Multiple Myeloma

Final results of PX-171-003-A0, part 1 of an open-label, single-arm, phase II study of carfilzomib in patients with relapsed and refractory multiple myeloma

Genzyme has won a nod from the FDA to market Mozobil (plerixafor) in the U.S. The drug is intended to be used in combination with granulocyte-colony stimulating factor to mobilize hematopoietic stem cells to the bloodstream for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma and multiple myeloma. The product has also been granted orphan drug designation by the FDA.

Australian researchers reported that multiple myeloma patients who expressed cyclin DI were more likely to achieve a response to treatment with bortezomib (Velcade). Mark A. Dawson, MD, Andrew Spenser, MD, and colleagues aimed to identify the patients who would fare best with bortezomib salvage therapy.

The National Institute for Health and Clinical Excellence rejected lenalidomide (Revlimid) in combination with dexamethasone for treating multiple myeloma patients who have already received at least one prior therapy.

FDA has approved Millennium and Takeda’s Velcade (bortezomib) for previously untreated multiple myeloma.

Patients with multiple myeloma are more likely to mobilize sufficient numbers of hematopoietic stem cells (HSCs) when plerixafor (AMD3100) is given with G-CSF (Neupogen) than with G-CSF alone.

As a young boy, Vincent DeVita dissected frogs on the front steps of his parents' house in Yonkers. In the eyes of his encouraging mother, he was already a budding physician fascinated by the internal complications of life.

While reduced-intensity conditioning allows hematopoietic stem cell transplant (HSCT) in older cancer patients who cannot tolerate standard conditioning regimens, only about one-third of such patients have an HLA-matched related donor available. For these patients, stem cells derived from unrelated umbilical cord blood (UCB) may provide a suitable and convenient alternative

;In patients with newly diagnosed multiple myeloma, the addition of bortezomib (Velcade) to thalidomide (Thalomid) and dexamethasone significantly increased response rates, compared with thalidomide plus dexamethasone alone, when used as induction therapy prior to autologous stem cell transplant (ASCT

In newly diagnosed multiple myeloma patients, lenalidomide (Revlimid) plus low-dose dexamethasone led to superior overall survival, compared with the standard regimen of lenalidomide plus high-dose dexamethasone

Use of intensive immunochemotherapy plus purged stem-cell support can result in long-term survival in patients with mantle cell lymphoma, suggesting that MCL could be considered as curable. Christian Geisler, MD, PhD, of Rigshospitalet, Copenhagen, Denmark, presented this provocative idea, based on final results of the MCL2 study, at ASH 2007 (abstract LB1), speaking on behalf of the Nordic Lymphoma Group.

Kosan Biosciences Incorporated has announced that the Tanespimycin in Myeloma Evaluation (TIME-1) pivotal phase III trial for its Hsp90 inhibitor tanespimycin as a potential treatment for multiple myeloma is open for enrollment

Sunesis and MMRC collaborate to study SNS-032 in myeloma

FDA has granted approval for use of Millennium Pharmaceuticals' Velcade (bortezomib) in myeloma patients with impaired kidney function without dose adjustments. The expanded label approval includes patients requiring dialysis.

Interim results of the large international phase III VISTA trial in patients with newly diagnosed multiple myeloma showed a significant improvement in all efficacy measures for bortezomib (Velcade), melphalan, and prednisone vs melphalan/prednisone.

Millennium Pharmaceuticals, Inc, announced that the interim analysis results of the large, international phase III VISTA trial in patients with newly diagnosed multiple myeloma showed that VMP therapy (bortezomib [Velcade], melphalan [Alkeran], and prednisone) demonstrated a highly statistically significant improvement in all efficacy measures, including time-to-disease progression, complete remission rate, progression-free survival, and overall survival, compared to MP (melphalan and prednisone) alone.

Millennium Pharmaceuticals, Inc. has initiated a randomized, multicenter phase II trial to evaluate the efficacy of combining bortezomib (Velcade), lenalidomide (Revlimid) and dexamethasone with or without cyclophosphamide as front-line therapy of multiple myeloma. The trial, named EVOLUTION, is led by Vincent Rajkumar, MD, professor of medicine at the Mayo Clinic.

The Multiple Myeloma Research Consortium (MMRC) and Proteolix, Inc. (South San Francisco, California) have begun enrolling patients in a multicenter phase II clinical trial of Proteolix's proteasome inhibitor carfilzomib (PR-171) in patients with relapsed and refractory multiple myeloma.

Millennium Pharmaceuticals, Inc. has initiated a randomized, multicenter, company-sponsored phase III trial to determine the most effective Velcade (bortezomib)-based combination therapy with approved agents for the treatment of newly diagnosed multiple myeloma patients who are ineligible for stem cell transplantation

lenalidomide (Revlimid) with reduced doses of the steroid dexamethasone in the treatment of multiple myeloma.

Efficacy was high and mortality was low with Total Therapy 3 (TT3), the latest version of Total Therapy for myeloma

The US Food and Drug Administration (FDA) has approved the use of Doxil (doxorubicin liposome injection, Ortho Biotech) in combination with Velcade for Injection (bortezomib, Millennium) to treat patients with multiple myeloma who have not previously received Velcade and have received at least one prior therapy.

NORWALK, Connecticut—The Multiple Myeloma Research Consortium (MMRC) and Nereus Pharmaceuticals, Inc., San Diego, have initiated enrollment in a multicenter phase I clinical trial to study Nereus' novel, second-generation proteasome inhibitor NPI-0052 in patients with relapsed or relapsed/refractory multiple myeloma. Participants in the open-label study will receive escalating, once-weekly intravenous doses of NPI-0052. The compound was discovered during the fermentation of a new marine actinomycete (Salinispora tropica).

The American Society of Clinical Oncology (ASCO) has developed updated guideline recommendations on the use of bisphosphonates in patients with multiple myeloma. The key recommendations address three areas: therapy duration, dosage, and monitoring; osteonecrosis of the jaw; and several previous recommendations.

Our better understanding of the complex interaction of multiple myeloma (MM) cells with their bone marrow microenvironment and the signaling pathways that are dysregulated in this process has resulted in a dramatic increase in the therapeutic agents available for this disease. A number of these new agents have demonstrated significant activity in patients with MM. Over the past 5 years, three drugs have received approval from the US Food and Drug Administration for therapy in MM—bortezomib, thalidomide, and lenalidomide. To date, the choice of therapy for MM is not individualized according to the biologic characteristics of the disease, but future studies should enable us to identify patients who may benefit most from certain therapeutic interventions, and thus develop individualized therapy for MM. In this review, we will present some of the treatment algorithms currently developed for patients with MM and focus on established advances in therapy, specifically with thalidomide, bortezomib, and lenalidomide. We will also discuss some of the emerging novel therapeutic agents showing promise in phase I/II clinical trials in MM.