Late Relapse a Possibility Even in DLBCL Patients Disease Free at 2 Years

Late relapses occurred more commonly among patients with DLBCL with concurrent indolent lymphoma at initial diagnosis and those with GCB subtype.

Only about 10% of patients with diffuse large B-cell lymphoma (DLBCL) who achieved event-free survival at 2 years (EFS24) after immunochemotherapy experienced a late relapse at 5 years, according to the results of a recent study. However, late relapses occurred more commonly among patients with DLBCL with concurrent indolent lymphoma at initial diagnosis and those with germinal center B-cell–like (GCB) subtype.

“Our results have implications for clinical practice and clinical trial design,” wrote researcher Yucai Wang, MD, PhD, of the Mayo Clinic in Rochester, Minnesota, and colleagues, in the Journal of Clinical Oncology. “It is critical to counsel patients that achieving EFS24 does not mean a cure and the late-relapse risk is not trivial, with particular attention not only to those with advanced stage or a high IPI score (higher risk of DLBCL relapse) but also those with concurrent indolent lymphoma or the GCB subtype (higher risk of indolent lymphoma relapse).”

Wang and colleagues conducted a prospective study of 1,324 patients with newly diagnosed DLBCL who were treated with immunochemotherapy from 2002 to 2015. In the study, they looked at the rate of late DLBCL and indolent lymphoma relapses.

At diagnosis, 87% of patients had DLBCL alone, and 13% had concurrent DLBCL and indolent lymphoma. Of the 1,324 patients, 847 achieved EFS24. The rate of late relapse was 6.9% at 3 years, 9.3% at 5 years, and 10.3% at 8 years.

Patients with concurrent indolent lymphoma and DLBCL had about double the rate of late relapse compared with patients with DLBCL alone (13.3% vs 5.7% at 3 years and 15.4% vs 8.1% at 5 years; P < .01). According to the researchers, relapses of indolent lymphoma accounted for this difference in relapse. Among patients with late relapse of DLBCL, the rates of late relapse were similar among patients with DLBCL alone at diagnosis and those with concurrent indolent lymphoma. However, among patients with indolent lymphoma relapse, the rates of relapse were higher in patients with concurrent DLBCL and indolent lymphoma at diagnosis compared with patients with DLBCL alone (5.3% vs 1.4% at 3 years and 7.4% vs 2.1% at 5 years; P < .01).

Additionally, among those patients with DLBCL alone, the researchers saw a trend for a higher incidence of late relapse in patients with GCB subtype compared with non-GCB subtype (5.6% vs 3.0% at 3 years and 8.8% vs 4.0% at 5 years; P = .05). This difference was also driven by relapse of indolent lymphoma, the researchers noted.

Patients who relapsed with DLBCL had worse post-relapse survival than those who relapsed with indolent lymphoma (median, 29.9 months vs not yet reached; P < .01).

In a podcast interview with the Journal of Clinical Oncology, Ann LaCasce, MD, MMSc, of Dana-Farber Cancer Institute, emphasized the importance of continued follow-up of patients with DLBCL, where visits often become less frequent for patients who remain in remission beyond the 5-year mark.

“The likelihood of identifying recurrent disease in an asymptomatic patient with a normal physical exam is extremely low,” LaCasce said. “Nonetheless, given that recurrences do occur, educating survivors and their physicians, including primary care providers, to be vigilant for the development of persistent symptoms without clear explanation, as well as B symptoms and lymphadenopathy, is important. Setting expectations with patients is also essential, as is caution in using the term ‘cure.’”