CLINICAL NEWS among those > 60 years . These participants tended to be older than those in the original MPN cohort ( 70 % vs . 31 % were > 60 years ).
“ The 0.2 percent prevalence rate of JAK2 V617F in the control cohort is roughly double the estimated age-adjusted prevalence rate of combined JAK2 V617F-positive MPN in the United States based on data from two large health-care plans ,” Dr . Hinds and colleagues explained , noting that the “ excess prevalence of JAK2 V617F clonal hematopoiesis among unselected controls likely represents a combination of persons with an undiagnosed MPN , individuals who may develop a future MPN , and those who will never develop a hematologic disorder .”
An additional 342 other self-reported phenotypes were assessed for V617F carrier status in the population cohort , adjusting for age , gender , and genetic principal components . “ A few of these control individuals , while not enrolled in the MPN research initiative , independently reported having an MPN ,” the authors reported . “ This was strongly associated with V617F carrier status
( odds ratio [ OR ] = 2.38 , P = 5.6 × 10 −27 ).” V617F carriers also reported more blood clots ( OR = 1.8 ; p = 0.014 ), less anemia ( OR = 0.45 ; p = 0.019 ), and higher prevalence of stroke ( OR = 1.9 ; p = 0.03 ), though these associations were not significant after adjustment .
The researchers compared the 726 MPN cases with the total control group , and the 497 V617F carriers in the control population with the remaining 252,150 V617F non-carrier controls . In both analyses , there was a strong association in the 9p24.1 region around JAK2 and 5p22
The first and only oral proteasome inhibitor
• The approval of the NINLARO ® ( ixazomib ) regimen ( NINLARO + lenalidomide + dexamethasone ) was based on a statistically significant ~ 6 month improvement in median progression-free survival vs the placebo regimen ( placebo + lenalidomide + dexamethasone ) — Median PFS : 20.6 vs 14.7 months ( 95 % CI , 17.0-NE and 95 % CI , 12.9-17.6 , respectively )
- HR = 0.74 ( 95 % CI , 0.587-0.939 ); P = 0.012
steatosis , hepatitis cholestatic and hepatotoxicity have each been reported in < 1 % of patients treated with NINLARO . Events of liver impairment have been reported ( 6 % in the NINLARO regimen and 5 % in the placebo regimen ). Monitor hepatic enzymes regularly during treatment and adjust dosing as needed .
• Embryo-fetal Toxicity : NINLARO can cause fetal harm . Women should be advised of the potential risk to a fetus , to avoid becoming pregnant , and to use contraception during treatment and for an additional 90 days after the final dose of NINLARO .
ADVERSE REACTIONS The most common adverse reactions ( ≥ 20 %) in the NINLARO regimen and greater than the placebo regimen , respectively , were diarrhea ( 42 %, 36 %), constipation ( 34 %, 25 %), thrombocytopenia ( 78 %, 54 %; pooled from adverse events and laboratory data ), peripheral neuropathy ( 28 %, 21 %), nausea ( 26 %, 21 %), peripheral edema ( 25 %, 18 %), vomiting ( 22 %, 11 %), and back pain ( 21 %, 16 %). Serious adverse reactions reported in ≥ 2 % of patients included thrombocytopenia ( 2 %) and diarrhea ( 2 %).
SPECIAL POPULATIONS
• Hepatic Impairment : Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment .
• Renal Impairment : Reduce the NINLARO starting dose to 3 mg in patients with severe renal impairment or end-stage renal disease requiring dialysis . NINLARO is not dialyzable .
• Lactation : Advise women to discontinue nursing while on NINLARO .
DRUG INTERACTIONS : Avoid concomitant administration of NINLARO with strong CYP3A inducers .
TOURMALINE-MM1 : a global , phase 3 , randomized ( 1:1 ), double-blind , placebo-controlled study that evaluated the safety and efficacy of NINLARO ( an oral PI ) vs placebo , both in combination with lenalidomide and dexamethasone , until disease progression or unacceptable toxicity in 722 patients with relapsed and / or refractory MM who received at least 1 prior therapy .
MM = multiple myeloma ; NE = not evaluable ; PFS = progression-free survival ; PI = proteasome inhibitor .
Please see adjacent Brief Summary .
USO / IXA / 16 / 0100
ixazomib as a category 1 treatment option for previously treated multiple myeloma . 1