Disease and outcome disparities in multiple myeloma: exploring the role of race/ethnicity in the Cooperative Group clinical trials.

Multiple myeloma (MM) is an incurable hematologic malignancy with disparities in outcomes noted among racial-ethnic subgroups, likely due to disparities in access to effective treatment modalities. Clinical trials can provide access to evidence-based medicine but representation of minorities on therapeutic clinical trials has been dismal. We evaluated the impact of patient race-ethnicity in pooled data from nine large national cooperative group clinical trials in newly diagnosed MM.

The Role of Minimal Residual Disease Testing in Myeloma Treatment Selection and Drug Development: Current Value and Future Applications.

Treatment of myeloma has benefited from the introduction of more effective and better tolerated agents, improvements in supportive care, better understanding of disease biology, revision of diagnostic criteria, and new sensitive and specific tools for disease prognostication and management. Assessment of minimal residual disease (MRD) in response to therapy is one of these tools, as longer progression-free survival (PFS) is seen consistently among patients who have achieved MRD negativity. Current therapies lead to unprecedented frequency and depth of response, and next-generation flow and sequencing methods to measure MRD in bone marrow are in use and being developed with sensitivities in the range of 10 to 10 cells.

Norwegian scabies - rare case of atypical manifestation.

Human scabies affects all social classes and different races around the world. It is highly contagious, but the exact figures on its prevalence are unknown. A 19-year-old male patient was admitted to the emergency room reporting fever (38°C) and multiple lesions throughout the body, except face, soles, and palms.

Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide: a long-term follow-up study of the US intergroup phase III trial E2997.

Fludarabine (F) and cyclophosphamide (C) remain backbones of up-front chemotherapy regimens for chronic lymphocytic leukemia (CLL). We report long-term follow-up of a randomized F vs. FC trial in untreated CLL (#) .

A phase II trial of BAY 43-9006 (sorafenib) (NSC-724772) in patients with relapsing and resistant multiple myeloma: SWOG S0434.

The authors assessed the overall response rate, including confirmed complete response (CR) and partial response, in patients with relapsed/refractory multiple myeloma treated with sorafenib. Qualitative and quantitative toxicities associated with this regimen were evaluated. Patients were eligible if they had a confirmed diagnosis of refractory or relapsed (RR) multiple myeloma (MM) with measurable monoclonal protein.

Mature results of MM-011: a phase I/II trial of liposomal doxorubicin, vincristine, dexamethasone, and lenalidomide combination therapy followed by lenalidomide maintenance for relapsed/refractory multiple myeloma.

A previous interim report of MM-011, the first study that combined lenalidomide with anthracycline-based chemotherapy followed by lenalidomide maintenance for relapsed and/or refractory multiple myeloma (RRMM), showed promising safety and activity. We report the long-term outcomes of all 76 treated patients with follow-up ≥ 5 years. This single-center phase I/II study administered lenalidomide (10 mg on days 1-21 of every 28-day cycle), intravenous liposomal doxorubicin (40 mg/m(2) on day 1), dexamethasone (40 mg on days 1-4), and intravenous vincristine (2 mg on day 1).

Phase II study of pegylated liposomal doxorubicin, low-dose dexamethasone, and lenalidomide in patients with newly diagnosed multiple myeloma.

Our previous phase I/II trial of pegylated liposomal doxorubicin (PLD), low-dose dexamethasone, and lenalidomide in patients with relapsed and refractory myeloma showed an overall response rate of 75%, with 29% achieving ≥ VGPR. Here, we investigated this combination (PLD 30 or 40 mg/m(2) intravenously, day 1; dexamethasone 40 mg orally, days 1-4; lenalidomide 25 mg orally, days 1-21; administered every 28 days) in a phase II study in patients with newly diagnosed symptomatic multiple myeloma to determine its efficacy and tolerability (ClinicalTrials.gov NCT00617591).

Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine: long-term follow-up of US Intergroup Study E2997.

Chemotherapy-related myeloid neoplasia (t-MN) is a significant late toxicity concern after cancer therapy. In the randomized intergroup phase 3 E2997 trial, initial therapy of chronic lymphocytic leukemia with fludarabine plus cyclophosphamide (FC) compared with fludarabine alone yielded higher complete and overall response rates and longer progression-free, but not overall, survival. Here, we report t-MN incidence in 278 patients enrolled in E2997 with a median 6.

Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232).

The Southwest Oncology Group conducted a randomized trial comparing lenalidomide (LEN) plus dexamethasone (DEX; n = 97) to placebo (PLC) plus DEX (n = 95) in newly diagnosed myeloma. Three 35-day induction cycles applied DEX 40 mg/day on days 1 to 4, 9 to 12, and 17 to 20 together with LEN 25 mg/day for 28 days or PLC. Monthly maintenance used DEX 40 mg/day on days 1 to 4 and 15 to 18 along with LEN 25 mg/day for 21 days or PLC.

Single agent lenalidomide in newly diagnosed multiple myeloma: a retrospective analysis.

Recently, lenalidomide and low dose dexamethasone were found to result in superior overall survival compared to lenalidomide and high dose dexamethasone. The immune suppressive effects of dexamethasone can antagonize lenalidomide immunomodulatory activity and may explain this observation. We conducted a retrospective analysis to evaluate the single agent activity of lenalidomide in newly diagnosed myeloma.

Prediction of response and progression in multiple myeloma with serum free light chains assay: corroboration of the serum free light chain response definitions.

Background: The International Myeloma Working Group (IMWG) proposed response and progression criteria using serum free light chain (sFLC) testing for patients with nonsecretory multiple myeloma (MM). We attempt to validate these criteria by comparing paraprotein responses with sFLC responses in patients with secretory myeloma.

