to 0, 1, or 2 prior regimens for SM. The study excluded patients with serum creatinine > 2.0 mg/dL, hepatic transaminases > 2.5 x upper limit of normal (ULN) or > 5 x ULN if disease-related, total bilirubin > 1.5 x ULN or > 3 x ULN if disease-related, QTc > 450 msec, cardiovascular disease including left-ventricular ejection fraction < 50%, or any pulmonary infiltrates. In addition, the study excluded patients with acute-stage or life-threatening AHN. Patients received RYDAPT 100 mg orally twice daily in 28-day cycles until disease progression or intolerable toxicity.
Of the 116 patients treated, a study steering committee identified 89 patients who had measurable C-findings and were eva luable for response. The median age in this group was 64 years (range: 25 to 82), 64% of patients were male, and nearly all patients (97%) were Caucasian. Among these patients, 36% had prior therapy for SM, and 82% had the KIT D816V mutation detected at baseline. Their median duration of treatment was 11 months (range: < 1 to 68 months), with treatment ongoing in 17%.
Efficacy was established on the basis of confirmed complete remission (CR) plus incomplete remission (ICR) by 6 cycles of RYDAPT by modified Valent criteria for ASM and SM-AHN (Table 7). Table 7 shows responses to RYDAPT according to modified Valent criteria. Confirmed major or partial responses occurred in 46 of 73 patients with a documented KIT D816V mutation, 7 of 16 with wild-type or unknown status with respect to KIT D816V mutation, and 21 of 32 having prior therapy for SM.
Table 7: Efficacy of RYDAPT in Systemic Mastocytosis per Modified Valent Criteria (Study 2)
Modified Valent Criteria: All patients
eva luated e
(N = 89) ASM
(N = 16)
SM-AHN
(N = 57)
MCL
(N = 16)
CR+ICR by 6 cycles, n a, b
(95% CI, %) 19 (21%)
(13, 31) 6 (38%)
(15, 65) 9 (16%)
(7, 28) 4 (25%)
(7, 52)
Median Duration of CR+ICR (months) c
(95% CI)
Range d NR
(24.1, NE)
6.6+, 65.8+ NR
(24.1, NE)
12.1+, 36.8+ NR
(7.4, NE)
6.6+, 52.1+ NR
(NE, NE)
19.1+, 65.8+
Median Time to CR+ICR (months)
Range 0.5
0.1, 3.0 0.7
0.3, 1.9 0.5
0.1, 3.0 0.3
0.1, 0.5
NE: Not Estimated; NR: Not Reached
a Per Study Steering Committee. Response confirmation after ≥ 8 weeks was required. No CRs were reported.
b Patients who received concomitant high-dose corticosteroids were considered uneva luable and were excluded from response assessment.
c Among patients with a response of CR or ICR. The estimated median follow-up for duration of response was 35.4 months overall.
d A + sign indicates a censored value.
e 25 patients were not assessable for the presence of MCL on central histopathology review, and 11 patients with unconfirmed presence of AHN were regarded as not having AHN.
As a post-hoc exploratory analysis, efficacy was also assessed per the 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on Mastocytosis (IWG-MRT-ECNM) consensus criteria. Response after 6 cycles of RYDAPT was determined using a computational algorithm. The efficacy of RYDAPT for MCL was based on the CR results by IWG-MRT-ECNM. There were 115 patients eva luable for response assessment, o
