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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 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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