Drs. Hagop Kantarjian and Rob Pieters will debate whether ALL is ready to move away from chemotherapy. SOHO Insider editor, Elias Jabbour, MD, explores what the evidence shows in this preview.
The debate over whether chemotherapy is still needed for patients with acute lymphoblastic leukemia reflects one of the most important questions facing the field today. While immunotherapy has transformed treatment and made less chemotherapy-intensive approaches increasingly feasible, questions remain about which patients can safely avoid chemotherapy altogether. I believe the field is moving in that direction, but additional evidence is needed before chemotherapy-free regimens can be broadly adopted.
It is a very exciting time in ALL; the advances are immense. The next question is, do we still need chemotherapy? Historically, patients have required three years of treatment, though that requires adherence to optimize outcomes.
We have had immunotherapy available since 2014, and the results to date show better outcomes than chemotherapy alone. The question we are now facing is whether we can safely replace chemotherapy with immunotherapy and move away from the intensity and duration of treatment.
The randomized E1910 trial showed that adding blinatumomab to consolidation chemotherapy improves outcomes, though this regimen still includes chemotherapy. At MD Anderson, we conducted a trial using less chemotherapy by substituting immunotherapy, and we have shown that this approach is safe, effective, and improves outcomes.
I believe there is a path toward moving away from chemotherapy and more toward immunotherapy, although additional trials are still needed to confirm this direction.
In Philadelphia chromosome-positive ALL, we have shown that treatment with blinatumomab and ponatinib can eliminate the need for chemotherapy while improving outcomes.
That said, I still believe there is a role for chemotherapy and chimeric antigen receptor T-cell therapy in certain patients, such as those with high white blood cell counts at high risk of central nervous system disease, where chemotherapy is needed for central nervous system penetration.
Can we mitigate this issue with chimeric antigen receptor T-cell therapy? It is very possible. Frontline CAR T-cell therapy trials are ongoing to address this risk and further improve outcomes. We have launched a trial evaluating mini-hyper-CVD plus inotuzumab ozogamicin followed by CAR T-cell therapy, with the goal of delivering seven to eight months of treatment and curing ALL.
Will that become a reality? Not today, but confirmatory trials are needed to prove this point. I believe there is a way to move away from chemotherapy, and ongoing trials will determine whether this approach can become the new standard.
Elias Jabbour, MD, is an editor at SOHO Insider, and a professor in the Department of Leukemia in the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center.
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