April 6, 2018 : Episode 1

FDA Approval in ALL, Priority Review in Hairy Cell Leukemia, European Approval in Myeloma, and More



An FDA approval in acute lymphoblastic leukemia, a priority review in hairy cell leukemia, a European approval in multiple myeloma, a Japanese expedited review in gastric cancer, and encouraging phase II findings in an ovarian cancer trial.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has granted an accelerated approval to blinatumomab for the treatment of adult and pediatric patients with B-cell precursor acute lymphoblastic leukemia who are in remission but still have minimal residual disease. This marks the first approval for patients with MRD-positive ALL.

The approval follows an 8 to 4 vote in favor of the indication from the FDA’s Oncologic Drugs Advisory Committee. The panel based its recommendation on results of the phase II BLAST study, in which blinatumomab induced a nearly 80% complete MRD response rate in patients with MRD-positive ALL in hematologic complete remission.

In the study, of 116 patients who received at least one dose of blinatumomab, the FDA identified 87 in CR with hematologic recovery and baseline MRD of more than 0.1%, including 61 patients in CR1, 25 in CR2 and 1 in CR3. A total 69 patients achieved a complete MRD response within the first cycle.

Additional findings showed that the 18-month relapse-free survival rate was 56%, and the estimated median RFS was 22.3 months. The estimated median RFS time in first CR at the time of treatment with blinatumomab was 25.6 months, median RFS time in the second or third CR was 11.0. The RFS time was numerically longer for patients in CR1 than for those in the second or third CR.

Moreover, the estimated median RFS time was 23.6 months for patients with a complete MRD response and 5.7 months for the MRD-nonresponders.

The FDA briefing document for the ODAC meeting noted that the safety profile for blinatumomab in this setting was similar to what has been demonstrated with the treatment in patients with relapsed/refractory ALL.


The FDA has granted a priority review to a biologics license application for moxetumomab pasudotox as a potential treatment for adult patients with hairy cell leukemia who have received at least 2 prior lines of therapy.

The application is based on findings from the phase III 1053 trial, which met its primary endpoint of durable complete response in adult patients with relapsed/refractory HCL. Findings from this study will be presented at an upcoming medical meeting.

Moxetumomab pasudotox is as an investigational anti-CD22 recombinant immunotoxin.

There is currently no established standard of care and few available therapies for patients with relapsed or refractory HCL.

Under the Prescription Drug User Fee Act, the FDA will make a decision on the approval in the third quarter of 2018.


In multiple myeloma, the European Commission has approved denosumab for the prevention of skeletal-related events in adult patients.

The expanded indication was based on data from the phase III 482 study, in which denosumab demonstrated noninferiority to zoledronic acid at delaying the time to the first SRE in patients with multiple myeloma.

The median time to first on-study SRE was similar between the denosumab arm at 22.8 months and 24.0 months in the zoledronic acid group. The multiple events analysis of time to first and subsequent SREs also did not show superiority for denosumab.

The approval follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use, and applies to all 28 countries in the European Union.

Based on the 482 study findings, the FDA approved denosumab in this setting in January 2018.


A Sakigake designation has been granted to trastuzumab deruxtecan, also known as DS-8201, for the treatment of patients with HER2-positive gastric cancer that is refractory to trastuzumab.

The designation is based on first-in-human findings for the novel investigational HER2-targeting antibody-drug conjugate, in which the confirmed objective response rate was 45.5% and the disease control rate was 81.8% among 44 evaluable patients with heavily pretreated HER2-expressing gastric cancer. Among 23 patients who received prior irinotecan treatment, the ORR and DCR were 43.5% and 82.6%, respectively.

Results also showed that the median progression-free survival was 5.8 months in the overall evaluable population and 4.1 months in those previously treated with irinotecan. The median duration of response was 7.0 months in the efficacy evaluable patients, and 6.9 months in those with prior irinotecan exposure. The vast majority of patients experienced tumor shrinkage.

The designation from the Japanese Ministry of Health, Labor and Welfare gives trastuzumab deruxtecan prioritized consultation, a dedicated review system to support the development and review process, and a reduced review time from the normal 12 months to 6 months.


In ovarian cancer, preliminary data from a small trial showed that the frontline combination of platinum-containing chemotherapy plus the anti-PD-1 agent pembrolizumab, followed by pembrolizumab maintenance, appeared feasible and safe for patients with advanced epithelial disease.

In the investigator-initiated study, the first-line chemotherapy consisted of carboplatin and a taxane. Patients with any postoperative residual disease status were eligible for enrollment.

Of the 10 patients on the study, 6 exhibited no evidence of disease during follow-up for as long as 14 months after debulking surgery, including 1 patient who had suboptimal surgical results.

Additionally, no new or unexpected adverse events occurred, and no patients developed immune-related adverse events during maintenance therapy. The efficacy of the treatment strategy remains to be determined.

The rationale for the combination regimen stems from the well-established association between extent of residual disease and long-term outcomes in ovarian cancer. Patients who attain optimal microscopic disease status have better long-term outcomes compared with patients who have optimal macroscopic or suboptimal disease status.


This week, we sat down with Dr William Wierda, of The University of Texas MD Anderson Cancer Center, to discuss prognostic factors in chronic lymphocytic leukemia.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.

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