Max Topp, MD, from the University Hospital of Wuerzburg, Germany, presented the interim results in a poster here at the 16th Congress of the European Hematology Association (EHA).
Blinatumomab appears to represent a new treatment option for patients with treatment-refractory ALL, he noted. "This is the first clinical evidence that this technology might provide the fifth pillar of cancer therapy. We are testing it in the most aggressive B-cell malignancy we know," he told Medscape Medical News in an interview.
The primary end point of the single-group, multicenter, exploratory phase 2 trial was the rate of CR or CR+. Secondary end points were toxicity and duration of response."Based on the results from the first 12 patients, there is reasonable hope that this will change the way we think about this disease," said Dr. Topp.
A previous phase 2 trial with blinatumomab, presented at the 2010 American Society of Hematology annual meeting, reported results from ALL patients who showed minimal residual disease (MRD) or leukemic cells in the bone marrow, despite having received chemotherapy. Results of this previous study showed that 80% (16 of 20) achieved MRD-negativity, all within the first treatment cycle. Disease-free survival was 60% after a follow-up of up to 27.5 months.
Dismal Prognosis for Relapsed/Refractory ALL
Blinatumomab is the first of a new class of agents designed to direct cytotoxic T-cells to CD19-expressing cancer cells. CD19 is a protein expressed on the surface of B-cell-derived ALLs and non-Hodgkin's lymphomas.
According to Dr. Topp, patients with refractory ALL have a dismal prognosis. Complete remission rates in this subset range from 17% to 45% with intensive chemotherapy, and treatment-related mortality rates range from 12% to 23%. "Even with the best chemotherapy currently available for these patients, such as FLAG/IDA [fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin], only 30% of patients will go into remission. Remission is then usually only of short duration, with a median of around 6 months," he explained.
In the current study, patients had difficult-to-treat B-precursor ALL, and all had relapsed after induction and consolidation therapy once or twice, or had refractory disease. The majority of patients had undergone allogeneic stem cell transplantation in addition to other chemotherapy.
After receiving blinatumomab, 9 of 12 patients reached the primary end point of CR or CR+; all 9 also reached the secondary end point of becoming MRD-negative or obtained molecular remission. Both CR and MRD were reached within the first cycle in responders, so it is "a precise and quick therapy," said Dr. Topp.
"This is unusual in this particular patient group," he remarked.
"This means there was a reduction in tumor burden of greater than 5 logs. This is very significant because the CR rate means a reduction of 1 log, but molecular remission equates to a reduction of 5 logs of tumor burden," he added.
The duration of response remains unknown in this particular trial, and will be reported at a later date, Dr. Topp noted. However, he cited a study he was involved with that was published online May 16 in the Journal of Clinical Oncology, which investigated the effect of blinatumomab on MRD and duration of response. "We found patients who are still MRD-negative after 2.5 years. Extrapolating from those data to this trial, there may be patients who experience a very similar clinical course," said Dr. Topp.
Very interesting Phase II trial for Pre B ALL which is a very difficult disease to treat.
Tony Talebi, MD