The days of using chemotherapy to treat Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) may be numbered.
In a phase 2 trial, up-front chemo-free induction/consolidation with the tyrosine kinase inhibitor dasatinib (Sprycel) and the bispecific T-cell engager antibody blinatumomab (Blincyto) yielded high rates of molecular response, “impressive” survival at 18 months, and few toxic effects of grade 3 or higher, say researchers.
With this approach, “60% of adult Ph+ ALL patients, of all ages, can obtain a molecular response, and this percent can increase further with more cycles of blinatumomab,” lead researcher Robin Foà, MD, from Sapienza University of Rome, in Italy, told Medscape Medical News.
“The rates of disease-free survival and overall survival at 18 months are highly favorable, and the protocol is associated with limited toxicity,” Foà added.
“I see this chemo-free approach becoming a realistic approach for a substantial proportion of adult Ph+ ALL patients, particularly for the older patients, keeping in mind that the incidence of Ph+ ALL increases with age,” Foà said.
The results of the study were published October 22 in The New England Journal of Medicine.
“Innovative” and “Highly Successful”
This “innovative” chemo-free approach proved “highly successful” with “surprisingly” few toxic effects, writes Dieter Hoelzer, MD, PhD, University of Frankfurt, Germany, in a linked editorial.
The Italian GIMEMA LAL2116 D-ALBA trial enrolled 63 adults (median age, 54 years; range, 24 – 82 years) with newly diagnosed Ph+ ALL. All patients received a glucocorticoid for 31 days beginning 7 days before starting treatment with dasatinib.
Dasatinib (140 mg once daily) induction therapy lasted 85 days. All patients who completed the induction phase received blinatumomab (28 μg/d) consolidation therapy. Dexamethasone (20 mg) was administered before each blinatumomab cycle. To prevent central nervous system adverse events, levetiracetam (500 mg twice daily) was administered.
All but two patients completed dasatinib induction. One was a 73-year-old woman who withdrew from the trial because of toxic effects after 10 days of dasatinib treatment. She later died of pneumonia. The other was an 82-year-old woman who had a complete hematologic response but left the trial because of pneumonia and pneumonitis.
At the end of the induction phase, 98% of the patients (62 of 63) had a complete hematologic response, including the patient with a complete hematologic response who withdrew; 29% (17 of 59 patients) had a molecular response.
Of the 61 patients who completed the induction phase, 58 received one cycle of blinatumomab, 56 received two cycles, 45 received three cycles, 37 received four cycles, and 29 received five cycles. At the end of the second blinatumomab cycle, 60% of the patients (33 of 55 patients) had a molecular response.
The percentage of patients with a molecular response increased further after receiving additional cycles of blinatumomab — to 70% (28 of 40 patients) after the third cycle, 81% (29 of 36 patients) after the fourth cycle, and 72% (21 of 29 patients) after the fifth cycle.
At a median follow-up of 18 months, overall survival was 95%, and