The median overall survival (OS) of patients with classic Hodgkin lymphoma (cHL) whose disease had progressed after an autologous hematopoietic cell transplant (AHCT) and who were treated since brentuximab vedotin (BV) and anti-PD-1 immune checkpoint inhibitors have been available for patients was 9.5 years. The results of the retrospective study were published in Blood Advances. This longer OS is an improvement since these agents were approved by the U.S. Food and Drug Administration to treat patients with newly diagnosed cHL. Before 2010, the median OS of patients whose disease relapsed post-AHCT was two to three years.
“Patients who were treated with checkpoint inhibitors first had significantly better OS compared to patients who were treated with chemotherapy or radiation first. Patients who were treated with BV first had similar OS to patients who received chemotherapy or radiation first,” said study author Sanjal H. Desai MD, assistant professor of medicine at the University of Minnesota in Minneapolis.
An AHCT is standard for patients with relapsed or refractory cHL, and 40% to 50% progress after receiving one. According to Dr. Desai, patients who progress after an AHCT were conventionally treated with chemotherapeutic agents and radiation, and some received an allogeneic hematopoietic cell transplant (alloHCT). In the last 10 years, BV and anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab have shown encouraging response and progression-free survival in clinical trials of patients who progress after AHCT.
Checkpoint inhibitors and BV are used after post-AHCT relapses, but larger studies to understand outcomes with these agents have been missing.
Dr. Desai and her colleagues conducted a large observational cohort study to assess the effect of these newer therapies on patient outcomes, as well as to assess prognostic factors and the impact of therapy sequencing on those patients whose cHL progressed after transplant.
The team analyzed 367 patients with cHL in the U.S. and the Czech Republic who relapsed after AHCT. The median age of patients was 34 years (range = 27-46), and 52% were male. The median time to progression after transplant was six months, and 336 patients had at least one pre-AHCT modified ATHERA risk factor.
The median patient follow-up was 48.1 months, and the 10-year post-progression overall survival (PPS) was 46.2% (95% CI 35.3-60.3). There was no significant difference between the PPS of the U.S. and the Czech Republic.
Receipt of an AHCT was not associated with better OS. Patients who were older than 40 years, patients who relapsed within six months of AHCT, and patients who received an AHCT in partial response had worse OS in the novel agent era, with a median OS of about 60 months.
About 73% of patients received the newer agents after progression post-AHCT. “Patients who received nivolumab or pembrolizumab first following an AHCT had better OS, which underscores the importance of employing checkpoint inhibitors, specifically nivolumab and pembrolizumab, earlier in the course of treatment for patients who progress after an AHCT,” noted Dr. Desai. “It was also surprising to see that alloHCT was not associated with definitive OS benefit. This underscores the fact that alloHCT might not be a preferred strategy for all patients who progress after AHCT, and careful patient selection is important.”
According to Dr. Desai, further studies are needed to better characterize patient populations that can benefit from alloHCT. Additionally, because patients with cHL who progress after AHCT have encouraging OS since the availability of newer agents, studies to evaluate outcomes of patients who are refractory to or relapse subsequent to treatment with these newer agents are needed to design optimal clinical trials for this subpopulation of patients.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Desai SH, Spinner MA, Evens AM, et al. Overall survival of cHL patients who progress after autologous stem cell transplant: results in novel agent era [published online ahead of print, 2023 Sep 20]. Blood Advances. doi: bloodadvances.2023011205.
