ASH Clinical News July 2017 V2 - Page 32

CLINICAL NEWS
On Location Updates in Malignant Hematology
co-author Srdan Verstovsek , MD , PhD , from the MD Anderson Cancer Center at the University of Texas in Houston , who reported the results .
Patients enrolled in the phase III , randomized , open-label , multicenter SIMPLIFY 2 trial met the same eligibility criteria as those in the SIMPLIFY 1 trial , with the exception that patients had to have received ruxolitinib for ≥4 weeks and were transfusion-dependent or had required ruxolitinib dose adjustments for grade ≥3 hematologic toxicity .
Patients were stratified according to transfusion dependency and baseline TSS score (< 18 or ≥18 ), then randomized 2:1 to receive 24 weeks of either momelotinib 200 mg once daily ( n = 104 ; mean age = 66.4 years ) or BAT ( n = 52 ; mean age = 69.4 years ). This was an “ advanced ” group of patients , Dr . Verstovsek noted , with median times from MF diagnosis to enrollment of 3.7 years ( range = 0.3-33.5 years ) and 4.0 years ( 0.2-24.9 years ), respectively .
“ About one-third ( n = 38 ; 31 %) of the patients on momelotinib discontinued treatment within the first 24 weeks [ versus ] about a quarter of patients in the BAT arm ( n = 14 ; 23 %),” Dr . Verstovsek reported . “ There were more
AEs – although low-grade – in the momelotinib arm that led to discontinuation .”
As seen in TABLE 2 , the study failed to meet its primary endpoint of momelotinib ’ s non-inferiority to BAT in terms of splenic response rate at 24 weeks . However , momelotinib was superior to ruxolitinib for the secondary endpoints of reducing symptom burden , increasing rates of transfusionindependence , and reducing rates of transfusion-dependence .
“ A majority of patients ( 88 %) in the BAT arm continued ruxolitinib , and , in fact , 27 percent of those patients had a combination of ruxolitinib with another agent ,” he added . “ Only four patients did not receive ruxolitinib .”
More patients in the momelotinib arm than in the BAT arm experienced grade ≥3 treatment-related AEs ( 60 % and 38 %), and , again , anemia and thrombocytopenia were the most common grade ≥3 AEs in both treatment arms :
• anemia : 13 % in the momelotinib arm and 13 % in the ruxolitinib arm
• thrombocytopenia : 7 % in the
TABLE 2 . SIMPLIFY 2 : Primary and Secondary Endpoints at 24 Weeks
Momelotinib
BAT
p Value
Splenic response rate
6.7 %
5.8 %
0.90
TSS response rate
26.2 %
5.9 %
< 0.001
Transfusion requirements ( units / month ), median
0.5
1.2
0.39
Transfusion-independence rate
43.3 %
21.2 %
0.001
Transfusion-dependence rate
50.0 %
63.5 %
0.10
BAT = best available therapy ; TSS = Total Symptom Score
momelotinib arm and 6 % in the ruxolitinib arm
Eleven patients ( 11 %) in the momelotinib arm experienced treatmentemergent PN , three of whom discontinued treatment , but no patients in the BAT arm experienced PN . Overall , Dr . Verstovsek said , “ we did not see new safety concerns emerging with momelotinib in this study .”
Both studies are limited by the use of patient self-report to monitor symptoms .
“ For now , ruxolitinib will remain the only drug approved for MF ,” Dr . Mesa concluded . “ There are ongoing discussions [ about whether momelotinib ] has a place in MF , and , if so , what niche would that be and what the regulatory bodies would accept as a reasonable path [ to approval ].” ●
REFERENCES
1 . Mesa RA , Kiladjian JJ , Catalano JV , et al . Phase 3 trial of momelotinib ( MMB ) vs ruxolitinib ( RUX ) in JAK inhibitor ( JAKi ) naive patients with myelofibrosis ( MF ). Abstract # 7000 . Presented at the 2017 ASCO Annual Meeting , June 6 , 2017 ; Chicago , Illinois .
2 . Harrison CN , Vannucchi AM , Platzbecker U , et al . Phase 3 randomized trial of momelotinib ( MMB ) versus best available therapy ( BAT ) in patients with myelofibrosis ( MF ) previously treated with ruxolitinib ( RUX ). Abstract # 7001 . Presented at the 2017 ASCO Annual Meeting , June 6 , 2017 ; Chicago , Illinois .

