Page 1339 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 72 Mast Cells and Mastocytosis 1185

The median OS for all patients at 3 years was 57%, consisting of least 12 weeks. The criteria for stable disease, PD, and loss of
74% for patients with SM-AHN, and 43% and 17% for ASM and response were also detailed in the report.
MCL patients, respectively. The strongest risk factor for a poor OS
was a diagnosis of MCL. In addition, inferior survival was observed
in patients undergoing reduced-intensity versus fully myeloablative FUTURE DIRECTIONS
conditioning. However, patient age, donor age, donor type (sibling
or unrelated donor), graft source (BM or peripheral HSCT, KIT Several clinical and translational initiatives are being pursued in MC
mutation status, karyotype), and total-body irradiation used in disease and should reach fruition in the near future. Given the relatively
myeloablative conditioning had no impact on overall or progression- low incidence of SM, efforts are currently being led by the ECNM to
free survival. Treatment-related mortality at 6 months and 1 year was combine patient data from multiple collaborators into a central registry
11% and 20%, respectively, and was highest in MCL patients. (e.g., such data should be useful in generating prognostic variables to
Although a prospective trial is needed to better define the role of help risk stratify patient outcomes). Efforts are also underway to vali-
HSCT in advanced SM, these data suggest that transplantation can date SM-specific patient-reported outcome tools to qualitatively and
provide extended survival in selected patients, particularly for patients quantitatively measure patients’ symptom burden and quality of life.
with SM-AHN. Regulatory health agencies are increasingly focused on these patient
measures for drug approval, and validated patient-reported outcomes
are critical for stringent adjudication of treatment-related changes in
Response Criteria for Advanced SM the context of placebo-controlled, double-blind study designs.
Clinical trials are under development to investigate targets and
Response criteria for advanced SM were first published in 2003 and pathways relevant to MC pathobiology. Novel approaches include
5
reiterated in a consensus conference report in 2007. In this system, use of the anti-CD30 antibody-drug immunoconjugate brentux-
evaluation of clinical evidence of organ damage, or “C” findings, was imab vedotin, JAK inhibitors (e.g., ruxolitinib), PI3K inhibitors,
the foundation for distinguishing levels of response. Changes in BM and BTK inhibitors such as ibrutinib. In addition, new selective
MC burden, serum tryptase level, and hepatosplenomegaly were inhibitors of KIT D816V entered phase I trials in 2016. Other
additionally employed to subcategorize levels of MR. These original agents that merit investigation include inhibitors of BCL-2, agonist
criteria or their modified version have been used to adjudicate antibodies against inhibitory receptors such as siglec-8 in order to
responses in clinical trials of new agents. induce MC apoptosis, and antibodies against other newly described
According to prior consensus response criteria, a MR is defined aberrant markers on neoplastic MCs, such as CD123 (IL-3
as normalization of one or more “C” findings. In turn, MR is divided receptor-α). Biologic correlates of therapeutic response such as
into three subcategories: (1) complete remission (resolution of abnor- changes in KIT mutant allele burden, circulating tumor DNA, and
mal MC infiltrates in organs, decrease of serum tryptase below 20 ng/ cytokine profiles are now being incorporated into trials. Transcrip-
mL, and disappearance of SM-associated organomegaly); (2) incom- tome and proteomic profiling of purified MCs and AHN cell popu-
plete remission (decrease of MC infiltrates and/or serum tryptase lations are compelling translational objectives for future protocols.
level, and/or visible regression of organomegaly by >50%), and (3)
pure clinical response (without decrease of MC infiltrates, serum
tryptase level, or organomegaly). A PR is defined as incomplete REFERENCES
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