Welcome to OncoFacts for February, 2010. For this issue of OncoFacts, we are going to focus on some of the most interesting data presented at the American Society of Hematology (ASH) Annual Meeting. We will discuss some of the data presented at the ASH Annual Meeting in the areas of multiple myeloma, myeloproliferative neoplasms, and myelodysplastic syndrome (MDS). Next month, we will look at data from the ASH Annual Meeting regarding chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), and lymphomas.

Myelodysplastic Syndromes

Abstracts 2772 and 293
The International Prognostic Scoring System (IPSS) has been generally accepted among hematologists in the US since published by Peter Greenberg in 1997. Ten years later, Malcovati revised the IPSS system into the World Health Organization (WHO) Classification-Based Prognostic Scoring System (WPSS) system by adding the factor of transfusion dependency. The WPSS was further revised last year by Dell Porta. A more complex and detailed prognostic scoring system has also been described by the M. D. Anderson Cancer Center group taking into account additional factors including the degree of thrombocytopenia, age, leukocytosis, and performance status.

At the ASH Annual Meeting, Schanz et al broke myelodysplastic syndromes (MDS) cytogenetic abnormalities down into 4 prognostic groups (Abstract 2772) with median survival of 50.6 months, 25.7 months, 16 months, and 5.7 months, respectively. The worst cytogenetic prognostic group were those with complex karyotypes and >3 abnormalities.

In abstract 293, Michel Van Gelder and colleagues from the Netherlands searched the European Group for Blood and Marrow Transplantation (EBMT) database for patients with MDS/secondary acute myelogenous leukemia (sAML) having any chromosome 7 abnormalities and treated with allogeneic-SCT from 1981 to 2006, and 278 patients were identified. Sixty-three patients had a monosomal karyotype with at least 1 monosomy and at least 1 other cytogenetic abnormality. Median follow-up of patients alive at last follow-up was 5 years.

In multivariate analysis of numerous prognostic factors, monosomal karyotype highly significantly predicted for extremely poor outcome. Five-year incidences of relapse and non-relapse mortality were 52% and 48%, respectively. Five-year overall survival (OS) and relapse-free survival (RFS) for patients with a monosomal karyotype were both 0% compared to 37% and 34% for patients without a monosomal karyotype.

Abstracts 3797 and 2773
The standard of care for higher risk patients with MDS is azacitidine 75 mg/m² daily x 7 every 4 weeks. Decitabine 20 mg/m² daily x 5 every 4 weeks is an alternative regimen.

In abstract 3797, Mikkael Sekeres presented data from the AVIDA Registry, a longitudinal, multicenter, US patient registry that collects data from community-based hematology clinics on the history and management of patients with MDS treated with azacitidine.

Fifty-seven percent received azacitidine IV and 43% subcutaneously for a median of 4 cycles. Only 17% received azacitidine by the continuous 7-day schedule. Fifty-one percent received azacitidine for <7 days, 30% for 7 days with breaks in the schedule and 2% for >7 days.

In multivariate analysis, the following predicted for poor outcome: low hemoglobin (Hgb), low platelet count, high blast percentage, cytogenetic abnormalities, and low body mass index. Intravenous dosing appeared to be equi-efficacious to subcutaneous dosing without the problems of local cutaneous reactions.

In abstract 2773, Regina Garcia from Spain presented an analysis of data from a longitudinal multicenter patient registry of patients with MDS from community-based hematology clinics in Spain. They examined dosing schedules of patients with MDS treated with azacitidine under a compassionate use program. Three dosing regimens in 28-day cycles were evaluated: Group A received azacitidine daily x 5 (36% of patients), Group B received azacitidine days 1-5 plus days 8 and 9 (32%), and Group C received azacitidine days 1-7 (32%).

Data analysis demonstrated a higher percentage of patients with Eastern Cooperative Oncology Group (ECOG) performance status 2 or higher plus a higher number of patients who were intermediate-2 (Int-2) and high-risk in Group C.

Response rates were somewhat better and myelosuppression less with the continuous 7-day regimen.

Abstract 119
A final hypomethylating agent abstract that I would like to describe was presented by Dr Guillermo Garcia-Manero from M. D. Anderson Cancer Center. This was a randomized phase II study looking at 2 dosing schedules for decitabine in lower-risk patients with MDS. Patients with low-risk and intermediate-1 (Int-1) were randomized to subcutaneous decitabine 20 mg/m² daily x 3 days every 4 weeks or weekly x 3 weeks out of 4.

Fifty-four patients were evaluable: 32 in arm A (daily) and 22 in arm B (weekly). Hematologic improvement was seen in 22% in arm A and 9% in arm B. Over 60% became independent of both red blood cell (RBC) and platelet transfusions. Responses were significantly longer with the daily regimen as was the progression-free survival (PFS).

Abstract 944
Pierre Fenaux presented the results of MDS-004, a phase III study evaluating the efficacy of 2 doses (5 mg or 10 mg daily) of lenalidomide versus placebo in patients who were transfusion dependent with low or Int-1 MDS with del5q. The lower dose of 5 mg was given daily for 28 days out of each 28-day cycle. The higher dose of 10 mg was given for only 21 days out of the 28-day cycle. Many patients still required dose reductions.

The primary endpoint was transfusion independence (TI) for >26 weeks. Two hundred five patients were randomized, and 138 patients were evaluable. Results (as noted below) demonstrate higher response rates with the higher dose of lenalidomide, but dose reductions are fairly frequent in both lenalidomide arms.

References
Schanz J, Tuechler H, Solé F, et al. Cytogenetic risk features in MDS–Update and present state. Blood. 2009;114(22). Abstract 2772 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.

Van Gelder M, Schetelig J, Volin L, et al. Monosomal karyotype predicts poor outcome for MDS/sAML patients with chromosome 7 abnormalities after allogeneic stem cell transplantation for MDS/sAML. A study of the MDS subcommittee of the Chronic Leukemia Working party of the European Group for Blood and Marrow Transplantation (EBMT). Blood. 2009;114(22). Abstract 293 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.

Sekeres MA, Maciejewski JP, Donley DW, et al. A study comparing dosing regimens and efficacy of subcutaneous to intravenous azacitidine (ASA) for the treatment of myelodysplastic syndromes (MDS). Blood. 2009;114(22). Abstract 3797 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.

Garcia R, de Miguel D, Bailen A, et al. Different clinical results with the use of different dosing schedules of azacitidine in patients with myelodysplastic syndrome managed with community-based practice: Effectiveness and safety data from the Spanish azacitidine compassionate use registry. Blood. 2009;114(22). Abstract 2773 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.

Garcia-Manero G, Couriel DR, Tambaro FP, et al. A phase II randomized bayesian study of very low dose subcutaneous decitabine administered daily or weekly times three in patients with lower risk myelodysplastic syndrome (MDS). Blood. 2009;114(22). Abstract 119 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.

Fenaux P, Giagounidis A, Selleslag D, et al. RBC transfusion independence and safety profile of lenalidomide 5 or 10 mg in pts with low- or Int-1-risk MDS with Del5q: Results from a randomized phase III trial (MDS-004). Blood. 2009;114(22). Abstract 944 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.

<< Myeloproliferative Neoplasms

To enhance the abstracts presented here from the 2009 American Society of Hematology Meeting, there are 9 “Best of the Day” interviews with leading national and international hematologists and oncologists that are available in the Imedex E-Learning Center.

I hope that you have enjoyed this edition of OncoFacts and will look forward to next month’s edition.

OncoFacts™ Editor:

James Epstein, MD

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