The American Society of Hematology held its 50th Annual Meeting in San Francisco in December, hosting more than 21,000 hematologists, clinicians, and scientists from around the world. This grand forum presented a superb educational program, cutting-edge scientific sessions, and peer-reviewed oral and poster presentations about the latest and most exciting developments in scientific research. The following represents just a few of the meeting’s highlights. For more, visit http://abstracts.hematologylibrary.org/content/vol112/issue11. Romidepsin Shows Encouraging Activity in Heavily Pretreated Refractory Cutaneous T-cell Lymphoma
The novel histone deacetylase inhibitor (HDAC) romidepsin showed encouraging activity in treatment-refractory cutaneous T-cell lymphoma in an international, multicenter, open-label, Phase IIb registration trial, according to Youn Kim, MD, Stanford Comprehensive Cancer Center, Stanford, CA. The noteworthy activity of romidepsin, as well as the favorable safety profile for the drug, suggest that it will be further evaluated as a potential treatment for advanced, refractory cutaneous T-cell lymphoma. Vorinostat was the first HDAC inhibitor to be approved for cutaneous T-cell lymphoma. Romidepsin, a potent pan-HDAC inhibitor, is active against multiple HDAC isoforms. The drug has exhibited activity in both cutaneous T-cell lymphoma and peripheral T-cell lymphoma.
In 72 evaluable patients, overall disease control rate was 78% (overall response rate [ORR] 42%, complete response [CR] 8%, partial response [PR] 33%, stable disease [SD] 36%). An intent-to-treat (ITT) analysis of 96 patients who entered the study (regardless of whether they received treatment) showed an overall disease control rate of 63% (ORR 34%, CR 6%, PR 28%, SD 29%). Romidepsin achieved responses in advanced stage cutaneous T-cell lymphoma; ORR was 48% in patients with stage > IIB disease, and four of eight patients with Sezary syndrome achieved PR. Duration of response was noteworthy in these heavily pre-treated patients who received a median of three prior systemic therapies, according to Kim. The median time to disease progression was 8.3 months in the ITT analysis and 17.7 months in 72 evaluable patients.
Pruritus, as assessed by a decrease in visual analogue scale (VAS) of at least 30mm, was evaluated as a secondary outcome in this trial. The majority of patients experienced relief of moderate or severe pruritus, despite not being given concomitant steroids or antihistamines. Romidepsin improved pruritus in 33 of 52 patients (63%) with moderate to severe pruritus at baseline: 17 patients who achieved CR or PR and 16 patients who did not achieve overall response. Thus, although a proportion of patients don’t achieve CR or PR on romidepsin, they may achieve symptomatic relief of pruritus.
Romidepsin was well tolerated by this difficult-to-treat population. Grade 3 or 4 adverse events occurred as single occurrences in 15% of patients. The most common grade 3 or 4 events included fatigue (6%), nausea (2%), diarrhea (1%), and vomiting (1%). The most frequently reported treatment-related events of all grades were nausea (56%), fatigue (30%), vomiting (26%), anorexia (20%), diarrhea (14%), headache (14%), loss of taste (13%), persistent abnormal taste (11%), and thrombocytopenia (10%). The study allayed concern about cardiac toxicity with an HDAC inhibitor, since minimal or no effect on the QTc interval was observed.FCR New Standard of Care for Untreated and Treatment-refractory CLL
Rituximab added to fludarabine and cyclophosphamide (FCR) represents a new standard of care for previously untreated patients with chronic lymphocytic leukemia (CLL), as well as those with relapsed/refractory CLL, according to two large randomized controlled clinical trials comparing FCR to standard chemotherapy with FC.
The first study (CLL 8) evaluated 817 previously untreated patients with advanced CLL. About three-quarters were male, about two-thirds were Binet Stage B, and median age was 61 years. First-line treatment with FCR was superior to FC for response rate and progression-free survival. Patients in the FCR arm had a 44.5% complete response (CR) rate compared with 22.9% in the FC arm (P=.01). The partial response (PR) rate was lower in the FCR arm (3.3% versus 8.8% for FC), which was attributed to the higher CR rate with FCR.
“A higher CR translates to longer time to progression,” explained Michael Hallek, MD, of the University of Cologne in Cologne, Germany, who led this trial on behalf of the German CLL Study Group.
At a median observation time of 25.5 months, median progression-free survival was 42.8 months for FCR versus 32.3 months for FC, a highly statistically significant difference favoring the addition of rituximab (P=.000007).