DNA methylation inhibition in myeloma: Experience from a phase 1b study of low-dose continuous azacitidine in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma.

The DNA methyltransferase inhibitor azacytidine (aza) may reactivate pathways associated with plasma cell differentiation, cell cycle control, apoptosis, and immune recognition and thereby restore sensitivity to lenalidomide (len) and dexamethasone (dex) in relapsed and/or refractory multiple myeloma (RRMM). We aimed to develop an aza regimen that reaches epigenetically active levels 8 times in 28 days with less bone marrow toxicity than the myeloid malignancy standard of 7 consecutive doses to enable safe combination with len. Aza was escalated from 30 mg/m once a week up to a predefined maximum of 50 mg/m twice a week in combination with GFR-adjusted len (≥ 60 mL/min: 25 mg, 3059 mL/min: 10 mg) day 1 to 21 every 28 days and dex 40 mg once a week followed by a limited expansion study to a total N of 23 at the highest tolerated dose.

Combination of rituximab and oral melphalan and prednisone in newly diagnosed multiple myeloma.

Clonotypic B lymphocytes may underlie relapse of patients with multiple myeloma. Rituximab, a CD20 monoclonal antibody, may result in eradication of the monoclonal B cells. We conducted a phase II study of rituximab in combination with melphalan and prednisone therapy (MP) followed by rituximab maintenance in newly diagnosed multiple myeloma patients.

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.

The role of race, socioeconomic status, and distance traveled on the outcome of African-American patients with multiple myeloma.

The incidence and mortality of multiple myeloma (MM) in African-Americans is double that in whites. We questioned whether race, socioeconomic status, and distance traveled affect overall survival. In a retrospective review of the records of 292 patients with MM.

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.

Efficacy and safety results with the combination therapy of arsenic trioxide, dexamethasone, and ascorbic acid in multiple myeloma patients: a phase 2 trial.

Background: Single-agent arsenic trioxide has shown promising results in patients with relapsed or refractory multiple myeloma (MM). Because preclinical data suggested greater activity with dexamethasone and ascorbic acid, a phase 2 trial of the combination of arsenic trioxide, dexamethasone, and ascorbic acid in patients with relapsed or refractory MM was conducted.

Methods: Twenty patients in whom no more than two previous therapies had failed were enrolled.

The role of aspirin in the prevention of thrombotic complications of thalidomide and anthracycline-based chemotherapy for multiple myeloma.

Objective: To study the efficacy of daily low-dose aspirin (81 mg orally) in decreasing the incidence of venous thromboembolic events (VTEs) in patients with multiple myeloma receiving pegylated doxorubicin, vincristine, and decreased-frequency dexamethasone, plus thalidomide (DVd-T).

Patients And Methods: In this phase 2 clinical trial of DVd-T, conducted by the Cleveland Clinic Foundation from August 2001 to October 2003, 105 patients were enrolled. The first 35 patients experienced increased numbers of VTEs.

Use of melphalan, thalidomide, and dexamethasone in treatment of refractory and relapsed multiple myeloma.

Twenty-one patients with relapsed and refractory Durie-Salmon stage III multiple myeloma who had either failed at least three previous regimens or presented with poor performance status, neutropenia, or thrombocytopenia were treated with up to four cycles of combination melphalan (50 mg intravenously), thalidomide (titrated to target of 400 mg orally daily), and dexamethasone (40 mg/day orally on d 1 to 4) every 4-6 wk. Maintenance treatment consisting of daily thalidomide and monthly dexamethasone was continued until disease progression. Although generally tolerated, combination melphalan/thalidomide/dexamethasone produced grade 4 neutropenia and thrombocytopenia in 52% and 38% of patients, respectively.