Australian data from a conjugate therapy access program for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) highlights the discrepancy between real world outcomes and clinical trial outcomes.

The observational study, published in eJHaem [link here], included 58 patients with confirmed RR-DLBCL or high-grade B-cell lymphoma (HGBL) with rearrangement of MYC and BCL2 / BCL6 who received at least one cycle of polatuzumab vedotin on a compassionate access scheme.

Most patients received polatuzumab with bendamustine and rituximab (pola-BR, 58.8%), 23.5% received pola with rituximab, 9.8% received pola with bendamustine, and 7.8% received pola monotherapy.

More than half of patients had received ≥3 prior lines of therapy.

The study found that only 28.3% completed all six planned cycles of therapy while progressive disease was the main reason for discontinuation (71.1%). Treatment-related adverse effects included anaemia (70.6%) and thrombocytopenia (58.8%).

The study found the median PFS was 2.3 months and OS 3.5 months.

“Median OS in those receiving pola-BR was 5.9 months (95% CI: 2.5–9.7 months) versus 3.4 months (95% CI: 1.8–4.6 months) in pola monotherapy plus pola-R treated patients (p = 0.29),” it said.

“The ORR in evaluable patients was 45.8%, including complete response (CR) in 25% (12/48) and partial response (PR) in 20.8% (10/48). 10.4% achieved stable disease (5/48) and 43.8% (21/48) had progressive disease.”

The study noted that 71% of patients in the study would have been ineligible for the registrational G029365 trial [link here] which found pola-BR resulted in a significantly higher CR rate and reduced the risk of death by 58% compared with BR in patients with transplantation-ineligible R/R DLBCL.

Reasons for trial ineligibility included a significant comorbidity (32.8%), eligible for autologous SCT (25.9%), transformed from indolent disease (22.4%) and elevated creatinine (19.0%).

“The median PFS and OS were dismal in our Australian population, considerably worse than the median PFS and OS of 9.2 months and 12.4 months respectively reported by Sehn et al. in the GO29365 study,” the investigators said.

“The substantial proportion of ineligible patients in our cohort (74%) likely contributes to this, although we found no statistically significant difference in outcomes between eligible and ineligible patients within our population.”

The study, whose senior investigators included Professor Stephen Opat and Associate Professor Eliza Hawkes from Monash University, said the reasons for trial ineligibility also translated into limited use of intensive salvage therapy and few treatment options overall for these patients.

“Discordant results between registrational clinical trials and routine care are increasingly common, risking the creation of unrealistic expectations and treatment in the context of futility,” they concluded.

“The importance of recruiting representative populations to clinical trials to ensure results are relevant to the majority of routine care patients, and communication of accurate expectations to patients is imperative in future research.”