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.

in Blood cancer journal by Timothy J Voorhees, Eric M McLaughlin, Pallawi Torka, Jorge Florindez, Na Hyun Kim, Tamara K Moyo, Heather Reves, Nuttavut Sumransub, Saarang Deshpande, Ashley Rose, Cassandra Duarte, Muhammad Salman Faisal, Showkat Hamid, Suki Subbiah, Sabarish Ayyappan, Lauren Shea, Matt Cortese, Krish Patel, Ajay Major, Hayder Saeed, Jakub Svoboda, Sanjal Desai, Praveen Ramakrishnan Geethakumari, Mehdi Hamadani, Natalie Grover, Narendranath Epperla

TLDR

  • The study assessed outcomes in patients with double refractory/intolerant classic Hodgkin lymphoma who had failed brentuximab vedotin and anti-PD-1 therapies.
  • Results showed that patients who had undergone autologous stem cell transplant before developing double refractory/intolerant cHL had improved overall survival, and rechallenge with anti-PD-1 or BV-based therapies was effective.
  • Advanced therapy options were associated with improved overall survival, providing new opportunities for treatment in this patient population.

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.

Overview

  • The study evaluated outcomes in patients with double refractory/intolerant classic Hodgkin lymphoma (cHL) who had failed brentuximab vedotin (BV) and anti-PD-1 therapies.
  • A total of 173 patients were identified with double refractory/intolerant cHL from 15 US academic medical centers.
  • The study aimed to assess the clinical outcomes and identify potential therapeutic options for patients with double refractory/intolerant cHL.

Comparative Analysis & Findings

  • Patients who had undergone autologous stem cell transplant prior to developing double refractory/intolerant cHL had significantly longer overall survival from time of cHL diagnosis (OS-1) compared to those who had not.
  • Rechallenge with anti-PD-1 or BV-based therapies was effective, with median progression-free survival (PFS) ranging from 155 to 357 days.
  • Advanced therapy options such as CD30-directed chimeric antigen receptor T-cell therapy and allogeneic stem cell transplant after double refractory/intolerant cHL were associated with improved overall survival.

Implications and Future Directions

  • The study highlights the importance of evaluating outcomes in patients with double refractory/intolerant cHL, who have limited treatment options.
  • Further research is needed to identify more effective therapies for patients with double refractory/intolerant cHL, particularly in terms of improving overall survival.
  • The use of advanced therapy options, such as CD30-directed chimeric antigen receptor T-cell therapy and allogeneic stem cell transplant, may provide new opportunities for treatment in this patient population.
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