Background: Salvage chemotherapy (CHT) followed by autologous stem cell transplant (ASCT) is considered the standard of care for classical Hodgkin lymphoma (cHL) patients who are primary refractory (PrRef) to first line treatment. However, among the few studies based solely on PrRef cHL cases, it has been reported that this strategy leads to a sustained complete response (CR) in almost a half of PrRef patients (pts). Furthermore, Horning et al. reported an overall survival (OS) of 50% at a median follow up of 42 months in a cohort of 29 PrRef pts. Although it is conventionally believed that chemorefractory pts are poor ASCT candidates, recent studies reported promising results in terms of response rate and survival among PrRef cases receiving anti-PD-1 salvage treatment and subsequent ASCT.
Methods: We retrospectively collected 9 consecutive PrRef cHL pts who did not respond to salvage CHT and brentuximab-vedotin (BV) and were treated with pembrolizumab monotherapy as fourth-line. Pts defined as PrRef were those who did not achieve a durable (>90 days) CR at the end of first line therapy or those with a Deauville score of 5 (DS 5) at interim PET (PET-2).
Results: The majority of pts were male (67%). Systemic symptoms were reported in 56% of cases. Stage at the onset was 2 in 5 cases and 3 and 4 in 2 pts each. An unfavourable prognostic score was seen in 75% of pts. Nodular sclerosis was the predominant histological variant (67%); LMP-1 was positive in 2 out of 7 evaluable cases. The median number of cycles of pembrolizumab administered was 6 (range, 2 to 9). After anti-PD-1 therapy, 75% pts obtained a CR and 25% a partial response (PR). Seven pts underwent ASCT subsequently to pembrolizumab: among these, 87% pts achieved a metabolic CR and 14% a PR at the pre-ASCT PET scan. Disease evaluation after ASCT showed a CR in 100% of cases. After a median follow-up time of 40.3 months (interquartile range: 20.4-54.7 months) from first-line treatment failure, all pts still maintain a CR.
Conclusion: If compared to similar series of PrRef cases reported in literature, our experience using pembrolizumab before ASCT resulted in successful outcomes in terms of quality and duration of response in this difficult-to-treat subset of cHL pts.