New York, NY—A new study suggests that cancer testis antigens (CTAs) should be therapeutically targeted in patients with multiple myeloma (MM).
The study revealed that CTAs are frequently expressed in newly diagnosed MM patients, the presence of certain CTAs can help predict poor survival, and MM patients experience spontaneous antibody responses to CTAs. Adam Cohen, MD, of Fox Chase Cancer Center in Philadelphia, presented this research at Lymphoma & Myeloma 2009, where it was deemed “the best myeloma abstract.”
Dr Cohen and his colleagues enrolled in their study 67 newly diagnosed MM patients. Patients received an induction regimen consisting of thalidomide, doxorubicin, and dexamethasone, and 54 patients went on to receive autologous stem cell transplant.
The researchers assessed CTA expression in cryopreserved pretreatment bone marrow plasma cells. Seventy-seven percent of patients had at least 1 CTA. MAGE-A3 was present in 52% of patients, SSX1 in 40%, CT7 in 29%, CT10 in 25%, NY-ESO1 in 21%, and SSX5 was expressed in 17% of patients. Twenty-nine percent of patients had 3 or more CTAs.
“So the main question was, what was the prognostic significance of these findings?” Dr Cohen said. “We looked at overall survival on the basis of the presence or absence of each of these antigens or based on the absolute number of antigens that were expressed. What we found were 2 antigens that really seemed to stand out, in terms of having prognostic significance.”
Patients who expressed MAGE-A3 or NY-ESO1 had worse overall survival (OS) than patients who expressed other CTAs. OS was a median of 66 months in patients with MAGE-A3 and 65 months in patients with NY-ESO1, while OS was not reached in the other patients.
The poor OS observed in patients with MAGE-A3 and NY-ESO1 was independent of disease stage, cytogenetic abnormalities, and response to induction therapy.
Dr Cohen and his colleagues then assessed pre- and post-treatment sera for antibody responses. Forty-six patients had sera available. Six patients had antibody responses to NY-ESO1. Of these patients, 2 also demonstrated responses to CT7, 1 had response to CT10, and 1 had response to SSX4.
“[A]ll these patients had immunity to NY-ESO1, but in 2 patients, number 30 and 54, there actually was no NY-ESO1 expression in their bone marrow,” Dr Cohen said. “[B]oth of these had extramedullary disease, and so the suggestion was that there may be an additional source of the NY-ESO1 antigen.”
This theory was supported by the fact that these 2 patients had soft tissue plasmacytomas. And the presence of NY-ESO1 antibody was significantly associated with soft tissue involvement, as 67% of NY-ESO1 antibody-positive patients had soft tissue plasmacytomas.
In addition, antibody response against NY-ESO1 was associated with poor OS. NY-ESO1 antibody-positive patients had an OS of 21 months, while OS was not reached in NY-ESO1 antibody-negative patients.
Dr Cohen presented these data at Lymphoma & Myeloma 2009, which took place October 22-24.
