乌鸦传媒

Postchemotherapy consolidation with atezolizumab (Tecentriq) led to a surprisingly high 2-year disease-free survival (DFS) in high-risk diffuse large B-cell lymphoma (DLBCL), a prospective nonrandomized trial showed.

Patients who were in complete remission after and then received the PD-L1 inhibitor for up to a year had a 2-year DFS of 87.9%, almost 10 percentage points higher than with chemotherapy alone. The 109-patient cohort had a 2-year overall survival (OS) of 96.3%.

Among patients who relapsed and received additional chemotherapy, 10 of 13 had complete responses, showing that chemosensitivity is restored after checkpoint inhibition, reported Marcel Nijland, MD, of the University of Groningen in the Netherlands, at the European Hematology Association meeting in Madrid.

"Atezolizumab consolidation in this high-risk population led to a disease-free survival of 88%, meeting the primary endpoint of the study," said Nijland. "The excellent overall survival also was a little bit of a surprise to us, but what we observed is that these patients become chemosensitive again. The main toxicities were infectious complications, and I think the adverse effects that we observed in terms of immune phenomena were in line with expectations."

"So we believe that consolidation with checkpoint inhibitors might be a potential strategy in patients with diffuse large B-cell lymphoma," he added.

Whether the encouraging results move forward in additional trials depends on whether drug manufacturer Roche/Genentech is swayed by the results.

"We addressed this question with Roche, but for now, the answer is no, since they have no interest in this indication for atezolizumab," said Nijland. "Of course, this is food for thought."

"I think the majority of us would have said checkpoint inhibitors in DLBCL, well, that's a lost cause," he added. "I think these data should make us think about how we apply this strategy."

An unidentified speaker in the audience asked about the decision to give atezolizumab as consolidation therapy instead of simultaneous or combined regimens.

"The idea was if you give a treatment with T cell-toxic cyclophosphamide, you are probably dampening the immune response," said Nijland. "Because of that, the idea was not to give [atezolizumab] simultaneously."

In response to another question, he said investigators followed the lead established for solid malignancies and chose to continue consolidation for a maximum of 12 months.

"We were much more strict as to the stopping rules since this was a phase II trial of patients with no active disease," said Nijland. "So with any suspicion of immune phenomena, patients should stop."

R-CHOP for high-risk DLBCL leads to a 5-year progression-free survival (PFS) of 60%, but a fourth of patients relapse after achieving a complete response. or adding (Polivy) to R-CHP improves PFS but not OS, Nijland noted.

About 30% of DLBCL expresses PD-L1, which is related to outcome, he continued. However, experience with PD-1/L1 inhibitors in relapsed/refractory DLBCL has been .

"When we started this study, there were signs that checkpoint inhibitors as maintenance after autologous stem cell transplantation in patients with complete remission ," said Nijland. "We hypothesized that patients with high-risk diffuse large B-cell lymphoma -- defined as an of 3, 4, or 5 -- if we use the R-CHOP regimen for debulking, we know that a quarter of these patients will relapse, even if their PET scan is negative at the end of treatment."

"We thought of a consolidation strategy similar to studies performed in solid malignancies," he continued. "In this case, we opted for a monoclonal antibody directed at PD-L1. The aim of the study was to improve 2-year disease-free survival in patients with high-risk DLBCL in complete remission with a 1-year consolidation with atezolizumab."

The trial had statistical power to detect an improvement in 2-year DFS from 78% to ≥86%. OS and toxicity were principal secondary endpoints.

The study population had a median age of 64, and men accounted for about 60% of the total. Two-thirds of the patients had an IPI score of 3, and 95% had attained complete remission after six cycles of R-CHOP (the rest after eight cycles). All but four of 55 evaluable patients tested negative for PD-L1 expression in lymphoma, but 46 of 56 patients had PD-L1 expression in the tumor microenvironment.

Two-thirds of patients received all treatment, whereas 17% discontinued because of adverse events, slightly higher than the 10-15% frequency with adjuvant immune checkpoint inhibition for solid tumors, said Nijland.

The study population had a median follow-up 36.4 months and met the primary endpoint 2-year DFS, exceeding the 86% threshold. The 2-year OS was one of the highest reported to date.

The trial was conducted during the COVID pandemic, and COVID accounted for half of all infections (25% overall incidence). Lab abnormalities and musculoskeletal issues occurred in 10-15% of patients. All other adverse events (AEs) occurred in fewer than 10% of patients. Grade 3 AEs occurred in 20.6% of patients (primarily infections and lab abnormalities), grade 4 in 2.7%, and grade 5 in 1.6%.

Immune-related (ir) AEs occurred in 18.3% of patients, with endocrinopathies accounting for half. The incidence of grade 3-4 irAEs was 4.5%.

Comment