Anakinra versus etoposide‐based therapy added to high‐dose steroids for the treatment of secondary hemophagocytic lymphohistiocytosis

Abstract

Objective Hemophagocytic lymphohistiocytosis (HLH) is a rare life‐threatening, hyperinflammatory syndrome usually treated with high‐dose steroids (HDS), often complemented with adjunct therapies, such as etoposide (HLH‐94 protocol). Anakinra has been reported to effectively treat HLH; however, has not been comparatively examined with etoposide‐based therapies. We sought to evaluate the effectiveness and durability of these treatment approaches. Methods We performed a retrospective analysis of all adult patients diagnosed with secondary HLH between January 2011 and November 2022 who received anakinra and HDS, the HLH‐94 protocol, HDS alone, or supportive care. Results Thirty adult patients with secondary HLH were included. Cumulative incidence (CI) of response at 30 days was 83.3%, 60%, and 36.4% for patients treated with anakinra, the HLH‐94 protocol, and HDS alone, respectively. CI of relapse at 1 year was 50%, 33.3%, and 0% with the HLH‐94 protocol, HDS, and anakinra and HDS, respectively. Overall survival at 1 year was higher with anakinra and HDS compared to the HLH‐94 protocol, yet was not statistically significant (77.8% vs. 33.3%; hazard ratio: 0.29; p = .25). Conclusion Treatment with anakinra and HDS in adults with secondary HLH was associated with higher response rates with longer survival compared with alternative therapies and should be further investigated in this setting.

Improved survival outcomes with anakinra over etoposide-based therapies for the management of adults with hemophagocytic lymphohistiocytosis: a retrospective multicenter research network study

“… 14 In adult patients receiving the HLH-94 protocol, 1-year OS rates are dismal ranging between 29% and 35%. 2 , 15 , 16 In addition, the high cumulative exposure to etoposide from the HLH-94 protocol has been implicated in significantly increasing the risk of secondary hematologic malignancy.…”

“…Recent findings of anakinra use for HLH management have suggested therapeutic benefit in adult patients. 2 – 5 Collectively, treatment response from a pooled analysis of four studies was 78.3% ( n = 36/46) with 1-year OS reported as 33.3% ( n = 9) and 77.8% ( n = 6) from two studies. 2 – 5 With a median follow-up of 10 months, Bavarez et al also reported an OS of 88.2% in their subset of adult patients ( n = 18) who received anakinra (one patient with prior etoposide treatment was excluded).…”

“… 2 – 5 Collectively, treatment response from a pooled analysis of four studies was 78.3% ( n = 36/46) with 1-year OS reported as 33.3% ( n = 9) and 77.8% ( n = 6) from two studies. 2 – 5 With a median follow-up of 10 months, Bavarez et al also reported an OS of 88.2% in their subset of adult patients ( n = 18) who received anakinra (one patient with prior etoposide treatment was excluded). 3 These findings were similar to our analysis in which 1-year OS was 79.3% in the unmatched cohort.…”

“…Recent reports have described positive outcomes with the utilization of ruxolitinib or anakinra although these publications are limited to case reports and small studies. 2 – 12 Herein, we aim to compare survival outcomes of adult patients with HLH who were treated with ruxolitinib, anakinra, and etoposide-based therapies.…”

Immune Effector Cell-Associated HLH-like Syndrome: A Review of the Literature of an Increasingly Recognized Entity

“…While this agent was approved for the treatment of rheumatologic disorders, promising data from off-label use in adults and children have brought it forward into the recommended treatment options in HLH/MAS per the consensus of the Histiocyte Society [55]. Retrospective studies using anakinra in secondary HLH are very encouraging with overall response rates as high as 80-90% [56,57]. In addition, case series have alluded to its efficacy in IEC-HS in patients treated with CD19 CAR-T products for pediatric B-ALL, DLBCL and mantle cell lymphoma [58,59].…”