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Targeted therapies effective for acute lymphoblastic leukemia
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NEW YORK — Targeted therapies such as inotuzumab and blinatumomab appear associated with high rates of complete molecular remission in patients with acute lymphoblastic leukemia, according to a presenter at HemOnc Today New York.
These agents also appear well tolerated.
“Novel antibodies have really shown encouraging results in relapsed/refractory ALL and are starting to be incorporated in the upfront setting,” Anjali S. Advani, MD, director of the impatient leukemia unit and associate professor at Cleveland Clinic, said during her presentation.
As HemOnc Today previously reported, the FDA last year approved inotuzumab ozogamicin (Besponsa; Wyeth Pharmaceuticals, Pfizer) — an antibody-drug conjugate comprised of a monoclonal antibody that targets CD22 linked to a cytotoxic agent — for the treatment of adults with relapsed or refractory B-cell precursor ALL.
The FDA based this approval on results from the INO-VATE ALL study, which included 326 patients with relapsed or refractory ALL who were randomly assigned 1:1 to standard chemotherapy or inotuzumab ozogamicin.
Results showed a higher percentage of patients treated with inotuzumab ozogamicin achieved complete remission (80.7% vs. 33.3%).
“If you look at patients treated with inotuzumab vs. standard of care, the remission rate was clearly higher,” Advani said. “In those patients achieving response, the rate of complete molecular remission was extremely high.”
Inotuzumab ozogamicin generally was well tolerated, though patients who received the agent demonstrated increased risk for veno-occlusive disease than those assigned chemotherapy (11% vs. 1%).
“This is important to keep in mind when you’re trying to make a treatment decision because most of these patients are trying to get to transplant,” Advani said. “Risk for veno-occlusive disease did seem to correlate with patients who received a dual alkylator regimen for transplant. Going forward, trying to reduce the risk for veno-occlusive disease is important.”
Another targeted therapy, blinatumomab (Blincyto, Amgen) — a CD19–directed CD3 bispecific T-cell engager immunotherapy — is approved for the treatment of treatment of children and adults with relapsed or refractory B-cell precursor ALL.
In an initial study of 20 patients with B-precursor ALL treated with blinatumomab, 80% of patients achieved molecular complete remission. All responses occurred within the first cycle of treatment.
In a phase 2 trial of 189 adults with relapsed or refractory B-precursor ALL, results showed response rates of 43% for patients treated with blinatumomab.
The most common toxicities associated with blinatumomab included pyrexia (60%), headache (34%), febrile neutropenia (28%) and peripheral edema (26%).
“Most of the neurologic events were grade 1 or grade 2,” Advani said. “It is something we have to be aware of and we do need to deal with, but the risk of grade 3 or higher toxicities, either neurologic or cytokine release syndrome, tends to be lower and does seem to correlate with tumor burden.”
There are no targeted therapies approved for frontline treatment of ALL.
“Where we’re going forward is trying to incorporate these agents, such as blinatumomab and inotuzumab, in the upfront setting in newly diagnosed ALL,” Advani said.
“An improved understanding of disease biology is really going to be critical to develop further therapies,” she added. “We have now identified these Ph-like signature, but I’m sure there are many other subsets of ALL, and I think much more work needs to be done.” – by Cassie Homer
Disclosure: Advani reports a consultant role with Pfizer, as well as contracted research from Amgen and Regeneron.