The investigational agent MLN2238 induces apoptosis and is cytotoxic to CLL cells in vitro, as a single agent and in combination with other drugs.

Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in the U.S. The course of the disease has been shown to be negatively impacted by increased levels of BCL2.

AT-101 downregulates BCL2 and MCL1 and potentiates the cytotoxic effects of lenalidomide and dexamethasone in preclinical models of multiple myeloma and Waldenström macroglobulinaemia.

Multiple myeloma, the second most common haematological malignancy in the U.S., is currently incurable.

Neem leaf extract induces cell death by apoptosis and autophagy in B-chronic lymphocytic leukemia cells.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is currently incurable. To expand the therapeutic armamentarium, we investigated neem leaf extract (NLE) after a patient with CLL demonstrated disease regression upon taking oral NLE. NLE-mediated apoptosis was examined in peripheral blood mononuclear cells (PBMCs) from 41 patients with CLL.

Development and characterization of a novel human Waldenström macroglobulinemia cell line: RPCI-WM1, Roswell Park Cancer Institute - Waldenström Macroglobulinemia 1.

Understanding the biology of Waldenström macroglobulinemia is hindered by a lack of preclinical models. We report a novel cell line, RPCI-WM1, from a patient treated for WM. The cell line secretes human immunoglobulin M (h-IgM) with κ-light chain restriction identical to the primary tumor.

Monoallelic and biallelic deletions of 13q14.3 in chronic lymphocytic leukemia: FISH vs miRNA RT-qPCR detection.

Deletion of 13q14.3 (del(13q)) is the most common cytogenetic abnormality in chronic lymphocytic leukemia (CLL) and implies a favorable prognosis. We explored the feasibility of detecting del(13q) by real-time quantitative polymerase chain reaction (PCR) for miR-15a and miR-16-1, whose loci are located in the deleted region.

Acyclovir prophylaxis against varicella zoster virus reactivation in multiple myeloma patients treated with bortezomib-based therapies: a retrospective analysis of 100 patients.

Background: Previous studies have indicated that, in patients with multiple myeloma (MM), bortezomib is associated with an increased incidence of herpes zoster, resulting from reactivation of latent varicella zoster virus (VZV).

Objective: Our objective was to determine whether increased risk of VZV reactivation could be abrogated by using prophylactic acyclovir.

Methods: We retrospectively evaluated 100 consecutive MM patients treated with bortezomib-based therapies at the Roswell Park Cancer Institute for development of herpes zoster.

Downregulation of BCL2 by AT-101 enhances the antileukaemic effect of lenalidomide both by an immune dependant and independent manner.

Over-expression of anti-apoptotic BCL2 has been reported in chronic lymphocytic leukaemia (CLL), but targeting BCL2 alone did not yield appreciable clinical results. However, it was demonstrated that BCL2 inhibitors enhanced the clinical efficacy of chemo and immunotherapeutics. Lenalidomide, an immunomodulator, is clinically effective in CLL and can enhance the anti-CLL effects of CD20 targeting monoclonal antibody, rituximab.

Targeted treatment for chronic lymphocytic leukemia.

The treatment of chronic lymphocytic leukemia (CLL) has evolved over the last few decades. Recognition has increased of several key components of CLL biology currently manipulated for therapeutics. A milestone in the treatment of CLL was reached with the incorporation of immunotherapy with conventional chemotherapy.

Maintaining bone health in patients with multiple myeloma: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

About 90% of individuals with multiple myeloma will develop osteolytic bone lesions from increased osteoclastic and decreased osteoblastic activity. Severe morbidities from pathologic fractures and other skeletal events can lead to poor circulation, blood clots, muscle wasting, compromised performance status, and overall poor survival. Supportive care targeting bone disease is an essential adjunct to antimyeloma therapy.

A steroid-independent regimen of bortezomib, liposomal doxorubicin and thalidomide demonstrate high response rates in newly diagnosed multiple myeloma patients.

Novel agents have provided a new foundation for multiple myeloma therapies. When combined with other anti-myeloma agents, these compounds significantly enhance clinical efficacy. High-dose steroids are frequently used in anti-myeloma combination regimens; however, the doses employed are often poorly tolerated, especially in patients with concurrent comorbid conditions.

Tumor flare reaction associated with lenalidomide treatment in patients with chronic lymphocytic leukemia predicts clinical response.

Background: In patients with chronic lymphocytic leukemia (CLL), treatment with lenalidomide induces a unique, previously uncharacterized, immune response called tumor flare reaction (TFR). The clinical significance of this reaction remains unknown.

Methods: Forty-five patients with CLL who were treated with lenalidomide in a phase 2 clinical trial were evaluated for the clinical features, intensity, and duration of TFR.

Plasma cell leukaemia and other aggressive plasma cell malignancies.

