were associated with higher risk of relapse. Patients receiving post-transplant therapy had significantly improved 3-year PFS vs. no post-transplant therapy (55% vs. 39%, p=0.0001). This benefit was most evident in patients not achieving at least CR post-AHCT (p=0.005). In patients receiving upfront AHCT, the choice of induction regimen (doublet or triplet therapies) appears to be of lower impact than use of post-transplant therapy.
Whether hyperosmotic blood-brain barrier (BBB) disruption is a technique that can be used to increase permeability of brain-tumor capillaries and thereby transiently increase drug delivery to the ...brain tumor is controversial. Nine virally induced brain tumors were studied in seven dogs, before and after hyperosmotic BBB disruption with 1.4 osmolar mannitol. Each dog was studied with computerized tomography (CT) after administration of the water-soluble tracer meglumine iothalamate. Each study lasted 30 minutes. A baseline CT scan and 35 to 40 additional CT scans were obtained to provide a time-related measurement of the amount of meglumine iothalamate in tissue (Am(t, and 30 plasma samples were collected to provide the time-related measurement of meglumine iothalamate in plasma (Cp(t. The data were analyzed by three different methods: 1) a two-compartment model and nonlinear curve fitting were used to calculate K1 (blood-to-tissue or influx constant), k2 (tissue-to-blood or efflux constant), and Vp (plasma vascular space); 2) K1 values were calculated with a two-compartment model, assuming no efflux, at the time point for each CT scan; and 3) a "tissue advantage ratio" was calculated that expressed the ratio of tissue uptake of meglumine iothalamate at each time point, comparing values before and after BBB disruption. Regardless of which method of data analysis was used, there was a marked and significant increase in transcapillary transport of meglumine iothalamate to tumor-free brain regions, while there was only a small, transient, and insignificant increase to the brain tumors. Although there were often marked increases in delivery to cortex in the same hemisphere as the tumors, there was no significant increase to brain immediately surrounding the tumors, perhaps due to altered circulatory dynamics in this region. These data raise serious questions as to the wisdom of using this technique to increase drug delivery to brain tumors in patients and strongly support the continued study of this technique in experimental brain tumors before it is used in patients.
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