‘The HemOnc Pulse’ Live: What Are the Unanswered Questions in ALL?

Recorded at the first “HemOnc Pulse” annual meeting, this podcast episode features a panel discussion on unanswered questions in acute lymphoblastic leukemia (ALL) with Elias Jabbour, MD, a Professor of Medicine at the University of Texas MD Anderson Cancer Center; Shira Dinner, MD, an Associate Professor of Medicine (Hematology and Oncology) at Northwestern Medicine; Sanam Loghavi, MD, an Associate Professor of Pathology at MD Anderson Cancer Center; and Wendy Stock, MD, Co-Leader of the Clinical and Experimental Therapeutics research program at the University of Chicago Medicine Comprehensive Cancer Center.

The panel first discussed ALL treatment, associated toxicities, and the possibility of a chemotherapy-free approach.

“You can get very deep remissions with a chemotherapy-free approach, but it’s still way too early to say whether long-term survival will be reached,” Dr. Stock began. “The early data are extremely promising for older adults, but we have similar survival rates in younger adults with chemotherapy-intensive regimens. The goal is to reduce that toxicity as we move forward.”

The panel also discussed combinations with antibody drug conjugates, which Dr. Dinner described as the “next step” for patients who are not completely chemotherapy-free.

Dr. Dinner highlighted two studies: the A041703 trial, which evaluated inotuzumab ozogamicin induction followed by blinatumomab consolidation for older adults with newly diagnosed Philadelphia (Ph)-negative, CD22-positive, B-cell ALL; and the ECOG 1910 trial, which showed an overall survival benefit to adding blinatumomab to consolidation chemotherapy in patients with measurable residual disease (MRD) negativity.

She also discussed the toxicities of newer immunotherapies that cause increased lymphoid depletion. “We are seeing some delayed infectious toxicities,” she said. “We need to have longer term follow-up of a lot of these regimens.”

Next, the conversation shifted toward MRD in ALL and the possibility of relapse after MRD negativity.

“If you plan to follow your patient with clonoSEQ MRD, taking a baseline sample is the most important thing to do,” Dr. Loghavi said.

As Dr. Stock explained, clonoSEQ is less predictive for T-ALL.

“The sequencing is complicated,” she said. “It’s early to bank on MRD negativity by clonoSEQ 100% of the time. It’s still disease; it’s just below the level of detection. Sometimes, we see ALL relapse 15 years later.”

Next, the panel further explored unanswered questions in Philadelphia (Ph)-positive and-negative ALL.

As for treatment with tyrosine kinase inhibitors in Ph-positive ALL, many clinicians are opting for ponatinib based on recent data.

“Ponatinib is the most potent and can overcome resistance mutations,” Dr. Dinner explained. “Most of us are reaching for it frontline.”

However, ponatinib has a “significant toxicity profile,” with a 30% risk of cardiovascular events, heart attack, and stroke.

“It’s in the black box warning,” she said. “You can’t ignore that.”

One persistent challenge in Ph-negative ALL is treating older patients, according to Dr. Jabbour.

“We’re doing single-cell sequencing upfront and trying to see if chemotherapy-free will overcome this barrier, but I’m not sure we will,” he said.