INDICATIONS
Gamifant (emapalumab-lzsg) is an interferon gamma (IFNγ)-neutralizing antibody indicated for the treatment of adult and pediatric (newborn and older) patients with:
- Primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance with conventional HLH therapy.
- HLH/macrophage activation syndrome (MAS) in known or suspected Still’s disease, including systemic Juvenile Idiopathic Arthritis (sJIA), with an inadequate response or intolerance to glucocorticoids, or with recurrent MAS.
IMPORTANT SAFETY INFORMATION
Infections
Gamifant may increase the risk of fatal and serious infections with pathogens including mycobacteria, herpes zoster virus... and histoplasma capsulatum. Do not administer Gamifant in patients with these infections until appropriate treatment has been initiated.
INDICATIONS
Gamifant (emapalumab-lzsg) is an interferon gamma (IFNγ)-neutralizing antibody indicated for the treatment of adult and pediatric (newborn and older) patients with:
- Primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance with conventional HLH therapy.
- HLH/macrophage activation syndrome (MAS) in known or suspected Still’s disease, including systemic Juvenile Idiopathic Arthritis (sJIA), with an inadequate response or intolerance to glucocorticoids, or with recurrent MAS.
IMPORTANT SAFETY INFORMATION
Infections
Gamifant may increase the risk of fatal and serious infections with pathogens including mycobacteria, herpes zoster virus, and histoplasma capsulatum. Do not administer Gamifant in patients with these infections until appropriate treatment has been initiated.
In patients with primary HLH receiving Gamifant in clinical trials, serious infections such as sepsis, pneumonia, bacteremia, disseminated histoplasmosis, necrotizing fasciitis, viral infections, and perforated appendicitis were observed in 32% of patients.
In patients with HLH/MAS in Still’s disease receiving Gamifant in clinical trials, serious infections such as pneumonia, cytomegalovirus infection, cytomegalovirus infection reactivation, and sepsis were observed in 13% of patients.
Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating Gamifant. Administer tuberculosis prophylaxis to patients at risk for tuberculosis or known to have a positive purified protein derivative (PPD) test result.
Consider prophylaxis for herpes zoster, Pneumocystis jirovecii, and fungal infection while receiving Gamifant. Employ surveillance testing during treatment with Gamifant.
Closely monitor patients receiving Gamifant for signs or symptoms of infection, promptly initiate a complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy.
Increased Risk of Infection With Use of Live Vaccines
Do not administer live or live attenuated vaccines to patients receiving Gamifant and for at least 4 weeks after the last dose of Gamifant. The safety of immunization with live vaccines during or following Gamifant therapy has not been studied.
Infusion-Related Reactions
Infusion-related reactions in patients with primary HLH, including drug eruption, pyrexia, rash, erythema, and hyperhidrosis, were reported with Gamifant treatment in 27% of patients. In one-third of these patients, the infusion-related reaction occurred during the first infusion.
Infusion-related reactions in patients with HLH/MAS in Still’s disease, including pyrexia, headache, paresthesia, bone pain, pruritic rash, and peripheral coldness, were reported with Gamifant treatment in 13% of patients. Infusion-related reactions were reported as mild in 8% of patients and as moderate in 5% of patients.
Monitor patients for infusion-related reactions, which can be severe. Interrupt the infusion for infusion reactions and institute appropriate medical management before continuing infusion at a slower rate.
Adverse Reactions
Primary HLH
Serious adverse reactions were reported in 53% of patients. The most common serious adverse reactions (≥3%) included infections, gastrointestinal hemorrhage, and multiple organ dysfunction. Fatal adverse reactions occurred in 2 (6%) of patients and included septic shock and gastrointestinal hemorrhage.
The most common adverse reactions were (≥10%) for Gamifant included infection (56%), hypertension (41%), infusion-related reactions (27%), pyrexia (24%), hypokalemia (15%), constipation (15%), rash (12%), abdominal pain (12%), CMV infection (12%), diarrhea (12%), lymphocytosis (12%), cough (12%), irritability (12%), tachycardia (12%), and tachypnea (12%).
HLH/MAS
Serious adverse reactions were reported in 12 patients (31%), with the most common serious adverse reaction being pneumonia (5%). Fatal adverse reactions occurred in two patients (5%) and included multiple organ dysfunction and circulatory shock.
The most common adverse reactions (≥10%) for Gamifant included viral infection (44%), rash (21%), anemia (18%), leukopenia (15%), thrombosis (15%), bacterial infections (13%), headache (13%), hyperglycemia (13%), infusion-related reactions (13%), abdominal pain (10%), hypertension (10%), pyrexia (10%), and thrombocytopenia (10%).
References
- Chandrakasan S, Jordan MB, Baker A, et al. Real-world treatment patterns and outcomes in patients with primary hemophagocytic lymphohistiocytosis treatement with emapalumab. Blood Adv. Published online March 1, 2024. doi:10.1182/bloodadvances.2023012217
- Gamifant (emapalumab-lzsg) prescribing information. Stockholm, Sweden: Sobi, Inc. 2022.
- Data on file. Stockholm, Sweden: Sobi, Inc. 2023.
- Sepulveda FE, de Saint Basile G. Hemophagocytic syndrome: primary forms and predisposing conditions. Curr Opin Immunol. 2017;49:20-26. doi:10.1016/j.coi.2017.08.004
- Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041-4052. doi:10.1182/blood-2011-03-278127
- Lehmberg K, Nichols KE, Henter J-I, et al. Consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis associated with malignancies. Haematologica. 2015:100(8):997-1004.
