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CLINICAL NEWS ciloleucel at doses of 0.5x10 6 cells / kg , 1 × 10 6 cells / kg , and 2 × 10 6 cells / kg ). Those with prior blinatumomab exposure were excluded from the 2 × 10 6 dosing group .

As with clinical trial experiences of axicabtagene ciloleucel in lymphoma , cytokine release syndrome ( CRS ) and neurotoxicity were common adverse events ( AEs ) among these patients :

• CRS : 21 ( 91 %) any-grade and 5 ( 22 %) grade ≥3 AEs

• Neurotoxicity : 18 ( 78 %) any-grade and 12 ( 52 %) grade ≥3 AEs

The researchers did not observe any significant differences in CRS rates between blinatumomab-naïve and blinatumomab-exposed groups , and “ all [ of these events ] resolved , and the two patient deaths , one in each group , were related exclusively to disease progression ,” Dr . Shah reported .

Among the efficacy-evaluable population , 13 patients ( 72 %) had CR or CRi . Blinatumomab exposure did not appear to affect CR / CRi rates : 63 percent ( n = 5 / 8 ) and 80 percent ( n = 8 / 10 ) among those with and without blinatumomab , respectively ( p value not reported ).

Overall , 17 patients ( 94 %) achieved undetectable minimal residual disease ( MRD ) and , again , this did not appear to differ based on blinatumomab exposure ( 88 % with and 100 % without ).

“ Among six evaluable patients who did not respond to prior blinatumomab , five had undetectable MRD response to axicabtagene ciloleucel ,” Dr . Shah noted . He also reported that there were no major differences in CAR T-cell manufacturing success or CAR T-cell expansion between the two groups .

“ These results are reassuring [ and ] show we can be less apprehensive with our sequencing of these therapies ,” Dr . Shah concluded . However , he added that the findings were limited by the small patient population and potentially confounded by the fact that CAR T-cell dose infusions differed between patients with and without blinatumomab exposure .

The authors report financial relationships with Kite Pharma and Amgen , the manufacturers of KTE-C19 and blinatumomab , respectively .

REFERENCE

Shah BD , Oluwole OO , Baer MR , et al . Outcomes of patients ( pts ) treated with prior blinatumomab ( Blin ) in ZUMA-3 : A study of KTE-C19 , an anti-CD19 chimeric antigen receptor ( CAR ) t cell therapy , in adult pts with relapsed / refractory acute lymphoblastic leukemia ( R / R ALL ). Abstract # 7006 . Presented at the 2018 ASCO Annual Meeting , June 2 , 2018 ; Chicago , IL .

Attendees at the 2018 ASCO Annual Meeting .

In a phase II study of patients with Waldenström macroglobulinemia ( WM ), treatment with the highly selective Bruton tyrosine kinase ( BTK ) inhibitor acalabrutinib led to an overall response rate ( ORR ) of 93 percent , with 27 months of follow-up . The efficacy was observed across patients with both treatment-naïve and relapsed / refractory disease , according to results presented at the 2018 ASCO Annual Meeting .

“ Ibrutinib is an approved BTK inhibitor with demonstrated activity in WM , yet treatment with ibrutinib has been associated with toxicities such as bleeding and atrial fibrillation ,” said lead author Roger Owen , MRCP , MRCPath , MD , of St . James ’ University Hospital in Leeds , U . K . “ Acalabrutinib is a highly selective BTK inhibitor with minimal off-target activity .”

The phase II trial enrolled adults with WM without prior BTK inhibitor exposure or significant cardiovascular disease ; patients who had prior or concurrent atrial fibrillation were permitted in the study . Among the 116 patients ( n = 14 treatment-naïve and n = 92 relapsed / refractory ) enrolled as of February 13 , 2018 , the median patient age was 69 years ( range = 39-90 years ). In the relapsed / refractory group , patients had received a median of two prior therapies ( range = 1-7 therapies ), the most common of which was rituximab .

Patients received acalabrutinib 100 mg twice-daily in 28-day cycles until disease progression or intolerance ; six patients received acalabrutinib 200 mg once-daily and later switched to 100 mg twice-daily .

At a median follow-up of 27.4 months ( range = 4.6-40.7 months ), 72 percent of patients remained on treatment : 50 percent of treatment-naïve ( n = 7 ) and 75 percent of relapsed / refractory patients ( n = 69 ).

“ Treatment discontinuation due to adverse events ( AEs ) was low ,” Dr . Owen noted , at 21 percent ( n = 3 ) and 4 percent

TABLE 3 . Treatment Response

Treatment- Naïve Cohort ( n = 14 )

Relapsed / Refractory Cohort ( n = 92 )

( n = 4 ) in the treatment-naïve and relapsed / refractory cohorts , respectively . Other causes for discontinuation were disease progression ( 0 and 9 [ 10 %]), investigator decision ( 2 [ 14 %] and 4 [ 4 %]), and death ( 1 [ 7 %] and 3 [ 3 %]).

The primary endpoint of ORR ( defined as a minor response or better ) was 93 percent ( n = 13 ) in the treatment-naïve cohort and 94 percent ( n = 86 ) in the relapsed / refractory group . The ORR was consistent across prespecified subgroups , including age ≥65 years ( 93.4 %) and ≥3 prior therapies ( 95.5 %).

Median durations of response , progression-free survival , and overall survival were not reached in either cohort . See TABLE 3 for 24-month survival rates and other efficacy outcomes .

The most common any-grade treatmentrelated AEs were headache ( 39 %), diarrhea ( 31 %), contusion ( 29 %), and dizziness ( 25 %). The most common grade 3 / 4 AEs were neutropenia ( 16 %), pneumonia ( 7 %), anemia ( 5 %), increased alanine transaminase ( 5 %), and hyponatremia ( 5 %).

Three patients reported experiencing atrial fibrillation , including one grade 3 event . More than half of patients ( 56 %) experienced bleeding events , most commonly contusion and epistaxis ; four of these were grade 3 / 4 events , but none led to treatment discontinuation . There were five grade 5 AEs ( pneumonia , glioblastoma multiforme , esophageal carcinoma , myocardial ischemia , and intracranial hematoma ).

Of the nine participants who discontinued acalabrutinib due to AEs ( 3 in the treatment-naïve cohort and 6 in the relapsed / refractory cohort ), three developed a secondary malignancy during treatment .

“ We observed rapid and sustained reductions in immunoglobulin , which was mirrored by substantial and sustained improvements in hemoglobin ,” Dr . Owen added . While he noted that acalabrutinib appears to be “ a highly effective treatment for WM with durable responses and limited toxicity ,” the study ’ s findings are limited by its lack of a comparator arm and the small number of patients in the treatment-naïve cohort . The authors report financial relationships with AstraZeneca , the manufacturer of acalabrutinib .

REFERENCE

Owen R , McCarthy H , Rule S , et al . Acalabrutinib in patients ( pts ) with Waldenström macroglobulinemia ( WM ). Abstract # 7501 . Presented at the 2018 American Society of Clinical Oncology Annual Meeting , June 3 , 2018 ; Chicago , IL .

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