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Multicenter Study
. 2025 Mar 26;15(1):45.
doi: 10.1038/s41408-025-01257-1.

Outcomes in patients with classic Hodgkin lymphoma refractory or intolerant to brentuximab vedotin and anti-PD-1 therapy: a real world analysis from 15 U.S. academic centers

Timothy J Voorhees  1 , Eric M McLaughlin  2 , Pallawi Torka  3 , Jorge Florindez  4 , Na Hyun Kim  5 , Tamara K Moyo  6 , Heather Reves  7 , Nuttavut Sumransub  8 , Saarang Deshpande  9 , Ashley Rose  10 , Cassandra Duarte  11 , Muhammad Salman Faisal  12 , Showkat Hamid  12 , Suki Subbiah  13 , Sabarish Ayyappan  14 , Lauren Shea  15 , Matt Cortese  12 , Krish Patel  16 , Ajay Major  11 , Hayder Saeed  10 , Jakub Svoboda  9 , Sanjal Desai  8 , Praveen Ramakrishnan Geethakumari  7 , Mehdi Hamadani  5 , Natalie Grover  4 , Narendranath Epperla  17   18
Affiliations
Multicenter Study

Outcomes in patients with classic Hodgkin lymphoma refractory or intolerant to brentuximab vedotin and anti-PD-1 therapy: a real world analysis from 15 U.S. academic centers

Timothy J Voorhees et al. Blood Cancer J. .

Abstract

Anti-PD-1 based therapies and brentuximab vedotin (BV) have significantly improved survival in patients with classic Hodgkin lymphoma (cHL) and have been incorporated into earlier lines of therapy. However, there is insufficient data regarding the clinical outcomes in patients who develop refractory disease or who become intolerant of BV and anti-PD-1 therapies (double refractory/intolerant; DR/INT). Here, we evaluated outcomes in patients with DR/INT cHL from 15 US academic medical centers. A total of 173 patients were identified as DR/INT. The median overall survival from the time of cHL diagnosis (OS-1) was 14.8 years (95% CI: 10.9-20.9 years) and the 10-year OS-1 estimate was 62% (95% CI: 52-70%). After accounting for differences in age, patients who underwent autologous stem cell transplant prior to developing DR/INT had significantly longer OS-1 (HR 0.53, 95% CI: 0.29-0.96, p = 0.04). Median OS from time of DR/INT (OS-2) was 7.4 years (95% CI: 4.3-NR) and the 5-year OS-2 estimate was 57% (95% CI: 48-66%). Both anti-PD-1 and BV based therapy rechallenge were effective with median PFS of 237 days (95% CI: 155-357 days) and 183 days (95% CI: 108-273 days), respectively. Finally, advanced therapy options such as CD30 directed chimeric antigen receptor T-cell therapy and allogeneic stem cell transplant after DR/INT were associated with improved OS-2 (p < 0.001). To our knowledge, this represents the largest cohort of patients with DR/INT cHL. OS-2 will serve as a benchmark for future studies aiming to improve survival in DR/INT cHL.

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Conflict of interest statement

Competing interests: NE: Research funding: Beigene, Lilly, and Incyte; Speakers Bureau for Beigene and Genentech, Ad boards for ADC Therapeutics, Lilly, and Ipsen; Honorarium from Novartis. TJV: Advisory Board: Genmab/AbbVie, ADC Therapeutics. Consultancy: Novartis, Recordati, Genmab. Research Funding: Kite, Viracta, Incyte/Morphosys, Genmab/AbbVie, Recordati. TKM: Advisory Board: Kite. Research funding: Genmab, Century Therapeutics, Johnson & Johnson. PRG: Consultancy: Kite/Gilead Pharma, Bristol Myers Squibb (BMS). Advisory Board ADC Therapeutics, Bristol Myers Squibb (BMS), Cellectar Biosciences, Ono Pharma, Ipsen Biopharma and Regeneron Pharma. SS: Advisory Board ADC Therapeutics. CD: Advisory Board: EMD Serono Advisory Board, Cogent Biosciences. Ethics approval: This retrospective study approved through The Ohio State University institutional review board (Study Number: 2022C0159). Given the retrospective nature of this study, individual patient consent was waived and de-identified data was utilized for analysis. The study was conducted in accordance with relevant guidelines and regulations.

Figures

Fig. 1
Fig. 1. Overall survival from diagnosis (OS-1).
A the full cohort, (B) cohort stratified by INT (red) or DR (blue), (C) cohort stratified by prior ASCT (red) or no prior ASCT (blue) at the time of DR/INT.
Fig. 2
Fig. 2. Overall survival from the time of DR/INT (OS-2).
A the full cohort, (B) cohort stratified by INT (red) or DR (blue). C Progression free survival (PFS) for patients rechallenged with anti-PD-1 based therapy (red) or BV based therapy (blue).
Fig. 3
Fig. 3
Overall survival from the time of DR/INT (OS-2) stratified by subsequent AlloSCT (blue), CD30.CAR-T cell therapy (red), or neither therapy (green).
See this image and copyright information in PMC

References

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