Micrograph showing DLBCL
Results from the SCHOLAR-1 study revealed poor outcomes of salvage therapy in patients with refractory diffuse large B-cell lymphoma (DLBCL).
This retrospective study included data on patients enrolled in 2 randomized trials and 2 academic databases.
The patients had primary refractory disease, were refractory to second-line or later therapy, or had relapsed within 12 months of autologous stem cell transplant (ASCT).
Twenty-six percent of patients responded to salvage therapy, with 7% achieving a complete response (CR).
The median overall survival (OS) was 6.3 months, and 20% of patients were still alive at 2 years’ follow-up.
Christian Gisselbrecht, MD, of Saint Louis Hospital in Paris, France, and his colleagues reported these findings in Blood. SCHOLAR-1 was funded through an unrestricted grant from Kite Pharma.
“SCHOLAR-1 demonstrates the uniformly poor treatment outcomes for patients with aggressive non-Hodgkin lymphoma and emphasizes the need for breakthrough therapies for these refractory patients,” Dr Gisselbrecht said.
Patient characteristics
The study included pooled, patient-level data from 2 phase 3 trials and 2 databases:
- The Canadian Cancer Trials Group study LY.12 (n=219)
- The Lymphoma Academic Research Organization’s CORAL study (n=170)
- A cohort from MD Anderson Cancer Center (n=165)
- A cohort from the Molecular Epidemiology Resource of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (n=82).
There were a total of 636 patients who met criteria for refractory DLBCL, which included primary mediastinal B-cell lymphoma and transformed follicular lymphoma.
Twenty-eight percent of patients were primary refractory, 50% were refractory to second-line or later therapy, and 22% had relapsed within 12 months of transplant.
The patients’ median age was 55 (range, 19-81), and 64% were male. Seventy-three percent had an ECOG performance status of 0-1, 14% had a status of 2-4, and 13% were missing this data. Seventy-two percent of patients had stage III-IV disease, 27% had stage I-II disease, and less than 1% were missing this data.
Treatments
The MD Anderson cohort included patients who were relapsed/refractory to initial rituximab-containing chemotherapy, had failed salvage platinum-containing chemotherapy, and received a second salvage therapy at MD Anderson.
The University of Iowa/Mayo Clinic cohort included unselected, newly diagnosed patients with lymphoma who entered prospective documentation of primary and subsequent treatments and outcomes.
In the LY.12 study, patients were enrolled upon relapse after anthracycline-containing therapy and randomized to 1 of 2 salvage regimens, with a goal of consolidative ASCT.
The CORAL study enrolled patients in their first relapse or whose lymphoma was refractory to first-line therapy. They were randomized to 1 of 2 salvage regimens, with a goal of consolidative ASCT.
In the LY.12 and CORAL studies, eligible patients with CD20+ lymphoma were randomized to rituximab maintenance or observation post-ASCT.
Response
In all, 523 patients were evaluated for response. The overall response rate (ORR) was 26%, with a 7% CR rate and an 18% partial response rate.
Among patients with primary refractory disease, the ORR was 20%, and the CR rate was 3%.
Among patients who were refractory to second-line or later therapy, the ORR was 26%, and the CR rate was 10%.
Among patients who relapsed after transplant, the ORR was 34%, and the CR rate was 15%.
Survival
A total of 603 patients were evaluated for survival.
The median OS from the start of salvage therapy was 6.3 months (range, 5.9-7.0). The 1-year OS rate was 28%, and the 2-year OS was 20%.
Among primary refractory patients, the median OS was 7.1 months (range, 6.0-8.1), 1-year OS was 29%, and 2-year OS was 24%.
Among patient who were refractory to second-line or later therapy, the median OS was 6.1 months (range, 5.2-7.0), 1-year OS was 26%, and 2-year OS was 17%.
Among patients who relapsed after transplant, the median OS was 6.2 months (range, 5.2-7.6), 1-year OS was 32%, and 2-year OS was 19%.
“Although 60% to 70% of non-Hodgkin lymphoma patients survive 5 years after rituximab-based chemotherapy and autologous stem cell transplant, nearly half of them either do not respond or relapse shortly after transplant,” Dr Gisselbrecht noted.
“SCHOLAR-1 provides a rigorous measure of outcomes for these patients who do not benefit from currently available therapies, and this landmark study will serve as an important historical control for evaluating new therapeutic candidates in the field of non-Hodgkin lymphoma.”
