Omalizumab Therapy for Mast Cell-Mediator Symptoms in Patients with ISM, CM, MMAS, and MCAS

doi:10.1016/j.jaip.2019.03.039

The Journal of Allergy and Clinical Immunology: In Practice

Volume 7, Issue 7, September–October 2019, Pages 2387-2395.e3

https://doi.org/10.1016/j.jaip.2019.03.039 Get rights and content

Background

Patients with mast cell diseases may suffer from various distressing symptoms, which can be insufficiently controlled with available therapies, severely affecting their quality of life. There is a need for new and safe treatment options for these patients.

Objectives

We aimed to evaluate safety and efficacy of omalizumab administration in patients with a symptomatic mast cell disorder.

Methods

We included 55 patients with a mast cell disorder associated with debilitating symptoms who received omalizumab treatment between January 2015 and December 2017, after a multidisciplinary team meeting at the French National Reference Center for Mastocytosis.

Results

A complete response was achieved for 1 patient (1.8%), a major response for 30 patients (54.5%), and a partial response for 12 patients (21.8%), resulting in an overall best response rate of 78.2% (43 of 55 patients). The response was persistent at least 3 months in 33 of 43 responding patients (76.7%). At the last follow-up, the final overall response rate was 58.2% (32 of 55 patients). Median time to first response was 2 months and median time to best response was 6 months. Omalizumab was dramatically effective on all superficial and general vasomotor symptoms and on most gastrointestinal or urinary symptoms, and partially effective on most neuropsychiatric symptoms. Safety profile was acceptable, except for one severe adverse event (edema of the larynx and dyspnea after the first injection of omalizumab). Side effects were reported in 16 patients (29%), mainly of low to mild intensity, yet causing interruption of treatment in 5 patients (9%).

Conclusion

Omalizumab seems to be a useful therapeutic option to control mast cell–mediator symptoms and displays a favorable safety profile.

Section snippets

Patients

From January 2015 to December 2017, the national multidisciplinary expert team from the CEREMAST recommended treatment with omalizumab for 65 patients with symptomatic mast cell disorder, treated in 11 different centers in France and Belgium. Patients had severe or debilitating symptoms refractory to classical treatments of mast cell disorders, including antihistamines, cromolyn sodium, or leukotriene inhibitors. According to CEREMAST rules of functioning, patients with such treatment decision

Patients

Fifty-five patients with a confirmed diagnosis of mast cell disorder according to the WHO criteria and treated with omalizumab were included in this study. Median age at diagnosis was 41 years (2-87 years), and median age at treatment with omalizumab was 48 years (17-93 years).

The diagnoses were ISM (29 patients, 52.7%), MCAS (15 patients, 27.3%), and CM (11 patients, 20%). Of 55 patients, 49 were evaluated for KIT mutation; KIT D816V mutation was found in 27 of 49 patients (55.1%): 23 of 28

Discussion

This study presents data on the efficacy and safety of omalizumab in mast cell disorders, mainly primary MCAS (ISM, CM, and MMAS) and nonclonal idiopathic MCAS. We included 55 patients in this analysis, which is, to our knowledge, the largest cohort to date because only 29 patients with SM-treated omalizumab have been reported so far, in 10 different series.12, 13, 14, 15, 16, 17, 18, 19, 20, 21

We observed an overall response rate of 78.2% in our series, which is in line with the overall

Acknowledgments

RL, GF, LF, SB, DC, LL, JR, MA, OL, and OH conceptualized and designed the study. RL, GF, LT, MV, CBL, and LL collected and assembled the data. RL, GF, JR, MA, OL, and OH analyzed and interpreted the data. RL, GF, JR, MA, OL, and OH wrote the original draft of the manuscript. RL, GF, and OH reviewed, edited, and finally validated the manuscript.

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: No funding was received for this work.

: Conflicts of interest: The authors declare that they have no relevant conflicts of interest.

^∗: These authors contributed equally to this work.

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Original ArticleOmalizumab Therapy for Mast Cell-Mediator Symptoms in Patients with ISM, CM, MMAS, and MCAS

Background

Objectives

Methods

Results

Conclusion

Section snippets

Patients

Patients

Discussion

Acknowledgments

Blood

J Allergy Clin Immunol

Immunol Allergy Clin North Am

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Biomed Inform

Blood

J Invest Dermatol

J Immunol Methods

J Autoimmun

J Allergy Clin Immunol

J Allergy Clin Immunol

Immunomodulatory mast cells: negative, as well as positive, regulators of immunity

Nat Rev Immunol

Advances in the classification and treatment of mastocytosis: current status and outlook toward the future

Cancer Res

Original Article
Omalizumab Therapy for Mast Cell-Mediator Symptoms in Patients with ISM, CM, MMAS, and MCAS