Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma.

It is important to have an effective therapy for patients with multiple myeloma (MM) at first relapse, particularly if an autologous stem cell transplant (ASCT) is considered at this stage. This multicenter, phase 2 trial evaluated the efficacy and safety of weekly oral pomalidomide-cyclophosphamide-dexamethasone (PCD) in patients with MM in first relapse after treatment with lenalidomide-bortezomib-dexamethasone (RVD). All patients had received RVD as induction and consolidation therapy, plus lenalidomide maintenance for 1 year (arm A).

Salvage therapy post pomalidomide-based regimen in relapsed/refractory myeloma.

The combination of pomalidomide and low-dose dexamethasone (Pom-Dex) has proved effective and safe in patients with end-stage relapsed/refractory multiple myeloma (RRMM), otherwise characterized by a very poor outcome. MM remains an incurable disease with unavoidable relapses, and the outcome after pomalidomide is still dismal. However, some patients demonstrate prolonged survival even beyond pomalidomide therapy.

Bortezomib, Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Cell Leukemia: A Prospective Phase II Study of the Intergroupe Francophone du Myélome.

Purpose: Primary plasma cell leukemia (pPCL) is a rare and aggressive malignancy with a poor prognosis. With conventional chemotherapy, patients typically die within 1 year. In all but one of the retrospective studies reported to date, bortezomib and lenalidomide seem to improve survival.

Pomalidomide plus low-dose dexamethasone in multiple myeloma with deletion 17p and/or translocation (4;14): IFM 2010-02 trial results.

The combination of pomalidomide and low-dose dexamethasone (Pom-Dex) can be safely administered to patients with end-stage relapsed/refractory multiple myeloma (RRMM). However, we observed a shorter median progression-free survival (PFS) and overall survival (OS) in these patients when characterized with adverse cytogenetics (deletion 17p and translocation [4;14]) in the Intergroupe Francophone Myélome (IFM) 2009-02 trial. We then sought to determine whether MM with adverse cytogenetics would benefit more from Pom-Dex if exposed earlier in the multicenter IFM 2010-02 trial.

The translocation t(4;14) can be present only in minor subclones in multiple myeloma.

Purpose: Although the translocation t(4;14) is supposed to be a primary event in multiple myeloma, we have been surprised to observe that in large relapse series of patients, the t(4;14) can be observed only in subpopulations of plasma cells, in contrast to what is seen at diagnosis. This observation raised the question of possible subclones harboring the translocation that would be observable only at the time of relapse.

Experimental Design: To address this issue, we analyzed by FISH a cohort of 306 patients for whom we had at least two samples obtained at different disease phases.

Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the intergroupe francophone du myélome experience.

Purpose: Chromosomal abnormalities, especially t(4;14) and del(17p), are major prognostic factors in patients with multiple myeloma (MM). However, this has been especially demonstrated in patients age < 66 years treated with intensive approaches. The goal of this study was to address this issue in elderly patients treated with conventional-dose chemotherapy.

Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials.

Treatment with melphalan-prednisone-thalidomide improves the outcome of patients with multiple myeloma and is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. A meta-analysis of data from individual patients (n=1680) in six randomized trials was performed, comparing the effects of melphalan-prednisone-thalidomide versus melphalan-prednisone.

Long-term analysis of the IFM 99 trials for myeloma: cytogenetic abnormalities [t(4;14), del(17p), 1q gains] play a major role in defining long-term survival.

Purpose: In multiple myeloma, many prognostic parameters have been proposed. However, all of these predict shorter survival. To identify patients with a longer life expectancy, we updated the data of patients treated in the IFM (Intergroupe Francophone du Myelome) 99-02 and 99-04 trials.

Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma.

The Intergroupe Francophone du Myelome conducted a randomized trial to compare bortezomib-dexamethasone (VD) as induction before high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to a combination consisting of reduced doses of bortezomib and thalidomide plus dexamethasone (vtD) in patients with multiple myeloma. Overall, a total of 199 patients were centrally randomly assigned to receive VD or vtD. After 4 cycles, the complete response (CR) rate was the same in both groups (13% in the vtD arm, 12% in the VD arm, P = .

Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p).

Purpose: Cytogenetics is an important prognostic parameter in multiple myeloma (MM). Patients presenting with either t(4;14) or del(17p) are known to have a short event-free survival (EFS) and overall survival (OS). Some preliminary data suggest that bortezomib is able to overcome these prognostic parameters.

Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy.

Dexamethasone alone increases life expectancy in patients with relapsed multiple myeloma (MM); however, no large randomized study has compared dexamethasone and dexamethasone-based regimens with standard melphalan-prednisone in newly diagnosed MM patients ineligible for high-dose therapy. In the Intergroupe Francophone du Myélome (IFM) 95-01 trial, 488 patients aged 65 to 75 years were randomized between 4 regimens of treatment: melphalan-prednisone, dexamethasone alone, melphalan-dexamethasone, and dexamethasone-interferon alpha. Response rates at 6 months (except for complete response) were significantly higher among patients receiving melphalan-dexamethasone, and progression-free survival was significantly better among patients receiving melphalan (P < .

Karyotypic abnormalities in myelofibrosis following polycythemia vera.

Polycythemia vera (PV) is a chronic myeloproliferative disease characterized by an increase of total red cell volume; in 10% to 15% of cases, bone marrow fibrosis complicates the course of the disease after several years, resulting in a hematologic picture mimicking myelofibrosis with myelocytic metaplasia (MMM). This condition is known as post polycythemic myelofibrosis (PPMF). Among 30 patients with PPMF followed in Northern France, 27 (90%) expressed one or two abnormal clones in myelocytic cell cultures.

Effects of long-term intravenous ibandronate therapy on skeletal-related events, survival, and bone resorption markers in patients with advanced multiple myeloma.

Purpose: Bisphosphonates have been found to reduce the incidence of skeletal-related events (SREs) in patients with multiple myeloma. This is the first double-blind, randomized, placebo-controlled study to assess the efficacy of ibandronate, a third-generation amino-bisphosphonate, in preventing SREs in advanced-stage multiple myeloma patients.

Patients And Methods: Patients with multiple myeloma stage II or III were randomly assigned to receive either ibandronate 2 mg or placebo as a monthly intravenous (IV) bolus injection for 12 to 24 months in addition to conventional chemotherapy.

Alpha-interferon in combination with cytarabine in children with Philadelphia chromosome-positive chronic myeloid leukemia.

Background: Philadelphia chromosome-positive chronic myelogenous leukemia (CML) is a rare disease in children, and the optimal therapy is not clearly defined in these patients when a human leukocyte antigen-identical donor is not available. The present work focuses on the therapeutic efficacy and the toxicity of interferon (IFN) alpha 2b in combination with cytosine arabinosine (Ara-C) in patients younger than age 18 years enrolled in the randomized trial CML 91, which compared the efficacy of IFN and cytosine arabinoside (Ara-C) with IFN alone in 810 patients with CML in the chronic phase.

Patients And Methods: Twelve patients younger than age 18 years were enrolled in the randomized trial CML 91.