Myelodysplastic Syndromes

In this first part of our two-part review, we introduce mutation profiling as a relevant clinical tool for hematologists treating patients with myeloid malignancies.

Although there are currently no approved second-line therapies for high-risk MDS, researchers have discovered that rigosertib has the potential to benefit this population of patients.

A new study demonstrates that it is possible to vaccinate patients with MDS against a decitabine-induced antigen and that the level of induced expression is sufficient to trigger cytotoxicity in patient-derived vaccine-induced T cells.

A combination of the FLT3 kinase inhibitor quizartinib with 5-azacitidine or low-dose cytarabine is active in patients with FLT3-ITD mutated myeloid leukemias, according to a new study.

Researchers presented data at the 2017 ASH annual meeting about their new personalized MDS prediction model that uses clinical and genomic data to help better guide therapy and improve outcomes compared with other models.

Patients with myelodysplastic syndrome undergoing a reduced–intensity conditioning regimen prior to allogeneic stem-cell transplantation had similar 2-year survival outcomes as patients who underwent myeloablative conditioning.

The use of the thrombopoietin receptor agonist eltrombopag was clinically effective at raising platelet counts in patients with lower-risk myelodysplastic syndromes with severe thrombocytopenia.

This look ahead at hematologic malignancies in 2017 focuses on new agents being studied for the treatment of acute leukemias, myelodysplastic syndromes, and chronic lymphocytic leukemia.

Patients with AML or MDS with unfavorable risk cytogenetic profiles, TP53 mutations, or both had good clinical response and robust mutation clearance with decitabine.

A scoring system including several patient characteristics was found to have significant prognostic value for patients with myelodysplastic syndromes undergoing allogeneic hematopoietic cell transplantation.

Adding the HDAC inhibitor valproic acid to decitabine did not improve outcomes in patients with myelodysplastic syndromes or acute myeloid leukemia.

Myelodysplastic syndromes, also referred to collectively as MDS, have significant biological and clinical heterogeneity, a highly variable natural history, and a complex pathobiology that is not clearly understood.

The myelodysplastic syndromes (MDS) are a heterogeneous spectrum of clonal hematopoietic diseases characterized by bone marrow hypercellularity, dysplasia of cellular elements, and consequent inadequate hematopoiesis, with resultant peripheral blood cytopenias.

The review by Dr. Akhtari outlines the diagnosis, prognosis, and treatment options for patients with myelodysplastic syndromes (MDS), and touches on the current challenges in treating patients suffering from MDS.

There's reason to question whether lenalidomide is the cause of secondary cancers in patients who take it as an adjuvant. But new scrutiny may help to clarify how it acts against the primary.

For years, chemotherapy-associated myelosuppression has represented a major limitation to a patient’s tolerance of anticancer therapy. In addition, the clinical consequences of chemotherapy-induced myelosuppression (such as febrile neutropenia, dose reductions, or lengthy dose delays) may have had significant negative effects on quality of life or even response to treatment.

Our case illustrates the fact that MDS-associated GS can be treated palliatively with radiation and hypomethylating agents in an appropriate setting. With the growing geriatric patient population, effective treatment options are needed in this disease.

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

Studies presented at the 2007 San Antonio Breast Cancer Symposium raise new questions about the role of anthracycline-based regimens as adjuvant therapy in early breast cancer, suggesting that these regimens may be appropriate only for a small subset of patients.

An HLA-A2-restricted peptide vaccine given as salvage therapy to patients with acute myeloid leukemia or myelodysplastic syndrome showed evidence of immunological, molecular, and clinical efficacy

In a phase II trial of diffuse large B cell lymphoma (DLBCL) patients with high-risk or relapsed chemosensitive disease, the combination of the radioimmunotherapy (RIT) agent 131I tositumomab (Bexxar) plus BEAM chemotherapy proved safe as an outpatient preparative regimen for autologous peripheral blood stem cell transplant (PSCT)

