A phase 2 study of brentuximab vedotin in patients with CD30-positive advanced systemic mastocytosis

Jason Gotlib, John H. Baird, Tracy I. George, Cheryl Langford, Isabel Reyes, Justin Abuel, Cecelia Perkins, Kurt Schroeder, Prithviraj Bose and Srdan Verstovsek

Data supplements

Article Figures & Data


  • Figure 1.

    Baseline and on-treatment MC CD30 expression and BM MC burden. CD30+ BM MCs (A), assessed by multiparameter flow cytometry on the aspirate specimen, as well as BM MC burden (B), BM MC burden, assessed by immunohistochemistry on the core biopsy specimen, did not show significant reductions when compared with pretreatment baseline by Wilcoxon matched pairs signed rank test (i). Pre- and posttherapy assessments are represented for individual patients (i) and for the entire cohort (ii) with each biomarker. Box plot boundaries represent the 75th and 25th percentiles; whiskers denote maximum and minimum values, (+) denotes the cohort’s mean, and symbols represent individual patient values. EOT, end of treatment; FCM, multiparametric flow cytometry; IHC, immunohistochemistry.

  • Figure 2.

    Changes in serum tryptase levels on BV therapy. Serum tryptase activity level, represented for each patient as a percentage change relative to their pretreatment baseline, did not show durable reductions over the course of treatment. Patient 3 discontinued treatment after cycle 4 because of progressive disease, with subsequent values obtained during posttherapy monitoring shown within the dashed line box.

  • Figure 3.

    Changes in patient-reported symptoms on BV therapy. Composite symptom burden assessments using the MPN-SAF TSS-10* (A) and modified MSAF** (B) did not show significant change over time (r2 ∼0) by 1-way analysis of variance with a posttest for linear trend (i). Individual patients’ assessments (ii) did not show a consistent trend over time. *Composite of patient-reported scores on 10 items (0-10 scale each, with higher indicating worse): worst fatigue, concentration, early satiety, inactivity, night sweats, itching, bone/muscle pain, abdominal discomfort, weight loss, and fever. **Composite of patient-reported scores on 10 items (0-10 scale each, with higher indicating worse): pruritus, dizziness, headache, worst fatigue, flushing, abdominal discomfort, diarrhea, bone/muscle pain, concentration, and depression.


  • Table 1.

    Baseline characteristics of patients

    CharacteristicsOverall population (N = 10)
    Median age (range), y72.5 (40-84)
    Female sex, n (%)6 (60)
    ECOG performance status, n (%)
     0-17 (70)
     2-33 (30)
    Median number of prior therapies (range), n0.5 (0-2)
    Number of prior therapies per patient, n (%)
     05 (50)
     14 (40)
     21 (10)
    Type of prior therapy, n (%)
     Splenectomy3 (30)
     Cladribine3 (30)
     Midostaurin1 (10)
     Imatinib1 (10)
     Decitabine*1 (10)
    Clinicopathologic diagnosis, n (%)
     ASM3 (30)
     SM-AHN5 (50)
      CMML-13 (30)
      MDS/MPN-U1 (10)
      CEL, NOS1 (10)
     MCL2 (20)
      CMML-11 (10)
    Mutation status, n (%)
     KIT D816V mutation10 (100)
    Median number of IWG-MRT-ECNM organ damage findings (range), n1 (1-3)
    Number of IWG-MRT-ECNM organ damage findings per patient, n (%)
     16 (60)
     22 (20)
     32 (20)
    Types of IWG-MRT-ECNM organ damage findings, n (%)
     Elevated alkaline phosphatase5 (50)
     Symptomatic splenomegaly3 (30)
     Anemia4 (40)
      Transfusion-dependent2 (20)
      Transfusion-independent2 (20)
     Thrombocytopenia4 (40)
      Transfusion-dependent2 (20)
      Transfusion-independent2 (20)
     Neutropenia1 (10)
     Ascites1 (10)
    Median serum tryptase (range), ng/mL295 (81-903)
    Median bone marrow core biopsy mast cell burden (range), % involvement55 (15-60)
    Median bone marrow mast cell CD30+ expression (range), %70 (29-96)
    • * AHN-directed therapy for MDS/MPN-U.

    • For the full listing and definitions of eligible organ damage criteria, please see the IWG-MRT-ECNM consensus guidelines.29

    • Measured via tryptase, CD117, and CD25 immunohistochemistry staining on the core biopsy specimen.

    • Measured via multiparametric FCM methods using anti-BerH83 antibody on aspirate specimen.

    • CEL, chronic eosinophilic leukemia, not otherwise specified; CMML-1, chronic myelomonocytic leukemia, <10% blasts; ECOG, Eastern Cooperative Oncology Group; KIT, CD117, c-Kit receptor; MCL, mast cell leukemia; MDS/MPN-U, myelodysplastic/myeloproliferative neoplasm, unclassifiable; MPN-SAF, Myeloproliferative Neoplasm Symptom Assessment Form.

  • Table 2.

    Efficacy summary

    IWG-MRT-ECNM response*, n (%)Overall population (N = 10)
    ORR (CR + PR +CI)0 (0)
    Stable disease8 (80)
    Progressive disease1 (10)
    Not evaluable1 (10)
    • For the full listing and definitions of response criteria, please see the IWG-MRT-ECNM consensus guidelines.29

    • CI, clinical improvement

  • Table 3.

    Adverse events reported on study, regardless of attribution

    Overall population (N = 10)Any grade, n (%)Grade 3/4, n (%)Grade 5, n (%)
     Fatigue4 (40)
     Infusion reaction2 (20)
     Abdominal pain2 (20)
     Anorexia2 (20)
     Vomiting2 (20)
     Diarrhea2 (20)
     Constipation2 (20)
     Cough2 (20)
     Dyspnea2 (20)
     Depression2 (20)
     Rash1 (10)1 (10)
     Peripheral neuropathy1 (10)*
     Neutropenia3 (30)
     Anemia2 (20)1 (10)
     Thrombocytopenia1 (10)
    Serious adverse events
     Intracranial hemorrhage1 (10)
     Portal vein thrombosis1 (10)
     Epiglottitis1 (10)
     Pleural effusion1 (10)
    • * Pretreatment grade 1 neuropathy worsened to grade 2 after 1 cycle of BV, but subsequently returned to baseline without dose modification.

    • All grade 4 events, required dose holds for 1 wk (n = 1) and 3 wk (n = 2); 1 patient required dose reduction of BV for cycle 7 after 2 successive dose holds.

    • All SAEs were considered unrelated to BV.

    • Patient died of an intracranial hemorrhage resulting from a mechanical fall during cycle 1 of BV in the setting of thrombocytopenia.