SAN FRANCISCOPatients with acute myeloid leukemia
(AML) in first relapse who achieve remission with the antibody gemtuzumab
ozogamicin (Mylotarg) before undergoing stem cell transplantation have
prolonged disease-free survival, according to research presented at the 42nd
Annual Meeting of the American Society of Hematology (ASH).
Early data from clinical studies conducted at Fred Hutchinson
Cancer Research Center and other centers suggest that patients who respond to
pretransplant therapy with gemtuzumab can receive curative therapy in the form
of hematopoietic stem cell transplantation.
"Mylotarg is a drug that enables patients to receive
definitive therapy," said Eric Sievers, MD, assistant professor of
pediatrics, University of Washington, and assistant member, Fred Hutchinson
Cancer Research Center.
Gemtuzumab is a humanized anti-CD33 antibody linked to
calicheamicin, a potent antitumor antibiotic. It is FDA approved for the
treatment of CD33-positive AML in patients age 60 and older who are in first
relapse and are poor candidates for cytotoxic therapy. Expression of CD33 is
restricted to hematopoietic cells and absent from pluripotent stem cells.
The study included 22 patients with AML in first relapse who
achieved remissions with gemtuzumab administered as a single agent and then
underwent hematopoietic stem cell transplantation: 11 allogeneic and 11
A majority of patients were alive without leukemia 1 year after
the transplant (see Figure 1). At the time of data cutoff, the median
relapse-free survival for the 22 patients was 17.4 months.
One-year survival of responding patients was highest for those
who received allogeneic stem cell transplants (60%), compared with a 40%
survival rate for autologous transplant patients (Figure 2).
"Of 188 AML patients enrolled in the pivotal phase II
trials of Mylotarg, 58 responded to Mylotarg treatment but only 22 received
subsequent hematopoietic stem cell transplantation, perhaps because of concerns
regarding the intensity of the treatment," Dr. Sievers told ONI. "Our
data support the overall safety and efficacy of hematopoietic stem cell
transplantation for patients who achieve second remissions with Mylotarg."
Gemtuzumab offers patients a "reasonably deep
remission" that is sufficient to deliver patients to successful
transplantation, he said.
The incidence of fatal hepatic veno-occlusive disease in these
patients was reasonably low. One of the 22 responding transplant patients (5%)
succumbed to veno-occlusive disease, as did 2 of 13 (15%) nonresponding
patients who underwent transplantation in refractory first relapse.
"This study shows that patients with relapsed AML can be
safely salvaged with a combined Mylotarg-transplant approach," Dr. Sievers