Poor Outcomes in Elderly Patients After Treatment Failure in B-Cell Lymphomas

Elderly patients, including those treated with an R-CHOP regimen, tend to have poor outcomes regardless of salvage therapy.

A study examining treatment and outcome patterns following failure of initial treatment for B-cell lymphoma found that rituximab can improve outcomes regardless of which initial therapy was used, but elderly patients, including those treated with an R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen, tend to have poor outcomes regardless of salvage therapy. MYC rearrangement is an adverse prognostic factor, the study found.

“The addition of the anti-CD20 antibody rituximab to chemotherapy improved the survival of patients with aggressive B-cell lymphomas of all ages and prognostic subgroups,” wrote study authors led by Bertram Glass, MD, of Helios Klinikum Berlin-Buch in Berlin. “Nonetheless, about one-third of patients experience progression during or relapse after first-line therapy.”

This study examined patient and treatment characteristics for patients in the RICOVER-60 trial, which included 1,222 B-cell lymphoma patients between the ages of 61 and 80 years. Of those, 301 experienced treatment failure (24.6%), and 297 were available for this analysis. The results were published in Annals of Oncology.

Failure was more common in those who had received CHOP chemotherapy (31.2%) than in those who received R-CHOP (18.0%). The patients were followed for a median of 26.5 months after failure.

The 2-year overall survival (OS) rate was 31.7%, and the median OS was 9.4 months. Patients treated with R-CHOP had significantly shorter survival, with a 2-year OS rate of 23.0% compared with 36.4% for those treated with CHOP (P = .016).

MYC translocations were a significant prognostic risk factor for OS after treatment failure in all patients, with a relative risk (RR) of 2.6 (95% CI, 1.3–5.1; P = .006), and for patients treated with CHOP, with an RR of 4.8 (95% CI, 2.1–11.2; P < .001). In those patients with MYC translocation at diagnosis, rituximab reduced the risk of treatment failure from 58.8% to 26.3%.

Patients with early treatment failure, within 12 months, had poorer survival. The 2-year OS rate was 24.8% for all patients with early failure, and 29.4% for those treated with first-line CHOP. First-line CHOP patients with late failure had a 2-year OS rate of 55.1%. Similar results were seen in R-CHOP–treated patients, with a 2-year OS rate of 15.9% after early treatment failure and 39.9% after late failure.

A total of 128 patients received rituximab as part of salvage therapy, and 77.3% of these patients were rituximab-naive at the point of salvage treatment. Repeated administration of rituximab yielded a better OS, with a 2-year rate of 49.6% compared with 19.1% for those treated with rituximab for the first time at salvage therapy. A multivariate model showed that treatment with rituximab as part of salvage therapy was significantly associated with reduced mortality risk, with an RR of 0.4 (95% CI, 0.3–0.6; P < .001).

“Overall, the outcome of second-line treatment of elderly patients with refractory and relapsed aggressive B-cell lymphoma is disappointing and worse than in younger patients regardless of the modality chosen,” the authors wrote. “New drugs and treatment modalities with the potential to change the dismal outlook for elderly patients with aggressive B-cell lymphomas are eagerly awaited.”