Extramedullary plasma cell cancers, such as plasma cell leukaemia (PCL) and multiple extramedullary plasmacytomas (MEP) are very aggressive malignancies. These can be primary (de-novo) or secondary due to progressive prior multiple myeloma (MM). Recent reports suggest an increase in incidence of these disorders.

Management of patients with chronic lymphocytic leukemia treated with lenalidomide.

Lenalidomide is an immunomodulatory drug that has shown preliminary activity in the treatment of chronic lymphocytic leukemia (CLL). Much is known about the safety profile of lenalidomide from experience in other hematologic malignancies, such as myelodysplastic syndromes and multiple myeloma. In addition to the known adverse effects associated with lenalidomide (e.

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.

Efficacy of lenalidomide in patients with chronic lymphocytic leukemia with high-risk cytogenetics.

Patients with chronic lymphocytic lymphoma (CLL) with high-risk cytogenetics [del(11q)(q22.3) or del(17p)(p13.1)] have limited therapeutic options and their prognosis remains poor.

Extent of disease burden determined with magnetic resonance imaging of the bone marrow is predictive of survival outcome in patients with multiple myeloma.

Background: Multiple myeloma (MM) remains an incurable cancer. Treatment often is initiated at the time patients experience a progressive increase in tumor burden. The authors of this report investigated magnetic resonance imaging of the bone marrow (BM-MRI) as a novel approach to quantify disease burden and validated a staging system by correlating BM-MRI with common clinical and laboratory parameters.

Remission induction with lenalidomide alone in a patient with previously untreated plasmablastic myeloma: a case report.

Multiple myeloma patients with plasmablastic morphology of tumor cells and extramedullary presentation of disease often have an aggressive clinical course and resistance to chemotherapy. We describe a case of an elderly patient who presented with extramedullary, IgA-lambda-secreting multiple myeloma with plasmablastic features who demonstrated impressive clinical response to single-agent lenalidomide. This is the first description of a plasmablastic variety of multiple myeloma successfully treated with lenalidomide alone.

Bortezomib in combination with pegylated liposomal doxorubicin and thalidomide is an effective steroid independent salvage regimen for patients with relapsed or refractory multiple myeloma: results of a phase II clinical trial.

Novel agents have demonstrated enhanced efficacy when combined with other antimyeloma agents especially dexamethasone. The steroid doses employed in myeloma regimens are often poorly tolerated. Therefore, in a phase II clinical trial we investigated the efficacy of a steroid-free combination including bortezomib, pegylated liposomal doxorubicin and thalidomide (VDT regimen).

Thromboembolic events associated with novel therapies in patients with multiple myeloma: consensus statement of the IMF Nurse Leadership Board.

Patients with myeloma are at risk for serious and life-threatening thromboembolic events because of their disease, individual risk factors, and antimyeloma or other medications. The International Myeloma Foundation's Nurse Leadership Board developed this consensus statement for assessment and prevention of thromboembolic events. Prophylactic measures are categorized as mechanical, regimen related, and antithrombotic drug, based on individual and myeloma-related risk factors.

Management of side effects of novel therapies for multiple myeloma: consensus statements developed by the International Myeloma Foundation's Nurse Leadership Board.

Nurses play an essential role in managing the care of patients with multiple myeloma, who require education and support to receive and adhere to optimal therapy. The International Myeloma Foundation created a Nurse Leadership Board comprised of oncology nurses from leading cancer centers and community practices. An assessment survey identified the need for specific recommendations for managing key side effects of novel antimyeloma agents.

Clinical impact of bortezomib in frontline regimens for patients with multiple myeloma.

Standard frontline therapy for multiple myeloma comprises cytoreductive therapy with or without consolidative high-dose therapy plus stem cell transplantation (HDT-SCT). Despite therapeutic advances, the disease remains incurable; most patients relapse following frontline treatment and die within 5 years of diagnosis. New options are required to enhance and prolong response, and improve survival, particularly for elderly patients and those with renal dysfunction.

Bortezomib in combination with pegylated liposomal doxorubicin for the treatment of multiple myeloma.

Many novel agents and new combinations (including bortezomib, thalidomide, and lenalidomide) have been developed in recent years for the treatment of multiple myeloma (MM), creating major shifts in therapeutic management. Achieving complete response (CR)/near CR (nCR) generally serves as a reliable clinical surrogate for overall treatment outcome, ie, prolonged survival. Indeed, some newer induction regimens are yielding similar median time to disease progression effects compared with transplantation.

Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study.

Patients with multiple myeloma (MM) frequently present with concomitant renal dysfunction, and those requiring dialysis have particularly poor outcomes. Bortezomib is a reversible proteasome inhibitor with significant activity in MM. This retrospective case analysis evaluated the feasibility and activity of bortezomib-based therapy in MM patients (n = 24) requiring dialysis support for advanced renal failure.