Early myeloablative therapy may benefit subset of high-risk non-Hodgkin’s lymphoma patients

In patients with diffuse large B-cell lymphoma, the survival rate remains about 60% among those in an International Prognostic Index (IPI) category of high-intermediate risk or high risk. Thus, the results of this study of early myeloablative treatment bring hope for high-risk patients, but also merit discussion as to whether they can be applied broadly, in view of the greater toxicity and what has been learned in the years since this study was initiated.

Going forward, it should be possible to better select patients for enrollment in trials of early myeloablative therapy, and the selection should not be based simply on the IPI risk category. We must identify patients at highest risk for nonresponse to standard treatment (about 15% of patients) and those at highest risk for relapse (about 25% of patients), so that they can be given alternative treatments; we must also give patients without these risk factors an excellent chance of cure with easier-to-administer and less-toxic chemotherapeutic agents.

One possibility is to select patients who have poor prognoses with standard treatment, such as those with "double-hit" lymphomas characterized by deregulation of the MYC proto-oncogene in association with overexpression of BCL2. These lymphomas can be easily identified by immunohistochemical analysis of tumor samples and may account for 20% of cases of diffuse large B-cell lymphoma, regardless of IPI risk category.

Alternatively, the subset of patients who have negative results on positron emission tomographic scans performed after a few cycles of R-CHOP have an excellent prognosis with standard treatment. Even when such patients are in a high IPI risk category, myeloablative therapy may be unnecessary for them.

Dr. Noel Milpied is chief of hematology and cellular therapy at the University Hospital of Bordeaux, France. He made his remarks in an editorial that accompanied the published study (N. Engl. J. Med. 2013;368:1681-2). Dr. Milpied reported financial relationships with multiple pharmaceutical companies.