Nivolumab Shows Modest Clinical Activity, But Some Hyperprogression Observed in Patients with R/R PTCL

Single-agent nivolumab was associated with modest activity in patients with relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL); however, the treatment was associated with a short duration of response (DOR) and multiple cases of hyperprogression, according to the results of an investigator-initiated phase II, prospective study.

Despite results indicating modest clinical activity by nivolumab, a program death receptor 1 immune checkpoint inhibitor, in patients with R/R PTCL, a decision was made to halt the phase II study due to the high number of cases of hyperprogression and the short DOR.

The interim analysis included 12 patients who received at least one cycle of nivolumab. Half (n=6) of patients had angioimmunoblastic T-cell lymphoma (AITL), and three had PTCL. Most (n=11) had advanced stage and extranodal disease (97.1%) and had received a prior autologous stem cell transplant (50%).

The primary objective of the study was to assess the overall response rate (ORR). Secondary objectives were to assess safety and tolerability of nivolumab in PTCL and to assess progression-free survival (PFS), DOR, and overall survival (OS).

The ORR was 33% (95% CI, 12.3-63.7), with two cases each of complete response and partial response. The median PFS was short at 2.7 months (95% CI, 1.5 to not estimable [NE]), and the median OS was 6.7 months (95% CI, 3.4 to NE). The median DOR was also short at 3.6 months (95% CI, 1.9 to NE).

Hyperprogressive disease, defined as time-to-treatment failure of less than or equal to one month from initiation of therapy, occurred in four patients, three of whom had AITL.

Grade ≥3 non-hematologic adverse events occurred in 42% of patients, and hematologic adverse events occurred in 25%.

“These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases,” concluded the authors, led by N. Nora Bennani, MD, of the Division of Hematology at the Mayo Clinic in Rochester, Minnesota.

Bennani NN, Kim HJ, Pederson LD, et al. Nivolumab in patients with relapsed or refractory peripheral T-cell lymphoma: modest activity and cases of hyperprogression. J Immunother Cancer. 2022;10(6):e004984. doi:10.1136/jitc-2022-004984