Patients And Methods: Prospectively entered data for 89 patients with MM enrolled on various clinical trials at the Cleveland Clinic between April 2004 and December 2006 were reviewed.

Phase II study of thalidomide plus dexamethasone induction followed by tandem melphalan-based autotransplantation and thalidomide-plus-prednisone maintenance for untreated multiple myeloma: a southwest oncology group trial (S0204).

PURPOSE Thalidomide-dexamethasone (THAL-DEX) is standard induction therapy for multiple myeloma (MM). Tandem melphalan-based transplantations have yielded superior results to single transplantations. Phase II trial S0204 was designed to improve survival results reported for the predecessor, phase III trial S9321 by 50%.

An association between renal cell carcinoma and multiple myeloma: a case series and clinical implications.

Objective: To describe an association between renal cell carcinoma (RCC) and multiple myeloma (MM) in patients with both disorders, and suggest possible explanations for the association.

Patients And Methods: We retrospectively reviewed the records of patients with MM and RCC at the Cleveland Clinic between 1990 and 2005, and identified 1100 with MM, 2704 with RCC and eight with concomitant MM and RCC. The medical records of these eight patients were reviewed.

G1P3, an IFN-induced survival factor, antagonizes TRAIL-induced apoptosis in human myeloma cells.

The effectiveness of IFN-alpha2b for human multiple myeloma has been variable. TRAIL has been proposed to mediate IFN-alpha2b apoptosis in myeloma. In this study we assessed the effects of IFN-alpha2b signaling on the apoptotic activity of TRAIL and human myeloma cell survival.

Preclinical rationale, mechanisms of action, and clinical activity of anthracyclines in myeloma.

Multiple myeloma is an incurable disease for which there are 2 clinical research strategies. One strategy is to focus on managing the disease as a chronic process aiming to minimize the negative impact on survival with minimal or no compromise of the quality of life. The other strategy is to pursue total eradication of the malignant clone, thus achieving cure for the disease.

Multiple myeloma: most common end-organ damage and management.

End-organ damage is the factor that differentiates plasma cell dyscrasia requiring therapy (active multiple myeloma [MM]) from disease that does not require therapy (monoclonal gammopathy of undetermined significance and smoldering [asymptomatic] MM). Progressive skeletal destruction is the hallmark of MM and responsible for principle morbidity in the disease. The spine is the most afflicted skeletal organ, and vertebral fractures have significantly contributed to its poor prognosis.

CD28-mediated regulation of multiple myeloma cell proliferation and survival.

Although interactions with bone marrow stromal cells are essential for multiple myeloma (MM) cell survival, the specific molecular and cellular elements involved are largely unknown, due in large part to the complexity of the bone marrow microenvironment itself. The T-cell costimulatory receptor CD28 is also expressed on normal and malignant plasma cells, and CD28 expression in MM correlates significantly with poor prognosis and disease progression. In contrast to T cells, activation and function of CD28 in myeloma cells is largely undefined.

Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997.

Purpose: The combination of fludarabine and cyclophosphamide is an effective regimen for patients with chronic lymphocytic leukemia (CLL). However, it may be accompanied by increased toxicity compared with fludarabine alone. E2997 is a phase III randomized Intergroup trial comparing fludarabine and cyclophosphamide (FC arm) versus fludarabine (F arm) alone in patients receiving their first chemotherapy regimen for CLL.

Proteasome inhibitors in the clinical setting: benefits and strategies to overcome multiple myeloma resistance to proteasome inhibitors.

The majority of intracellular proteins undergo degradation through the ubiquitin-proteasome pathway. The proteasome pathway has a role in regulating cell proliferation, differentiation, survival and apoptosis. The naturally occurring proteasome inhibitor lactacystin was the first proteasome inhibitor noted to induce apoptosis in vitro.

Phase 2 study of pegylated liposomal doxorubicin, vincristine, decreased-frequency dexamethasone, and thalidomide in newly diagnosed and relapsed-refractory multiple myeloma.

Objective: To evaluate the efficacy and safety of adding thalidomide to the pegylated liposomal doxorubicin, vincristine, and decreased-frequency dexamethasone (DVd) regimen for multiple myeloma.

Patients And Methods: Patients newly diagnosed as having active multiple myeloma and those with relapsed-refractory disease were studied between August 2001 and October 2003. Patients received DVd as previously described.

The emerging role of arsenic trioxide as an immunomodulatory agent in the management of multiple myeloma.

Multiple myeloma is a clonal disorder of plasma cells which is considered incurable with currently available therapies. Substantial advances have been achieved in the past decade with the identification of cellular mechanisms that confer drug resistance. This has resulted in newer agents such as arsenic trioxide (Trisenoxt), lenalidomide (Revlimid) and bortezomib (Velcade) with promising activity in this disease.

Thromboembolism risk reduction in multiple myeloma patients treated with immunomodulatory drug combinations.

Deep vein thrombosis and its lethal complication pulmonary embolism are manifestations of venous thromboembolism (VTE), which is typically associated with cancer and recent major surgery. Certain solid tumors and hematologic malignancies impose an inherently elevated risk of VTE that is compounded by chemotherapy and other risk factors. Multiple myeloma (MM) and other plasma cell dyscrasias are thrombogenic as a consequence of their multiple hemostatic effects, including elevated interleukin-6 levels, pro-coagulant antibody formation, paraprotein interference with fibrin structure, activated protein C resistance, and endothelial damage.

Pharmacotherapy of multiple myeloma.

Multiple myeloma is a malignant process of the plasma cell. There is no cure for this disease and at present the focus is to manage the disease as a chronic process to achieve a good quality of life. Hopefully, with the advancement in the understanding of the pathophysiology of the disease, target therapy should allow for the control of multiple myeloma, its prevention, and/or the reversal of organ damage; therefore prolonging survival.