The monoclonal antibody rituximab (Rituxan) improves event-free survival (EFS) among adults with CD20-positive B-cell acute lymphoblastic leukemia (ALL), according to authors of a phase III clinical trial conducted in France and Switzerland.
The monoclonal antibody rituximab (Rituxan) improves event-free survival (EFS) among adults with CD20-positive B-cell acute lymphoblastic leukemia (ALL), according to authors of a phase III clinical trial conducted in France and Switzerland. Their findings were published in The New England Journal of Medicine.
“This randomized study showed that the addition of rituximab to standard chemotherapy significantly improved event-free survival among adults with CD20-positive ALL,” reported SÃ©bastien Maury, MD, PhD, of the Institut Universitaire d’HÃ©matologie in Paris, France, and coauthors.
The improved EFS was attributable to a reduced cumulative incidence of relapses and no concomitant increase in toxicity or mortality, the authors wrote.
“Although more patients in the rituximab group than in the control group underwent allogenic stem-cell transplantation during the first remission, the reduced incidence of relapse and improvement in event-free survival cannot be clearly explained by a potential benefit of transplantation,” they reported, listing three reasons for that conclusion: most transplantation-associated fatalities occurred in the rituximab group; the relationship remained significant in sensitivity analyses that controlled for transplantation status; and the association remained significant after statistical adjustment for transplantation.
Rituximab targets the CD20 protein, which is expressed on the cell surfaces of most B lymphocytes. Rituximab is associated with improved outcomes among patients with non-Hodgkin lymphoma and prior cohort studies have hinted that it might similarly benefit patients with adult B-cell acute lymphoblastic leukemia (ALL).
The Group for Research on Adult Acute Lymphoblastic Leukemia 2005 (GRAALL-2005) clinical trial was undertaken at 65 cancer centers in France and Switzerland. Between 2006 and 2014, the research team enrolled 209 adult patients with CD20-positive, Philadelphia chromosome (Ph)-negative B-cell ALL, and randomly assigned 105 to receive rituximab with chemotherapy and 104 to a control group that received chemotherapy alone.
Patients in the rituximab group received the antibody for 16 to 18 infusions, during all phases of treatment, including maintenance therapy-an empirical schedule based on rituximab treatment experiences among patients diagnosed with non-Hodgkin lymphoma.
At a median followup of 30 months, EFS was longer for patients in the rituximab group (hazard ratio [HR], 0.66; 95% CI: 0.45-0.98; P = .04) and the 2-year EFS rates for the rituximab and control groups were 65% and 52%, respectively.
“A direct effect of rituximab, mediated by its binding to leukemic cells, is suggested by the more pronounced benefit observed in patients with higher levels of CD20 expression on their leukemic blasts,” the authors concluded. An indirect mechanism might have also been possible, because fewer patients in the rituximab group experienced allergic reactions to asparaginase, they acknowledged-possibly indicating that these patients received higher asparaginase doses during treatment. But there was similar adherence to asparaginase treatment in both study groups, they were quick to add.
Other than a significantly lower rate of allergic reaction among patients in the rituximab group (P = .002), severe adverse event rates were not significantly different between the study groups.
It was not clear whether or not patients who were excluded from the study because their blasts’ surface expression of CD20 fell below the 20% threshold that was used to define CD20 positivity, would also have benefited from rituximab, the authors noted.