Despite ALL treatment progress, patients still need safer, more effective options
Novel agents have transformed outcomes for patients with relapsed or refractory acute lymphoblastic leukemia (ALL), said Selina Luger, MD, of the University of Pennsylvania, during her SOHO Breakthroughs in Blood Cancers session.
Even with these advances, relapse and treatment-related toxicities remain major challenges, according to Dr. Luger.
Dr. Luger explained that outcomes after transplant continue to vary widely by risk group. In several studies, she noted that “survival was primarily because of nonrelapsed mortality.” In high-risk patients with a donor, two-year mortality reached 36%, compared with 14% in those without a donor and 20% in donor-positive patients with standard-risk disease. She added, “Patients who are MRD negative after induction are less likely to actually need a transplant, but those who are MRD positive are more likely to need a transplant.”
Treating younger patients
“The next real advance that we made in ALL was understanding that we needed to treat younger patients differently,” she said. She pointed to CALGB 10403, where younger adults treated with a pediatric-inspired regimen had far better outcomes than in prior adult trials.
“MRD remains very important,” she said, noting the 85% three-year disease-free survival in patients who were MRD-negative at the end of induction.
Reshaping ALL treatment
“We have an unmet need for therapies that are more effective and less toxic,” she said, describing the transition to the new agents now shaping ALL care.
She highlighted the three therapeutic classes reshaping relapsed or refractory ALL treatment: inotuzumab ozogamicin (Besponsa), a CD22-targeted antibody-drug conjugate; tisagenlecleucel (Kymriah), a CAR T-cell therapy; and blinatumomab (BLINCYTO®), a bispecific T-cell engager.
The pivotal phase 3 INO-VATE study evaluated inotuzumab ozogamicin against the standard intensive therapy in relapsed or refractory B-ALL, which showed higher remission rates than standard chemotherapy. That study showed that the rate of complete remission was higher with inotuzumab ozogamicin.
“The major toxicity, however, was hepatic toxicity, and this led to increased toxicity of transplant when done after inotuzumab, with an increased incidence of veno-occlusive disease,” Dr. Luger said. “We have learned how to manage that more these days by spacing out the time between inotuzumab and transplant, decreasing the total number of cycles and dose, and by also using ursodiol.”
The pivotal ELIANA trial evaluated tisagenlecleucel in patients ≥3 years at screening and ≤21 years at diagnosis. She reported that more than five years of follow-up showed an 82% overall response rate, 49% relapse-free survival, and 55% overall survival in patients, with durable efficacy and no late adverse effects.
“Tisagenlecleucel remains a potentially curative option,” Dr. Luger said.
The other two CAR T-cell therapies she mentioned were brexucabtagene autoleucel and obecabtagene autoleucel, both of which show strong response rates across age groups.
The phase 3 TOWER trial showed that patients treated with blinatumomab had “significantly longer overall survival” compared with standard chemotherapy. Dr. Luger also noted that patients with high tumor burden respond less well, with lower complete remission and MRD response rates.
Dr. Luger also discussed promising chemotherapy-free approaches and reviewed recent ASH and EHA presentations, which included long-term follow-up from CALGB 10403 and updated results from E1910.
SOHO Breakthroughs in Blood Cancers is a one-day virtual event featuring the latest advances in hematologic oncology.
