On Location Conference Coverage
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Moxetumomab Pasudotox : An Alternative to Chemotherapy in Hairy Cell Leukemia
In a pivotal phase III clinical trial of moxetumomab pasudotox in patients with relapsed / refractory hairy cell leukemia ( HCL ), three-quarters of participants responded to treatment . Forty-one percent of those were complete responses ( CRs ), and many complete responders also had undetectable levels of minimal residual disease ( MRD ), according to lead author Robert J . Kreitman , MD .
“ Moxetumomab pasudotox is a nonchemotherapeutic agent that has the potential to become a standard of care for patients with relapsed / refractory HCL ,” Dr . Kreitman , of the National Cancer Institute ’ s Center for Cancer Research , said during his presentation of the results at the 2018 ASCO Annual Meeting .
The trial included 80 patients ( median age = 60 years ; range = 34-84 years ) who had received at least two prior systemic therapies , including at least one purine nucleoside analog . Participants were excluded if they had poor hepatic , renal , or pulmonary function ; received therapy within three weeks of enrollment ; or previously received an immunotoxin .
The median number of prior systemic therapies was three ( range = 2-11 ), and 39 patients ( 49 %) received at least four prior lines of therapy . “ This was a heavily pretreated population , and the HCL involvement in bone marrow was high , at a median of 85 percent [ range = 0-100 %],” Dr . Kreitman noted .
Moxetumomab pasudotox 40 µ g / kg was administered intravenously on days 1 , 3 , and 5 of 28-day cycles , for up to six cycles . Participants were treated until disease progression or unacceptable toxicity .
Attendees browse posters at the 2018 ASCO Annual Meeting .
If patients were found to have MRD-negative status within six cycles of treatment , they had the option to discontinue .
The study ’ s primary endpoint was durable CR followed by hematologic remission ( defined as resolution of cytopenias without transfusions or growth factors ) that lasted for longer than 180 days .
As of May 24 , 2017 ( data cutoff ), 50 participants ( 62.5 %) had completed six cycles of treatment and were still being followed .
Of the 30 remaining patients , reasons for treatment discontinuation included : MRD-negativity within six cycles ( n = 12 ; 15 %), adverse events ( AEs ; n = 12 ; 15 %), lack of benefit ( n = 3 ; 3.8 %), disease progression ( n = 2 ; 2.5 %), and death ( n = 1 ; 1.3 %).
At a median follow-up of 16.7 months ( range not provided ), the objective response rate ( ORR ) was 75 percent , including :
• 64 patients with hematologic remission ( 80 %)
• 33 patients with CR ( 41 %)
• 24 patients with CR lasting > 180 days ( 30 %)
Dr . Kreitman noted that the 64 patients who achieved hematologic remission did so rapidly , at a median of 1.1 months ( range not reported ). The duration of both objective response and median progression-free survival were not reached .
As suggested by the 15 patients who discontinued treatment after achieving
Axicabtagene Ciloleucel Moves to Acute Lymphocytic Leukemia
Axicabtagene ciloleucel , which in October 2017 became the first chimeric antigen receptor ( CAR ) T-cell therapy approved for the treatment of B-cell lymphoma , showed “ promising efficacy ” in patients with relapsed / refractory , CD19-positive acute lymphocytic leukemia ( ALL ), according to results from the ZUMA-3 trial .
The results were seen independent of prior exposure to blinatumomab , a CD19 / CD3 bispecific T-cell engager that is considered a standard of care for patients with relapsed / refractory ALL , lead author and presenter Bijal D . Shah , MD , from the Moffitt Cancer Center in Tampa , Florida , noted . These findings update ZUMA-3 data that were presented at the 2017 ASH Annual Meeting , in which 71 percent of patients treated with the anti-CD19 CAR T-cell therapy experienced a complete response ( CR ) or CR with incomplete hematologic recovery ( CRi ).
“ An important question emerged during the conduct of [ ZUMA-3 ]: How would prior blinatumomab influence T-cell quality , T-cell function , and – secondarily – safety and efficacy with this product ?” Dr . Shah said . “ We don ’ t know the mechanisms of resistance to blinatumomab , but we can infer that perhaps these patients might be at higher risk of treatment failure .”
To answer this question , the investigators evaluated the safety and efficacy of axicabtagene ciloleucel among 23 adults : 11 patients had prior blinatumomab exposure , and 12 were blinatumomab-naïve . The authors observed that patients who received blinatumomab appeared to have worse performance status ( Eastern Cooperative Oncology Group stage 0 = 27 % vs . 44 %), were more heavily pre-treated ( relapsed / refractory to second-line treatment = 55 % vs . 28 %) and had a higher blast cell burden at enrollment ( median blasts at screening = 85 vs . 66 ; p values not reported ).
As of July 31 , 2017 ( data cutoff ) and a median follow-up of 2.7 months ( range = 0-10.6 months ), 23 patients were evaluable for safety and 18 were evaluable for efficacy .
Following low-dose conditioning chemotherapy ( fludarabine 25 mg / m 2 and cyclophosphamide 900 mg / m 2 ), patients received axicabtagene
MRD-negativity early , treatment with moxetumomab pasudotox was associated with clearance of HCL burden : 27 of the 33 ( 82 %) patients in CR also had undetectable MRD .
The most common treatment-related AEs included : nausea ( 28 %), peripheral edema ( 26 %), headache ( 21 %), and pyrexia ( 20 %). Treatment-related AEs that led to moxetumomab pasudotox discontinuation were hemolytic uremic syndrome ( n = 4 ; 5 %), capillary leak syndrome ( n = 2 ; 3 %), and increased blood creatinine ( n = 2 ; 3 %). Both hemolytic uremic syndrome and capillary leak syndrome were “ manageable and reversible with close monitoring and best supportive care ,” the authors reported .
Three patients died during study follow-up , but none of the deaths were considered related to treatment .
Based on results from the phase I trial , the U . S . Food and Drug Administration granted moxetumomab pasudotox priority review for the treatment of adults with HCL who have received at least two prior lines of therapy in April 2018 .
The findings of this trial are limited by its single-arm design , small patient population , and limited follow-up .
The authors report financial relationships with AstraZeneca and MedImmune , the manufacturer of moxetumomab pasudotox .
REFERENCE
Kreitman RJ , Dearden C , Zinzani PL , et al . Moxetumomab pasudotox in heavily pretreated patients with relapsed / refractory hairy cell leukemia : Results of a pivotal international study . Abstract # 7004 . Presented at the 2018 ASCO Annual Meeting , June 2 , 2018 ; Chicago , IL .
26 ASH Clinical News July 2018 Bonus Mid-Year Edition