PD-1 Inhibitors Demonstrate Promise as Salvage Therapy in R/R Extranodal NK/T-cell Lymphoma

According to a comparative analysis conducted based on propensity score matching, anti–PD-1 therapy with either pembrolizumab (Keytruda) or nivolumab (Opdivo) significantly improved overall survival (OS) compared with historical salvage therapy in patients with relapsed/refractory extranodal natural killer/T-cell lymphoma (ENKTCL).

Data presented at the 2023 EHA Congress by Amira Marouf, MD, PhD student, showed that the improved survival of patients who experienced on-treatment relapse following anti–PD-1 therapy may have been a result of subsequent salvage treatments including immunotherapy continuation.

“The findings confirm that anti­–PD-1 therapy is the best [and most] promising approach for patients with relapsed/refractory disease. The future [will likely] include anti–PD-1 therapy as frontline therapy for these patients to improve their prognosis,” Marouf said. “We have to find the best association from this immunotherapy to chemotherapy as frontline therapy to select the best patients and improve the understanding of predictive factors of response to immunotherapy.”

At a median follow-up of 6.5 months (range, 1.0-62.4), a combined population of patients with relapsed/refractory ENKTCL, including a prospective cohort (n = 12) and a real-life French cohort (n = 25), experienced an overall response rate of 40.5% with a complete response rate of 35% following treatment with pembrolizumab or nivolumab after receiving L-asparaginase as frontline therapy and at least 1 cycle of anti–PD-1 salvage therapy. Additionally, the median OS was not yet reached, and the 2-year OS rate was 50.2%.

After propensity score matching, a comparative analysis of the combined population vs a national observatory group (n = 38) demonstrated that patients treated with an anti-PD-1 agents as salvage therapy experienced a significant OS benefit (P = .011).

In an interview with OncLive^®, Marouf, medical faculty at Necker Hospital/Imagine Institute at the Université Paris Cité in France, described the nature of the analysis and discussed the main takeaways regarding the efficacy of PD-1 inhibitors for patients with relapsed/refractory ENKTCL.

OncLive: What was the rationale behind this research?

Marouf: ENKTCL is a very rare subset of peripheral T-[cell] lymphoma, which is an aggressive disease with poor outcomes for the patient, especially for those who experience relapsed/refractory disease. Recent studies highlighted that immune escape mechanisms are involved in the pathogenesis of the disease and especially PD-L1 upregulation. That’s why we examined the efficacy of anti–PD-1 therapy in these patients in a French cohort group. Also, all the studies published in this field were not comparative. To date, there were not any comparative analyses. That’s why we performed a matched cohort [analysis] based on propensity scores, and we highlighted that anti–PD-1 therapy has much more efficacy compared with previous salvage therapy.

What were the criteria for selecting patients?

We selected a cohort of 37 patients treated with asparaginase[-containing regimens] as frontline therapy, which is a standard of care in this disease. We included [those with] both localized and disseminated stage [disease], and from these 37 patients, 12 were prospectively included in the ACSE Unicancer protocol, and the others were from the real-life data. We firstly compared those 2 [types of] patients, and we observed comparable results from the real-life data and the protocol analysis. Then, we made them 1 cohort and compared it with a historical cohort. Patients in the historical cohort [had] the same criteria and were [treated] before the immunotherapy era.

What were the key findings from this analysis presented at the 2023 EHA Congress?

The main result is that after propensity score matching, we observed that patients from the anti–PD-1 group had improved OS. [However], we were not able to show improved PFS. There are many hypotheses for [this contrast]. Maybe the improved OS of patients is based on subsequent salvage therapy. [Most likely], the association of chemotherapy to immunotherapy is the best proposal [for improved OS] for these patients.

What is the take-home message for clinicians regarding this research?

The take-home message is to not stop immunotherapy early after what we consider a relapse because we need some time to evaluate the efficacy of immunotherapy in these patients.

Reference

Marouf A. Efficacy of anti-PD1 therapy in relapsed or refractory extranodal NK/T cell lymphoma: a matched cohort analysis from the LYSA. Hematol Oncol. 2023;41(S2):503-503. doi:10.1002/hon.3164_369