- Marsh RA, Haddad E. How I treat primary haemophagocytic lymphohistiocytosis. Br J Haematol. 2018;182(2):185-199. doi: 10.1111/bjh.15274.
A retrospective review of patients with primary HLH treated with Gamifant® (emapalumab-lzsg)
REAL-HLH is the first real-world study to describe the clinical characteristics, treatment patterns, and outcomes of Gamifant treatment across a large and diverse population of patients who have primary hemophagocytic lymphohistiocytosis (HLH).
< VIEW PIVOTAL TRIAL RESULTS
Study Design1
A retrospective medical chart review was conducted across 33 US hospitals to identify patients treated with ≥1 dose of Gamifant between Nov 20, 2018, and Oct 31, 2021.
Given the complexity of the disease and risk for misclassification, a consistent rule was applied across all enrolled HLH patients and reviewed by a multispecialty panel of experts. Patients were classified as having primary HLH if they met at least 1 of 3 of the following criteria without evidence of underlying malignancy, rheumatologic, or metabolic disease: at least 5 of 8 HLH-2004 diagnostic criteria OR a family history of HLH OR a known genetic mutation associated with primary HLH.
HSCT=hematopoietic stem cell transplantation.
*The REAL-HLH study was a retrospective, noninterventional medical chart review and was not evaluated by the FDA to grant Gamifant approval. Data were extracted from time of Gamifant initiation to end of data availability, end of study (Dec 31, 2021), or death, whichever occurred first.
Demographics1
46 Patients
were included in the analysis
age range: 0.3-21 years old, median: 1 year
39 CHILDREN
0.3-10 years old
7 ADOLESCENTS AND ADULTS
12-21 years old
90%
(27/30) had ≥5 out of 8 HLH-2004 diagnostic criteria
92% (23/25)
80% (4/5)
54.3%
(25/46) had active infections† at diagnosis
51.3% (20/39)
71.4% (5/7)
21.7%
(10/46) had CNS involvement at diagnosis
23.1% (9/39)
14.3% (1/7)
†Viral infections were the most common (72%, 18/25).
DOSING1
‡The recommended starting dose of Gamifant is 1 mg/kg given as an intravenous infusion over 1 hour twice per week.2 Click here for dosing information.
RESULTS
Limitations of analysis: Due to the study design, information could be missing or incomplete, as data may not be uniformly collected or available across all treatment centers. The constrained availability and inconsistent timing of laboratory assessments further hindered comprehensive evaluation of treatment "response." Additionally, safety data were neither collected nor assessed since the study did not incorporate safety-related endpoints. There may be the possibility of a risk of bias toward patients with poor prognoses, as Gamifant is currently indicated for previously treated patients with primary HLH. As patients were concomitantly administered HLH-related therapies, these findings cannot be solely attributed to Gamifant and may not be generalizable beyond the study cohort. The rarity of primary HLH limited the size of the population in this study and the types of analyses that could be performed, particularly when comparing outcomes between children and adolescents/adults.
A majority of patients proceeded to HSCT1
(31/42) of patients treated who were eligible for transplantproceeded to HSCT
time to normalization of laboratory parameters1
The top 5 laboratory parameters for which most of the patients achieved normalization were fibrinogen, absolute neutrophil count, platelets, absolute lymphocyte count, and alanine transaminase.
Select the parameter on the graph below that you would like highlighted.§,‖
Fibrinogen (37/38)
Absolute neutrophil count (40/45)
Platelets (39/46)
Absolute lymphocyte count (30/42)
Alanine transaminase (31/45)
CXCL9 level (24/33)
sCD25 (20/37)
Ferritin (20/45)
Fibrinogen
97.4% patients (37/38)
14 days (range: 1-91 days)3
Absolute lymphocyte count
71.4% patients (30/42)
7 days (range: 3-230 days)3
Absolute neutrophil count
88.9% patients (40/45)
7.5 days (range: 3-63 days)3
Alanine transaminase
68.9% patients (31/45)
26 days (range: 2-113 days)3
CXCL9
72.7% patients (24/33)
28.5 days (range: 4-84 days)3
Ferritin
44.4% patients (20/45)
21.5 days (range: 4-112 days)3
Platelets
84.8% patients (39/46)
8 days (range: 3-76 days)3
sCD25
54.1% patients (20/37)
12.5 days (range: 2-84 days)3
§Laboratory parameters for which data were available for ≥50% of the study population.
‖Normalization of laboratory parameters and biomarker values were based on physician report.
The generalizability of reported results may not correlate with results seen in other real-world setting patients. Continuous variables were summarized using mean, standard deviation (SD), median, and interquartile range (IQR). Categorical variables were described using counts and percentages.
Laboratory parameter normalization breakdown
Fibrinogen
97.4% patients (37/38)
14 days (range: 1-91 days)3
Absolute neutrophil count
88.9% patients (40/45)
7.5 days (range: 3-63 days)3
Platelets
84.8% patients (39/46)
8 days (range: 3-76 days)3
Absolute lymphocyte count
71.4% patients (30/42)
7 days (range: 3-230 days)3
Alanine transaminase
68.9% patients (31/45)
26 days (range: 2-113 days)3
CXCL9
72.7% patients (24/33)
28.5 days (range: 4-84 days)3
sCD25
54.1% patients (20/37)
12.5 days (range: 2-84 days)3
Ferritin
44.4% patients (20/45)
21.5 days (range: 4-112 days)3
The results from the REAL-HLH study are consistent with the pivotal trial for Gamifant across age groups.