The 53rd Annual Meeting of the American Society of Hematology (ASH) convened in San Diego, CA, December 10-13, 2011. The meeting was attended by more than 21,000 participants from around the globe. The scientific program, which typically covers all areas of benign and malignant hematology, included presentations on cutaneous T-cell lymphomas (CTCL) and highlighted advances in basic research, new treatments, and symptom management.
Results of a Phase II clinical trial of intravenous pegylated liposomal doxorubicin (PLD) followed by oral bexarotene (Targretin) in patients with advanced CTCL were presented by Dr. Strauss of Memorial Sloan Kettering Cancer Center (MSKCC) and colleagues. PLD is a new formulation of the old anti-cancer drug doxorubicin (Adriamycin), which is safer and has better skin distribution than the unmodified drug, and has shown promise in CTCL. Patients received 16 weeks of PLD followed by 16 weeks of oral bexarotene. In total, 37 patients with advanced CTCL (including Sezary syndrome) were treated, with responses observed in about 40%. Some responses were durable, but in most patients the disease came back relatively quickly (5 months). Moderate to severe toxicity was observed in a third of the patients. The investigators could not tell if the addition of bexarotene was beneficial. Overall, LPD is an active drug, but should be considered in patients with advanced CTCL who do not have other treatment options and are not eligible for clinical trials. Access to the drug may also be problematic due to a recent shortage.
Dr. Christiane Querfeld of MSKCC and colleagues presented results of a Phase II clinical trial of the new oral drug lenalidomide (Revlimid) in patients with CTCL. As observed in other types of lymphoma and leukemia, at higher doses the drug caused inflammation and flare up reactions, requiring dose adjustments. The response rate was about 30%, which is comparable to other drugs recently approved for T-cell lymphoma, such as romidepsin (Istodax), vorinostat (Zolinza), and pralatrexate (Folotyn). Side effects were manageable and not severe. Lenalidomide remains experimental in CTCL.
Finally, investigators from New York University presented their post-marketing experience with the newly-approved drug romidepsin (Istodax) in the management of CTCL. In a group of heavily pre-treated patients that included Sezary syndrome, they observed very satisfactory responses and tolerable toxicity. There were no significant cardiovascular side effects and responses were observed in patients who had been previously treated with other HDAC inhibitors. Improvement of pruritus (itching) was consistently observed.
In the important fight to improve symptom control in CTCL, a group of investigators from Emory, Boston, and Stanford University introduced a new Quality of Life (QoL) instrument. They collected detailed information using four different methods (one interview and three self-administered questionnaires) and compared them. A representative sample of CTCL patients of different age, gender and ethnicity was studied. The investigators observed that no single questionnaire captured the whole gamut of concerns and symptoms. A majority of patients expressed concern with pruritus and worries that the condition was serious or would get worse. Importantly, the open-ended interviews revealed that patients had concerns not always captured by the questionnaires, such as: 1) treatment was time-intensive; 2) dry mouth and skin; 3) frustration at delay in diagnosis; and 4) burden on family. The researchers will continue to work on improved QoL instruments based on these data.
Several advances in laboratory research in CTCL were presented.
Dr. Salvia Jain of New York University Cancer Center presented a new bio-luminescent animal model of Sezary syndrome that allows for direct tracking of human disease in the mouse and will be very helpful in designing and assessing new treatment strategies for this aggressive type of CTCL. This important work, completed under the mentorship of Dr. Owen O’Connor, was noted and recognized by the Cutaneous Lymphoma Foundation with Dr. Jain being nominated as the first recipient of its new ASH Young Investigator Award.
Another laboratory presentation that is sure to have a significant impact on the future treatment of CTCL was given by Dr. Wen-Kai Weng and colleagues from Stanford University. These investigators developed a sophisticated method to specifically identify and monitor extremely small numbers of residual CTCL cells in the blood of individual patients after bone marrow transplantation, observing in some cases a complete disappearance of all CTCL cells from the blood. This technology opens the door to a patient-specific quantification of tumor cells in the blood and a definition of minimal residual disease.
Finally, investigators from the University of Texas, MD Anderson Cancer Center studied the immune effects of the new anti-CCR4 monoclonal antibody KW-0761, which is showing promise in the treatment of CTCL, including Sezary syndrome. Using patient samples from a Phase I/II clinical trial, Dr. Xiao Ni and colleagues observed that the administration of KW-0761 led in many cases to a decrease in a subset of blood T-cells called Treg cells, which can dampen the host immune response against CTCL. These researchers, therefore, suggest that KW-0761, in addition to a direct anti-tumor effect, may have benefit in CTCL patients by decreasing the number of circulating Treg cells. While these results are very interesting, this hypothesis needs to be confirmed.