Investigators from the European Competence Network on Mastocytosis and the American Initiative on Mast Cell Diseases have proposed refined response criteria for patients with advanced systemic mastocytosis (AdvSM).

The updated response criteria utilizes a tiered approach including pathologic, molecular and cytogenetic, clinical, and symptom/quality of life responses, as published in the Journal of Allergy and Clinical Immunology: In Practice.

“Several disease factors render response assessment in AdvSM complex and difficult. This is relevant to adjudication of patients on clinical trials as well as for practicing physicians. In a majority of patients, AdvSM is a multi-mutated stem-cell disorder affecting multiple cell lineages,” the authors said.

“Given the increasing focus on pathologic response, the aforementioned evidence of its correlation with long-term outcomes, and the challenges of interpreting C-findings, we have proposed response criteria based on a modular approach where these parameters are uncoupled from each other and evaluated in a tiered approach.”

The response criteria has 4 main tiers for the evaluation of treatments and improvement of disease. Tier 1 is broken into 2 parts: 1A, which is focused on pathological responses including mast cell infiltration of bone marrow, serum tryptase levels, and complete blood count; and 1B, which is evaluated if associated hematologic neoplasms are present and focuses on the responses of monocytes/eosinophils/blasts.

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Tier 2 focuses on the molecular response of KIT D816V through allele-specific polymerase chain reaction (PCR) or digital droplet PCR. The third tier, Tier 3, monitors clinical response to intervention through changes in the International Working Group Criteria. The final tier, Tier 4, follows responses in symptoms and changes in quality of life through the AdvSM symptom assessment form and other patient reported outcomes.

Tier 1A criteria would serve as primary endpoints in clinical trials while the other tiers could serve as secondary endpoints, the authors said. They did warn that there may be a tendency for clinical practice to focus on Tier 1 criteria, some of the other criteria may be more closely aligned to desired patient outcomes such as changes in symptoms and quality of life.

Response criteria have undergone several modifications over the years as more is understood about the disease and new treatments are discovered. The first criteria, the Valent criteria, were released in 2003 and focused on bone marrow mast cell burden and serum tryptase levels along with minimal changes in laboratory C-findings.

Updated criteria were generated from the Mayo Clinic in 2010 and focused on disease-related symptoms, organomegaly/lymphadenopathy, organ damage, and bone marrow findings. Modified Valen response criteria, which specified minimal criteria for improvement of C-findings and also incorporated modified Cheson response criteria for transfusions of red blood cells and platelets, were utilized during the global trial of midostaurin between 2009 and 2013.

The International Working Group for Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis published new criteria in 2013 that sought to establish more stringent, well-defined, and clinically-relevant definitions for organ damage and treatment responses.


Gotlib J, Schwaab J, Shomali W, et al. Proposed ECNM-AIM response criteria in advanced systemic mastocytosis. J Allergy Clin Immunol Pract. Published online June 17, 2022. doi:10.1016/j.jaip.2022.05.034