Successful Treatment of Systemic Mastocytosis Associated with AML-M2, t(8:21) in a Child Using MRC-based AML Chemotherapy along with Gemtuzumab

Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts

“…66,69,70 In addition, initial clinical observations suggest that antibody-based drugs exert antineoplastic effects in patients with advanced SM. 72,73 A summary of surface markers and potential targets expressed by neoplastic MCs is shown in Figure 1 and supplemental Table 5. Another emerging approach is to target cell-surface antigens involved in drug resistance.…”

Bone Marrow Mast Cell Antibody-Targetable Cell Surface Protein Expression Profiles in Systemic Mastocytosis

“…So far, only a few single case reports and small patient series that have been treated with antibody-targeted therapies have been reported in the literature. This includes four ASM patients [28] and one smoldering SM (SSM) case [50] treated with daclizumab (anti-CD25), four patients (three ASM and one ASM) treated with brentuximab-vedotin (anti-CD30) [29], one patient diagnosed with SM-AHN, one with MCL receiving gemtuzumab ozogamicin (anti-CD33) [26,27], and several SM patients with distinct subtypes of SM receiving omalizumab (anti-FcεRI) with significant improvement of symptoms but no objective reduction of tumor cell burden in most tested cases (CR: 52%, 11/21, major response: 33%, 7/21, partial response: 14%, 3/21) [54,55,56,57,58,59,60,61,62]. Moreover, some cutaneous mastocytosis (CM) patients have also been successfully treated with omalizumab with CR in 1/3 treated patients [76,77,78].…”

“…In contrast to anti-CD30 and FcϵRI therapy, which were both associated with relatively poor responses in SM (e.g., overall response rate of 50% and 100% based on the improvement of symptoms but with only 52% partial responses, respectively) in the absence of any CR [29,54,55,56,57,58,59,60,61,62], anti-CD25, and anti-CD33 have shown more promising results [26,27,28,50]. Thus, a single dose of daclizumab, which is an anti-CD25 monoclonal antibody, was first administered as immunosuppressive therapy to an SSM patient who underwent a heart transplant.…”

“…However, a limited effect on reducing the BMMC burden, which is associated with severe adverse effects (hypotension, tachycardia, and intense pain in back, hips, and femurs due to the massive release of intracellular MC granules) [28], suggests that daclizumab therapy might have some activity in a small subset of patients with advanced SM. In turn, sustained CR has been reported after anti-CD33 (gentuzumab ozogamicin) in an adult MCL patient who did not respond previously to imatinib, interferon, hydroxyurea, midostaurin, and cladribine [27], and in an SM associated with the AML child who finally died from relapsing AML [26]. In contrast, therapy with the humanized anti-CD30 brentuximab-vedotin antibody, that acts via a potent antimitotic agent (auristatin E) emerged as a potential candidate therapy for SM due to its ability (i) to induce apoptosis on neoplastic MC, (ii) to down-regulate of IgE-mediated histamine release, and (iii) to synergize with midostaurin to inhibit neoplastic MC growth in vitro [79].…”

“…These antibody-targetable cell surface membrane proteins include CD22, CD25, CD30, CD33, CD123, and FcϵRI, which have all been found in tumor MC from SM patients [22] (Table 1). Some of these markers have even been targeted by therapeutic antibodies outside clinical trials, usually in small series of SM patients and single case reports, with variable responses [26,27,28,29]. However, these immuno-phenotypic studies failed to provide information about the patterns of expression of the involved markers within individual patients and across distinct disease subtypes, particularly among advanced SM cases.…”