Table 4.

IWG-MRT-ECNM consensus response criteria for patients with ASM, MCL, and SM associated with a myeloid neoplasm

Complete remission (CR)*

Requires all 4 criteria and response duration must be ≥ 12 wk

No presence of compact neoplastic mast cell aggregates in the BM or other biopsied extracutaneous organ

Serum tryptase level < 20 ng/mL†

Peripheral blood count remission defined as ANC ≥ 1 × 109/L with normal differential, Hb level ≥ 11 g/dL, and platelet count ≥ 100 × 109/L

Complete resolution of palpable hepatosplenomegaly and all biopsy-proven or suspected SM-related organ damage (CI findings)‡

Partial remission (PR)*

Requires all 3 criteria and response duration must be ≥ 12 wk, in the absence of both CR and progressive disease (PD)

Reduction by ≥ 50% in neoplastic MCs in the marrow and/or or other extracutaneous organ at biopsy demonstrating eligible SM-related organ damage

Reduction of serum tryptase level by ≥ 50%†

Resolution of 1 or more biopsy-proven or suspected SM-related organ damage (CI finding(s)) ‡

Clinical improvement (CI)*

Response duration must be ≥ 12 wk

Requires 1 or more of the nonhematologic and/or hematologic response criteria to be fulfilled (see Table 3) in the absence of both CR/PR

assignment or progressive disease (PD)

Stable disease (SD)

Not meeting criteria for CR, PR, CI, or PD

Progressive disease (PD)§

Requires at least 1 element of either criteria 1 or 2 and duration must be ≥ 8 wk

(1) For patients with baseline grade 2 nonhematologic organ damage: a) worsening by 1 grade, AND b) minimum 100% increase (doubling) of laboratory abnormality.

For patients with baseline ≥ grade 2 albumin: (a) worsening by 1 grade, AND (b) decrease by ≥ 0.5 g/dL.

For patients with baseline ≥ grade 3 nonhematologic organ damage: minimum 100% increase (doubling) of laboratory abnormality.

For patients with baseline ≥ grade 2 transfusion-independent anemia or thrombocytopenia: New transfusion dependence of ≥ 4 units of RBCs or platelets at 8 wk.

For patients with baseline transfusion-dependent anemia or thrombocytopenia: ≥100% increase in the average transfusion frequency for an 8-wk period compared with the 12-wk pretreatment period

For patients with baseline grade ≥ grade 3 neutropenia: (a) > 50% decrease in neutrophil count, AND (b) absolute decrease of neutrophil count of ≥ 250/mm3, AND c) grade 4

(2) Development of at least 10-cm palpable symptomatic splenomegaly for a baseline spleen size of not palpable or ≤ 5 cm, OR if baseline symptomatic splenomegaly is > 5 cm, a > 50% worsening and development of at least 10 cm of palpable symptomatic splenomegaly compared with the baseline value.¶

Loss of response (LOR)

Loss of a documented CR, PR, or CI that must be for ≥8 wk. Downgrading of CR to PR or PR to CI is considered as such but is not considered as loss of response unless CI is also lost for a minimum of 8 wk. The baseline value for LOR is the pretreatment measurement(s) and not the nadir values during response.

Guidelines for adjudicating response are as follows: (1) Only disease-related ≥ grade 2 organ damage is evaluable as a primary endpoint in clinical trials. (2) Response adjudications of CR, PR, SD, PD, and LOR should only be applied to these ≥ grade 2 organ damage findings in the context of trials. (3) Disease status at the time of patient removal from the study singularly relates to the updated status of initial ≥ grade 2 organ damage finding(s). (4) Exclusion of drug-related toxicity and/or other clinical issues (eg, gastrointestinal tract bleeding in the case of worsening anemia/transfusion-dependence) should be undertaken before assigning the designation PD or LOR in a patient with worsening of baseline ≥ grade 2 organ damage.

^*Responses that are not maintained or confirmed for a period of at least 12 wk do not fulfill criteria for CR, PR, or CI; however, both maintained and unmaintained (< 12-wk duration) responses in organ damage should be recorded to determine median duration of response.

^†Only valid as a response criterion if the pretreatment serum tryptase level is ≥ 40 ng/mL.

^‡Biopsy of organ(s) in addition to the BM to evaluate for SM-related organ damage may be considered.

^§Preservation of at least one CI finding permits a patient to maintain the response of 'CI' if 1 or more CI findings are lost but none meet criteria for progressive disease (PD). However, if 1 or more of the CI findings become PD, then the CI finding assignment is lost and the patient meets criteria for PD. The baseline value for evaluating PD is the pretreatment measurement(s). The PD findings must be considered related to the underlying disease and not to other clinical factors. Progression of an underlying chronic myeloid neoplasm to AML is also considered PD in the setting of clinical trials.

^¶For clinical trials using 3D computed tomography or magnetic resonance imaging as an additional modality to quantify organomegaly, progression in splenomegaly is defined as an increase in spleen volume of at least 25%.