Anastrozole (Arimidex): Conversion to regular approval for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. Issued September 2005.Bevacizumab (Avastin): Treatment of metastatic colon cancer. Issued June 2006. Bortezomib (Velcade): Treatment of previously treated mantle cell lymphoma. Issued December 2006. Capecitabine (Xeloda): Single-agent adjuvant treatment of Dukes’ stage C colon cancer in patients who have undergone complete resection of the primary tumor and for whom fluoropyrimidine therapy alone would be preferred. Issued June 2005. Cetuximab (Erbitux): For use in combination with radiation therapy for the treatment of patients with unresectable squamous cell cancer of the head and neck and for patients whose disease has metastasized despite use of standard chemotherapy. Issued March 2006. Dasatinib (Sprycel): Treatment of chronic myelogenous leukemia and Philadelphia-chromosome positive acute lymphoblastic leukemia. Issued June 2006. Decitabine (Dacogen): Treatment of myelodysplastic syndromes. Issued May 2006. Docetaxel (Taxotere): In combination with cisplatin and fluorouracil prior to radiotherapy for treatment of inoperable locally advanced squamous cell carcinoma of the head and neck. Issued October 2006. Erlotinib (Tarceva): Treatment of locally advanced or metastatic non–small-cell lung cancer following failure of at least one prior chemotherapy regimen. Issued November 2004; In combination with gemcitabine for first-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer. Approved for this indication November 2005. Exemestane (Aromasin): Adjuvant treatment of postmenopausal women with estrogen receptor positive early breast cancer who have received 2 or 3 years of tamoxifen therapy and are switched to exemestane for completion of 5 years of adjuvant hormonal therapy. Issued October 2005.Gefitinib (Iressa): AstraZeneca and FDA approved new labeling for gefitinib limiting its use to cancer patients who are currently benefiting or have previously benefited from treatment with this agent. Distribution limited under a risk-management plan called Iressa Access Program. Issued June 2005.Gemcitabine (Gemzar): In combination with carboplatin for treatment of ovarian cancer. Issued July 2006.Lapatinib (Tykerb): Treatment in combination with capecitabine of advanced or metastatic breast cancer (HER2-positive). Issued March 2007.Lenalidomide (Revlimid): Treatment of patients with deletion 5q cytogenetic abnormality subtype of myelodysplastic syndrome. Issued December 2005. Treatment of multiple myeloma. June 2006.Letrozole (Femara): Adjuvant treatment of postmenopausal women with hormone-receptor-positive early breast cancer. Issued January 2006.Nelarabine (Arranon): Accelerated approval for the treatment of refractory or relapsed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Patients must have had failure of at least two prior chemotherapy regimens. Issued October 2005.Panitumumab (Vectibix): Treatment of colorectal cancer that has metastasized following standard chemotherapy. Issued September 2006. Pegaspargase (Oncaspar): Treatment of acute lymphoblastic leukemia in adults and children. Issued July 2006. Rituximab (Rituxan): First-line treatment of diffuse large B-cell, CD20 positive, non-Hodgkin’s lymphoma in combination with CHOP or other anthracycline-based chemotherapy regimens. Issued February 2006. Sorafenib (Nexavar): Treatment of advanced renal cell carcinoma in adults. Issued December 2005.Sunitinib maleate (Sutent): Treatment of gastrointestinal stromal tumor (GIST) after disease progression or intolerance to imatinib mesylate (Gleevec). Also accelerated approval for the treatment of advanced renal cell carcinoma based on partial response rates and response duration. Issued January 2006. Approved for first-line treatment of advanced renal cell carcinoma. Issued February 2007.Thalidomide (Thalomid): Treatment of multiple myeloma. Issued May 2006.Topotecan (Hycamtin): Treatment of cervical cancer. Issued June 2006.Trastuzumab (Herceptin): Expanded use of trastuzumab post surgery in combination with other cancer drugs for treatment of HER-2 positive early breast cancer. Issued November 2006.Vorinostat (Zolinza): Treatment of cutaneous manifestations of progressive, recurrent cutaneous T-cell lymphoma. Issued October 2006.

New updated results from a pivotal phase II trial evaluating lenalidomide (Revlimid) in patients with myelodysplastic syndromes (MDS)

IV Vidaza Approved; Oral Formulation to Be Tested

Two clinical studies with a total of 1,202 patients have found posaconazole (Noxafil) significantly more effective than two other antifungal agents in preventing fatal invasive fungal infections in acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) patients who develop neutropenia as a result of chemotherapy

The US Food and Drug Administration (FDA) has approved Schering-Plough Corporation's Noxafil (posaconazole) Oral Suspension for the prevention of invasive Aspergillus and Candida infections in patients age 13 years and older at high risk of developing these infections.

The Food and Drug Administration (FDA) has approved the marketing of Dacogen (decitabine for injection, MGI Pharma) for the treatment of all forms of myelodysplastic syndrome (MDS). The agency acted after reviewing data submitted by the sponsor from a pivotal phase III trial, in which patients evaluable for response had a 21% overall response rate, and two supporting studies.

In a phase III trial, posaconazole (Noxafil Oral Suspension), an investigational broad-spectrum triazole antifungal, significantly reduced the incidence of serious invasive fungal infections (IFIs) and of aspergillosis, and demonstrated a survival benefit, compared with standard azole antifungal treatment in high-risk neutropenic patients undergoing intensive chemotherapy.

The FDA has given priority review status to Celgene Corporation's supplemental new drug application for lenalidomide (Revlimid) in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma.

Adjuvant dose-dense chemotherapy for breast cancer was validated by the updated results of Intergroup C9741, most notably in women with estrogen-receptor (ER)-negative disease.