SAN FRANCISCO – Positive results with blinatumomab and inotuzumab ozogamicin in the relapsed/refractory setting have prompted trials of these immunotherapies in newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL).
Dr. Jae Park
Blinatumomab and inotuzumab have been shown to improve overall survival, compared with chemotherapy, in patients with relapsed/refractory B-ALL. However, most adults with relapsed/refractory B-ALL still die, so the initial therapy patients receive is “critical,” according to Jae Park, MD, of Memorial Sloan Kettering Cancer Center in New York.
“Ideally, we do not want to deal with the relapse,” Dr. Park said. “It’s better to cure the disease the first time ... which is the reason clinical trials are incorporating these agents earlier.”
Dr. Park discussed these points at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress.
Blinatumomab
Dr. Park cited the phase 3 TOWER trial, which showed that blinatumomab produced better response rates and overall survival compared with standard chemotherapy. The trial enrolled 405 patients with Ph-negative relapsed/refractory B-ALL who were randomized to blinatumomab (n = 271) or chemotherapy (n = 134).
The rate of complete response (CR) with full, partial, or incomplete hematologic recovery was 44% with blinatumomab and 25% with chemotherapy (P less than .001). The median overall survival was 7.7 months and 4.0 months, respectively (P = .01; N Engl J Med 2017; 376:836-47).
Based on these data, researchers decided to test blinatumomab in newly diagnosed, elderly patients (65 years and older) with Ph-negative B-ALL in the phase 2 SWOG 1318 study. The study enrolled 31 patients, and 29 were eligible. Their median age at baseline was 75 years (range 66‐84 years).
The patients received blinatumomab for two to five cycles, followed by 18 months of maintenance with prednisone, vincristine, 6-mercaptopurine, and methotrexate. One patient went on to transplant.
In all, 66% of patients achieved a CR or CR with incomplete count recovery. The estimated overall survival was 79% at 6 months and 65% at 1 year. These results were presented at the 2018 annual meeting of the American Society of Hematology (Blood. 2018;132:33).
Another study of blinatumomab as frontline treatment is the ECOG-E1910 trial. In this phase 3 study, researchers are testing chemotherapy, with or without blinatumomab, in adults (aged 30-70 years) with newly diagnosed, BCR-ABL-negative B-ALL. Results from this study are not yet available.
Inotuzumab ozogamicin
Dr. Park also discussed the INOVATE trial, in which inotuzumab ozogamicin bested standard chemotherapy. The trial enrolled patients with Ph-positive or negative, relapsed/refractory B-ALL.
The patients were randomized to inotuzumab (n = 141) or investigator’s choice of chemotherapy (n = 138). Some patients, 41% in the inotuzumab arm and 11% in the chemotherapy arm, went on to transplant.
The CR rate was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P less than .001). The median progression-free survival was 5 months and 1.8 months, respectively (P less than .001). The median overall survival was 7.7 months and 6.7 months, respectively (P = .04; N Engl J Med 2016; 375:740-53).
Based on these results, researchers are testing inotuzumab as frontline therapy in young adults (aged 18-39 years) with CD22-positive, Ph-negative B-ALL. In the phase 3 A041501 trial, patients are receiving inotuzumab after the first and second courses of treatment with the CALGB 10403 chemotherapy regimen. Results from this trial are not yet available.
Dr. Park reported relationships with Allogene Therapeutics, Amgen, AstraZeneca, Incyte, Kite Pharma, Novartis, and Takeda.