Outcomes and Toxicities of Programmed Death-1 (PD-1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Real-World, Multicenter Retrospective Analysis

Abstract

Background Although classical Hodgkin lymphoma (cHL) is highly curable, 20%–30% of patients will not be cured with conventional treatments. The programmed death‐1 (PD‐1) inhibitors (PD‐1i) nivolumab and pembrolizumab have been Food and Drug Administration‐approved for relapsed/refractory (R/R) cHL. There is limited data on the real‐world experience with PD‐1i in cHL and it is unknown whether fewer selected patients treated with PD‐1i derive benefits similar to those observed in published trials. Materials and Methods We performed a multicenter, retrospective analysis of R/R cHL patients treated with PD‐1i in the nontrial setting. The primary objective was to describe progression‐free survival (PFS) and overall survival (OS) in this population. Secondary objectives were to characterize response rates, toxicities, discontinuation patterns, and post‐PD‐1i therapies. Results The study included 53 patients from nine U.S. centers. Overall response rate (ORR), complete response (CR), and partial response (PR) to PD‐1i were 68%, 45%, and 23%, respectively. Twelve‐month OS and PFS were 89% and 75%, respectively; median PFS was 29 months. Ninety‐six percent of patients with CR continue to respond at a median follow‐up of 20 months. Toxicities were similar to those previously described. Seventy percent of patients treated with systemic therapy after PD‐1i demonstrated objective responses. Conclusion To our knowledge, this analysis is the first describing real‐world experience with PD‐1i in cHL patients in the U.S. Here, we demonstrate similar response rates compared to prior studies. The toxicity profile of PD‐1i was similar to that seen in previous studies; we further describe toxicity patterns in those with prior autoimmune disease or allogeneic transplant. Post‐PD‐1i systemic therapies appear active. These results support the effectiveness and tolerability of PD‐1i therapy in R/R cHL in a real‐world setting. Implications for Practice Two PD‐1 inhibitors have recently been approved for patients with relapsed/refractory classical Hodgkin lymphoma based on results from nonrandomized clinical trials. However, to date, there have been no studies evaluating the effectiveness and toxicity profile of these drugs in the real‐world setting in the U.S. The present study demonstrates that patients treated in a real‐world context experience similar rates of overall effectiveness compared with published clinical trials. Patients who discontinue PD‐1 inhibitors may experience clinical responses to subsequent treatment with systemic chemotherapy or targeted therapy. This study provides clinicians with further insight into the effectiveness and tolerability of PD‐1 inhibitors and suggests that when patients progress while on these drugs, conventional systemic chemotherapy may be an effective treatment option.

Checkpoint inhibitors in AML: are we there yet?

“…The spectrum of irAEs is diverse and can involve almost any tissue or organ (Bair et al , ). These events include but are not limited to complications in skin (rash, vitiligo, toxic epidermal necrolysis) (Abdel‐Rahman et al , ), the lungs (pneumonitis, pleural effusion) (Naidoo et al , ), thyroid gland (hypothyroidism) (Ryder et al , ), the gastrointestinal tract (colitis, pancreatitis, celiac disease) (Beck et al , ; Peyrony et al , ), the nervous system (encephalopathy, Guillain‐Barré syndrome, myelitis) (Liao et al , ), the liver (hepatitis) (Lleo et al , ), the heart (myocarditis) (Quagliariello et al , ) and hematological cells (immune cytopenias) (Friedman et al , ).…”

Real-World Healthcare Resource Utilization in Patients with Classical Hodgkin Lymphoma Treated with Pembrolizumab and Nivolumab in the USA

“…However, the standard of care data was based on a study conducted prior to the FDA approval of nivolumab, and while 28 of 79 included patients were treated with investigational agents, the proportion receiving nivolumab was not disclosed [ 10 ]. With regard to the real-world outcomes of PD-1 inhibitors as a whole, a retrospective analysis of patients with relapsed or refractory cHL treated with a PD-1 inhibitor in US clinical practice was conducted by Bair et al, which identified 52 patients treated with nivolumab and one patient treated with pembrolizumab [ 32 ]. While a comparison between the two PD-1 inhibitors was not possible, the study identified an ORR of 68% for all patients, which is similar to the ORRs reported in the pivotal pembrolizumab and nivolumab clinical trials.…”

Evolving Use of Real-World Evidence in the Regulatory Process: a Focus on Immuno-Oncology Treatment and Outcomes

“…Over the past few years, there have been multiple examples of RWD sources rapidly providing valuable data on the impact of newly licensed I-O therapies, particularly in the context of assessing the generalizability of effectiveness and/or tolerability to broad patient populations [48][49][50][51][52][53], or specific populations usually excluded from clinical trials [50,54,55]. These postapproval data extend our overall understanding of the efficacy and safety profiles of new I-O therapies.…”