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Multicenter Study
. 2024 May 14;8(9):2248-2258.
doi: 10.1182/bloodadvances.2023012217.

Real-world treatment patterns and outcomes in patients with primary hemophagocytic lymphohistiocytosis treated with emapalumab

Shanmuganathan Chandrakasan  1 , Michael B Jordan  2   3 , Ashley Baker  4 , Edward M Behrens  5 , Deepika Bhatla  6 , May Chien  7 , Olive S Eckstein  8 , Michael M Henry  9 , Michelle L Hermiston  10 , Ashley P Hinson  11 , Jennifer W Leiding  12 , Abiola Oladapo  13 , Sachit A Patel  14 , Priti Pednekar  15 , Anish K Ray  16 , Blachy Dávila Saldaña  17 , Susmita N Sarangi  18 , Kelly J Walkovich  19 , John D Yee  13 , Adi Zoref-Lorenz  2   20 , Carl E Allen  8
Affiliations
Multicenter Study

Real-world treatment patterns and outcomes in patients with primary hemophagocytic lymphohistiocytosis treated with emapalumab

Shanmuganathan Chandrakasan et al. Blood Adv. .

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, hyperinflammatory syndrome. Emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon gamma, is approved in the United States to treat primary HLH (pHLH) in patients with refractory, recurrent, or progressive disease, or intolerance with conventional HLH treatments. REAL-HLH, a retrospective study, conducted across 33 US hospitals, evaluated real-world treatment patterns and outcomes in patients treated with ≥1 dose of emapalumab between 20 November 2018 and 31 October 2021. In total, 46 patients met the pHLH classification criteria. Median age at diagnosis was 1.0 year (range, 0.3-21.0). Emapalumab was initiated for treating refractory (19/46), recurrent (14/46), or progressive (7/46) pHLH. At initiation, 15 of 46 patients were in the intensive care unit, and 35 of 46 had received prior HLH-related therapies. Emapalumab treatment resulted in normalization of key laboratory parameters, including chemokine ligand 9 (24/33, 72.7%), ferritin (20/45, 44.4%), fibrinogen (37/38, 97.4%), platelets (39/46, 84.8%), and absolute neutrophil count (40/45, 88.9%). Forty-two (91.3%) patients were considered eligible for transplant. Pretransplant survival was 38 of 42 (90.5%). Thirty-one (73.8%) transplant-eligible patients proceeded to transplant, and 23 of 31 (74.2%) of those who received transplant were alive at the end of the follow-up period. Twelve-month survival probability from emapalumab initiation for the entire cohort (N = 46) was 73.1%. There were no discontinuations because of adverse events. In conclusion, results from the REAL-HLH study, which describes treatment patterns, effectiveness, and outcomes in patients with pHLH treated with emapalumab in real-world settings, are consistent with the emapalumab pivotal phase 2/3 pHLH trial.

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Conflict of interest statement

Conflict-of-interest disclosure: C.E.A. reports advisory board membership with Sobi Inc and Opna, and research support from Genentech and Opna. M.M.H. serves on a speaker/advisory board for Sobi Inc and is a speaker for ClearPoint. M.B.J. reports advisory board membership with Sobi Inc and received research support from Sobi Inc and Bristol Myers Squibb. J.W.L. serves on a speaker/advisory board for Sobi Inc; serves on the advisory board of Horizon; is an employee of bluebird bio; and holds stock in bluebird bio. A.O. is an employee of Sobi Inc and holds stock in Sobi Inc. P.P. is an employee of PRECISIONheor and served as consultant for Sobi Inc at the time of study. S.A.P. serves on a speaker/advisory board for Sobi Inc. A.K.R. is a speaker for BTC International Inc and Sobi Inc. J.D.Y. was an employee, at time of study, of Sobi Inc. A.Z.-L. serves as consultant for Sobi Inc. The remaining authors declare no competing financial interests.

A complete list of the members of the REAL-HLH Investigators appears in “Appendix.”

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Patient disposition.
Figure 2.
Figure 2.
Emapalumab dosing. (A) Timing of emapalumab treatment initiation from HLH diagnosis. (B) Duration of emapalumab treatment. (C) Median (range) emapalumab dosing. (D) Number of emapalumab doses.
Figure 3.
Figure 3.
Normalization of laboratory parameters in response to treatment with emapalumab. (A) Time to first normalization of laboratory parameters from emapalumab initiation to the end of study period. (B) Proportion of patients exhibiting normalization of laboratory parameters.
Figure 4.
Figure 4.
Emapalumab treatment and HSCT.
Figure 5.
Figure 5.
Survival in patients treated with emapalumab. (A) Overall survival from emapalumab initiation to the end of study period. (B) Relationship between the emapalumab treatment parameters and survival.
See this image and copyright information in PMC

References

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