ERY001 yields positive outcomes for treatment of relapsed ALL

CHICAGO – ERY001 demonstrated efficacy as an alternative treatment option to asparaginase for patients with relapsed acute lymphoblastic leukemia, according to a randomized phase 3 study presented at the ASCO Annual Meeting.

Perspective from Guido Marcucci, MD

Asparaginase is frequently used in the treatment of ALL; however, toxicities — including hypersensitivity — limit its efficacy, according to study background. Patients with a clinical allergy may have antibodies that inactivate asparaginase. Further, these patients also are at risk for asparaginase neutralization without any clinical signs of inactivation.

“It is important to develop a means of administering asparaginase [to patients with hypersensitivity],” Yves Bertrand, MD, of the department of pediatric hematology at Claude Bernard University in Lyon, France, said during a presentation. “We used an innovative process of encapsulation, taking red blood cells and putting them in the hypertonic region, opening the walls of the red blood cells and allowing the asparaginase to enter.”

Due to the protective barrier of the erythrocyte membrane, erythrocyte encapsulated l-asparaginase (ERY001, ERYTECH Pharma) improves pharmacokinetics, boosts tolerability and preserves circulating asparaginase activity, according to the researchers.

Bertrand and colleagues enrolled 80 pediatric and adult patients (range, 1-55 years) with relapsed ALL in an open, randomized, international phase 3 study. Researchers designed the study to detect threefold differences in the incidence of allergic reactions between treatments.

Researchers randomly assigned patients to ERY001 (150 IU/kg; n = 26) native l-asparaginase (10,000 IU/m²; n = 28), or ERY001-exp (prior allergy; n = 26).

Duration of asparaginase activity greater than 100 IU/L and the incidence of asparaginase hypersensitivity during induction served as the primary endpoints. Complete remission, minimal residual disease, EFS and OS served as secondary endpoints.

Researchers noted that non-allergic patients in the ERY001 arm experienced a significant reduction in the rate of asparaginase hypersensitivity compared with patients who received l-asparaginase (0% vs. 43%; P < .001). Further, patients assigned ERY001 demonstrated a greater duration of asparaginase activity compared with patients assigned l-asparaginase (21 ± 5 days vs. 9 ± 8 days; P < .001).

The complete response rate was 65% (95% CI, 51.6-89.9) in patients who received ERY001 compared with 39% (95% CI, 23.3-63.1) among patients who received l-asparaginase (P = .026). Sixty-five percent of patients assigned ERY001 successfully underwent allograft treatment compared with 46% of patients assigned l-asparaginase.

Thirty-five percent of patients in the ERY001 arm achieved minimal residual disease (< 10^-3 in F1-F2/VANDA), compared with 25% of patients in the l-asparaginase arm.

Further, a greater proportion of patients in the ERY001 arm achieved 12-month EFS compared with patients in the l-asparaginase arm (65% vs. 49%).

“ERY001 assisted asparaginase activity and displayed superiority to treatment with native asparaginase,” Bertrand said. “The prolonged asparaginase activity was associated with improvement … The treatment was well-tolerated, and we are actually using [ERY001] in patients with a previous allergy to other forms of asparaginase.” – by Cameron Kelsall

Reference:

Bertrand Y, et al. Abstract 7004. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Disclosure: Bertrand reports honoraria from and a consulting role with ERYTECH Pharma. Please see the abstract for a list of all other researchers’ relevant financial disclosures.

Perspective

Guido Marcucci, MD

Asparaginase is an important component of the chemotherapy regimen for acute lymphoblastic leukemia, but the limitation for the use of this drug has been allergies and toxicities in certain patients. Better formulation and ability to deliver the drug in the safest way has always been a goal. Finally, we are seeing that we can encapsulate the formulation of the drug and offer an excellent safety profile. Further, we may have available an encapsulated formulation of the drug that offers an excellent safety profile and increased clinical activity in relapsed ALL, which has notoriously been very difficult to treat.

Guido Marcucci, MD

City of Hope

Disclosures: Marcucci reports no relevant financial disclosures.