CHICAGO – New recognition of the prognostic value of cytogenetic factors, minimal residual disease activity, and Philadelphia chromosome–like signature could improve the treatment and outcomes of acute lymphoblastic leukemia (ALL), according to Anjali Advani, MD.
CD20
About 80% of ALL is B-cell ALL and the majority of patients have pre–B-cell ALL, Dr. Advani, a hematologist and director of the inpatient leukemia program at the Cleveland Clinic, said at the American Society of Hematology Meeting on Hematologic Malignancies.
“And on the B lymphoblast, many antigens are expressed, including CD19, CD20, and CD52,” she said.
Rituximab, a drug often used for the treatment of lymphoma, is a chimeric monoclonal antibody against the protein CD20, which is expressed in 41% of ALL patients.
“Interestingly, CD20 expression in ALL has been associated with an adverse prognostic impact, which suggests that targeting this may potentially improve outcomes in these patients,” Dr. Advani said.
In fact, a recent randomized study by Sébastien Maury, MD, of the University of Paris-Est, and his colleagues, demonstrated that adding 16-18 doses of rituximab to a Berlin-Frankfurt-Münster (BFM)–based chemotherapy in Philadelphia chromosome (Ph)–negative patients aged 18-59 years with CD20-positive pre–B-cell ALL improved 2-year event-free survival from 52% to 65%. The data are consistent with those from prior studies, including a German study that showed a higher degree of minimal residual disease (MRD) negativity in patients treated with rituximab, she noted (N Engl J Med 2016;375:1044-53).
While the study by Dr. Maury and his colleagues didn’t look at MRD, that may offer an explanation for the improved event-free survival in their study, Dr. Advani suggested.
MRD
Minimal residual disease has become a standard part of practice in ALL, but pediatric ALL led the way in using early MRD measurement for risk-stratifying therapy, and it has taken a bit longer for it to be incorporated in the adult disease realm, Dr. Advani said.
Either flow cytometry or polymerase chain reaction (PCR) amplification can be used to measure MRD, she noted.
In one of the larger studies done in adults, researchers used PCR to look at MRD at two time points and stratified patients into three risk groups, including low, intermediate, and high risk (Blood. 2006 Feb 1;107:1116-23).
Measuring MRD at those two time points “clearly separated the prognosis of patients not only in terms of disease-free survival but [in] overall survival,” she said. “So that’s why, for ALL, this has really become very important.”
In the United States, where flow-based cytometry is used more, it is necessary to find a properly equipped laboratory that can provide reliable results, she added. “For example, at our center we actually send our MRD to Fred Hutchinson [Cancer Center in Seattle].”
Johns Hopkins [Baltimore] also has such a lab, and both can arrange to accept send-outs, she said.
The other “really exciting thing” in regard to MRD in ALL is the recent approval of blinatumomab for MRD-positive ALL, she said.
In a study of 113 evaluable patients who were treated with the monoclonal antibody, 78% achieved complete molecular response (Blood. 2018 Apr 5;131:1522-31).
“And probably most importantly, when they looked at those patients who responded to blinatumomab in terms of MRD, these patients had, again, not only improved relapse-free survival but also increased overall survival,” she said. “I think this really explains why in ALL, we are measuring MRD and how it can really impact these patients.”
One of the remaining questions that will be important to address going forward is whether patients with MRD-positive ALL should continue to be considered for transplant; some of these studies have shown “very, very good outcomes” in patients who have not been transplanted, she noted.