SAN DIEGO—Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.

Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.

“It’s very promising . . . to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president and head of medical at Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.

Dr. Eid also noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.

These results were presented as a poster at the 2018 ASH Annual Meeting (abstract 1691).

Rationale

Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.

“The initial therapy works well in 70% to 80% of patients, but the patients who fail don’t have good options,” he said.

Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.

Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.

Patients and treatment

The interim analysis of this trial included 30 patients with relapsed/refractory PMCBL. Their median age at enrollment was 35.5 (range, 19 to 83), and 57% of patients were female.

Sixty percent of patients had refractory disease, 23% had relapsed disease, and 17% had both.

The median number of prior therapies was 2 (range, 1-5). Thirteen percent of patients had prior autologous stem cell transplant.

The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.

At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit (n=9), disease progression (n=7), AEs unrelated to treatment (n=2), patient request (n=1), and “other” reasons (n=1).

Safety

“There were no new safety signals,” Dr. Eid said. “The adverse events reflected the two agents’ profiles.”

The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).

Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).

The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.

The acute kidney injury was the only fatal AE considered treatment-related. There were three other deaths in the trial, but they were considered unrelated to treatment.

Response

The complete response rate was 27% (n=8), and the partial response rate was 43% (n=13), for an overall response rate of 70% (n=21).

“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.

Ten percent of patients (n=3) had stable disease, 13% (n=4) progressed, and investigators were unable to determine the status for 7% of patients (n=2).

The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.

Overall and progression-free survival data are not yet mature.

Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.

“The results are very, very promising,” Dr. Eid said.

This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics.

Two-drug combo deemed ‘very promising’ for PMBCL