Myelodysplastic Syndromes

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.

ORLANDO - The thalidomide analog lenalidomide (CC-5013, Revlimid) significantly reduced the need for blood transfusions in patients with myelodysplastic syndrome (MDS) who had interstitial deletions in band 31 of the long "q" arm of chromosome 5, the most common cytogenetic abnormality in MDS, a multicenter phase II study has found. More than two-thirds of patients with 5q31 deletions achieved transfusion independence in response to the drug, and 44% had a complete cytogenetic response, Alan List, MD, reported at the American Society of Clinical Oncology 41st Annual Meeting (abstract 5).

Priming of leukemic cells with cytokines may enhance the efficacy of cell-cycle chemotherapy. In this study, we utilized these synergistic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]), hydroxyurea, and low-dose cytosine arabinoside to treat elderly patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). In a single-institution, retrospective study, we evaluated 94 treatments with concomitant hydroxyurea, cytosine arabinoside, and GM-CSF between the years of 1997 and 2003 in high-risk elderly patients with AML or MDS. A total of 80% of patients received all of the GM-CSF doses; 78% of patients received all of the cytosine arabinoside doses. Adverse events were minimal. No patient developed mucositis or alopecia. The most common adverse event was neutropenic fever, which was noted in 57% of patients. Twenty-one percent of patients remained neutropenic after treatment until death or relapse. Sixty-eight percent of patients reached an absolute neutrophil count of greater than 1,000 μL in a median of 33.5 days. Our data show an overall response rate of 52%, with a complete response rate of 39% and a partial response rate of 13%. Overall, our study showed that low-dose cytosine arabinoside given by continuous infusion together with continuous infusion GM-CSF and hydroxyurea was well-tolerated and effective in treating elderly AML and MDS patients who were not eligible for standard induction therapy.

SAN DIEGO, California-One in four Hodgkin’s disease (HD) patients has become a parent since participating in prospective trials of an experimental first-line regimen, known as Stanford V, designed to reduce toxicity from chemotherapy and radiotherapy.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

SAN DIEGO-There have been no reported cases of treatment-related myelodysplastic syndrome and acute myeloblastic leukemia (tMDS/tAML) in patients with low-grade non-Hodgkin’s lymphoma (NHL) treated initially with the Bexxar therapeutic regimen (tositumomab and iodine-131 tositumomab).

CHICAGO-Adjuvant therapy with epirubicin (Ellence) followed by cyclophosphamide, methotrexate, and 5-fluorouracil (ECMF) prolongs relapse-free survival and overall survival with only modest toxicity in patients with early-stage breast cancer and should replace upfront CMF as standard therapy in that setting, Christopher J. Poole, MD, said at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 13).

BETHESDA, Maryland-Members of the FDA’s Oncologic Drugs Advisory Committee (ODAC) gave a mixed review to Corixa’s Bexxar (tositumomab and iodine I-131-tositumomab), a radioactive-labeled monoclonal antibody intended to treat certain non-Hodgkin’s lymphoma (NHL) patients.