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CLINICAL NEWS On Location Updates in Malignant Hematology co-author Srdan Verstovsek, MD, PhD, from the MD Anderson Cancer Center at the University of Texas in Houston, who reported the results. Patients enrolled in the phase III, randomized, open-label, multicenter SIMPLIFY 2 trial met the same eligibil- ity criteria as those in the SIMPLIFY 1 trial, with the exception that patients had to have received ruxolitinib for ≥4 weeks and were transfusion-dependent or had required ruxolitinib dose adjustments for grade ≥3 hematologic toxicity. Patients were stratified according to transfusion dependency and baseline TSS score (<18 or ≥18), then randomized 2:1 to receive 24 weeks of either momelo- tinib 200 mg once daily (n=104; mean age = 66.4 years) or BAT (n=52; mean age = 69.4 years). This was an “advanced” group of patients, Dr. Verstovsek noted, with median times from MF diagnosis to enrollment of 3.7 years (range = 0.3-33.5 years) and 4.0 years (0.2-24.9 years), respectively. “About one-third (n=38; 31%) of the patients on momelotinib discontin- ued treatment within the first 24 weeks [versus] about a quarter of patients in the BAT arm (n=14; 23%),” Dr. Ver- stovsek reported. “There were more AEs – although low-grade – in TABLE 2. SIMPLIFY 2: Primary and Secondary Endpoints at 24 Weeks the momelotinib arm that led to Momelotinib BAT p Value discontinuation.” Splenic response rate 6.7% 5.8% 0.90 As seen in TABLE 2 , the study TSS response rate 26.2% 5.9% <0.001 failed to meet its primary end- Transfusion requirements (units/month), median 0.5 1.2 0.39 point of momelotinib’s non-infe- Transfusion-independence rate 43.3% 21.2% 0.001 riority to BAT in terms of splenic response rate at 24 weeks. How- Transfusion-dependence rate 50.0% 63.5% 0.10 ever, momelotinib was superior BAT = best available therapy; TSS = Total Symptom Score to ruxolitinib for the secondary endpoints of reducing symptom momelotinib arm and 6% in the burden, increasing rates of transfusion- REFERENCES ruxolitinib arm independence, and reducing rates of 1. Mesa RA, Kiladjian JJ, Catalano JV, et al. Phase 3 trial of momelotinib (MMB) vs ruxolitinib (RUX) in JAK inhibitor (JAKi) naive patients transfusion-dependence. with myelofibrosis (MF). Abstract #7000. Presented at the 2017 “A majority of patients (88%) in the Eleven patients (11%) in the momelotinib ASCO Annual Meeting, June 6, 2017; Chicago, Illinois. BAT arm continued ruxolitinib, and, in arm experienced treatment- 2. Harrison CN, Vannucchi AM, Platzbecker U, et al. Phase 3 randomized trial of momelotinib (MMB) versus best available therapy (BAT) in fact, 27 percent of those patients had a emergent PN, three of whom discon- patients with myelofibrosis (MF) previously treated with ruxolitinib combination of ruxolitinib with another tinued treatment, but no patients in the (RUX). Abstract #7001. Presented at the 2017 ASCO Annual Meeting, agent,” he added. “Only four patients did BAT arm experienced PN. Overall, June 6, 2017; Chicago, Illinois. not receive ruxolitinib.” Dr. Verstovsek said, “we did not see More patients in the momelotinib arm new safety concerns emerging with than in the BAT arm experienced grade momelotinib in this study.” ≥3 treatment-related AEs (60% and 38%), Both studies are limited by the use of and, again, anemia and thrombocytopenia patient self-report to monitor symptoms. were the most common grade ≥3 AEs i ( f"r'WƗF"v&VFP&FG&VFVB&3ǒG'Vr&fVBf"b( G"W666VFVB( FW&R&RvrF67W760( V֖2RFRVF"&Х&WBvWFW"VF%26RB2RFR'WƗF"&ФbBb6vB6RvVBFB&R@vBFR&VwVF'&FW2vVB66WB2( F&&7FVrRFP&V6&RFF&f( )xVBf #rSF4VVWFpBW6F*FFvV&v( "FV6V&W""#pW7BƖRW"VWFrF26G06WFrf"WfW'RF66fW"f'&Bg&W6B7&VFfRFFvVGFVFrFRv&N( 27B6&VV6fPVFwWfVBbFRV"wwrVFw&rVVWFsS