Kreitman RJ, et al. ASCO 2018:7004

Moxetumomab pasudotox in heavily pretreated patients with relapsed/refractory hairy cell leukemia: Results of a pivotal international study


Cluster of differentiation 22 (CD22) is highly expressed in hairy cell leukemia (HCL), a rare B-cell malignancy.1 Moxetumomab pasudotox is a recombinant immunotoxin that targets CD22 and could therefore meet the need for new treatments in patients with HCL.2 At the 2018 ASCO Annual Meeting, Dr. Kreitman presented results from a multicentre study that evaluated the efficacy and safety of moxetumomab pasudotox in patients with relapsed/refractory (R/R) HCL.3

Study design

  • This single-arm, open-label study enrolled 89 patients from 34 centres in 14 countries.
  • Key inclusion criteria were:
    • Histologically confirmed HCL and at least one of the following:
      • Neutrophils <1.0 × 109/L;
      • Platelets <100 × 109/L;
      • Hemoglobin <10 g/dL; or
      • Symptomatic splenomegaly.
    • At least two prior systemic therapies;
    • Eastern Cooperative Oncology Group performance status of 0–2; and
    • Adequate hepatic and renal function.
  • Moxetumomab pasudotox was given intravenously at a dose of 40 µg/kg on days 1, 3, and 5 of a 28-day cycle, with a maximum of six treatment cycles.
    • Treatment was discontinued upon disease progression, the start of an alternate therapy, or unacceptable toxicity.
    • There was also an option to discontinue treatment if the patient achieved a minimal residual disease (MRD)-negative complete response (CR), as assessed by the investigator using flow cytometry.
  • The primary endpoint was the rate of durable CR, defined as CR with hematologic remission (HR) lasting at least 181 days.
    • CR was assessed by blinded independent central review and was defined as:
      • HR lasting at least four weeks;
      • No leukemic cells in bone marrow, as measured by hematoxylin and eosin staining; and
      • No hepatomegaly, splenomegaly, or lymphadenopathy, as measured by computed tomography or magnetic resonance imaging.
    • HR was defined as:
      • Neutrophils ≥1.5 × 109/L;
      • Platelets ≥100 × 109/L;
      • Hemoglobin ≥11 g/dL; and
      • No transfusions/growth factors for at least four weeks.
  • Secondary endpoints included overall response rate, CR rate, duration of response, duration of CR, tolerability, safety, pharmacokinetics, and immunogenicity.
    • Disease response and immunohistochemistry MRD were assessed by blinded independent review.

Key findings

Baseline characteristics and disposition

  • A total of 80 patients received treatment and follow-up.
    • Of those, 50 patients completed six cycles (62.5%).
  • Twelve patients (15%) discontinued because of MRD-negative CR in less than six cycles of treatment.
    • Other reasons for treatment discontinuation included:
      • Adverse event (AE) (n = 12, 15%), of which eight patients (10%) experienced a treatment-related AE;
      • Death (n = 1, 1.3%);
      • Disease progression (n = 2, 2.5%); and
      • Lack of benefit (n = 3, 3.8%).
  • Median duration of follow-up was 16.7 months as of the data cutoff, which was May 24, 2017.
  • Fifty patients (62.5%) are ongoing in follow-up.
  • Reasons for study discontinuation during follow-up included:
    • Disease progression or new HCL treatment (n = 24, 30%);
    • Death (n = 3, 3.8%);
    • Withdrawal of consent (n = 2, 2.5%); and
    • Lost to follow-up (n = 1, 1.3%).
  • The median age of all patients was 60.0 years (range: 34–84).
  • The majority of patients were male (79%).
  • Median blood laboratory values were as follows:
    • Hemoglobin: 11.10 g/dL (range: 6.5–16.3);
    • Neutrophil count: 0.81 × 103/μL (range: 0.1–6.2); and
    • Platelet count: 68 × 103/μL (range: 6–350).
  • Patients had undergone a median of three prior lines of therapy (range: 2–11).
    • Ten patients (13%) had received one prior purine nucleoside analogue (PNA), 30 patients (38%) had received two prior PNAs, and 40 patients (50%) had received more than two prior PNAs.
    • Sixty patients (75%) had received prior rituximab.
    • Fourteen patients (18%) had received a prior serine/threonine-protein kinase B-raf (BRAF) inhibitor.


  • A durable CR was achieved in 30% of patients, as assessed by blinded independent central review.
  • Other response assessments are summarized in Table 1.
  • Sixty-four patients (80%) achieved HR, with a median onset of 1.1 months.
    • Median immunoglobulin levels were unchanged after treatment.
    • Median cluster of differentiation 4 (CD4) T-cell counts were stable or increased, following a transient decrease on Day 8.
  • Median durations of HR and CR were not reached. (Figure 1)
  • Moxetumomab pasudotox cleared rapidly following dosing.
  • There was a sustained B-cell depletion during treatment, with recovery occurring by six months following treatment cessation.
  • There was a high rate of antidrug antibodies (ADA) (59% prevalence at baseline and 88% prevalence after at least one time point), with increasing titer following treatment.
    • Of 41 patients who were ADA-positive at baseline, 100% had ADA specific to the PE38 domain.


  • Treatment-related AEs are summarized in Table 2.
  • Ten patients developed capillary leak syndrome (CLS) and/or hemolytic uremic syndrome (HUS).
    • Three patients had CLS, three patients had HUS, and four patients had both CLS and HUS.
  • CLS and HUS occurred in any treatment cycle.
  • All CLS and HUS events were resolved with supportive care and/or treatment discontinuation (n = 6).
  • Supportive care included the following:
  • Prophylactic oral hydration during the first week of each cycle and proper intravenous fluid supplementation on the day of infusion;
  • Close monitoring of blood pressure, body weight, and blood creatinine;
  • Monitoring of schistocytes in peripheral blood smear if HUS was suspected;
  • Supportive medical care; and
  • Intensive care (without plasma exchange) and treatment discontinuation for severe cases.

Table 1. Disease response and MRD status*

Figure 1. Duration of response

Table 2. Treatment-related adverse events

Key conclusions

  • Moxetumomab pasudotox treatment led to deep, durable responses and eradicated MRD in a substantial proportion of patients with R/R HCL.
  • The tolerability profile was acceptable, with low rates of treatment-related AEs leading to discontinuation.
    • CLS and HUS were manageable and reversible with close monitoring and best supportive care.
  • This non-chemotherapeutic agent has the potential to become a standard of care for patients with R/R HCL.

References: 1. Grever MR, Blachly JS, Andritsos LA. Hairy cell leukemia: update on molecular profiling and therapeutic advances. Blood Rev 2014;28(5):197–203. 2.  Kreitman RJ, Pastan I. Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotox. Clin Cancer Res 2011;17(20):6398–405. 3.  Kreitman RJ, Dearden C, Zinzani PL, et al. Moxetumomab pasudotox in heavily pretreated patients with relapsed/refractory hairy cell leukemia: results of a pivotal international study. J Clin Oncol (ASCO Annual Meeting) 2018;36(Suppl):abstr 7004.