Recent Updates in Diagnosing and Treating Acute Lymphoblastic Leukemia

Kjeld Schmiegelow, MD

With recent and increasing data in the acute lymphoblastic leukemia (ALL) space, treatments are moving away from traditional chemotherapy and transplantation and into the direction of targeted therapies to improve survival rates.

Many promising therapies have gained approvals for the treatment of patients with refractory ALL, including chimeric antigen receptor (CAR) T cells, blinatumomab (Blincyto), inotuzumab ozogamicin (Besponsa), and the tyrosine kinase inhibitor (TKI) ponatinib (Iclusig).

As more is being learned in this setting, some agents are being combined in earlier settings, and demonstrating promising response rates as well as overall survival findings.

During a recent session at the 10th Annual Meeting of the Society of Hematologic Oncology (SOHO 2022) that focused on the current landscape for ALL, experts, including Kjeld Schmiegelow, MD addressed the current treatment options available for patients in this space and in their respective cancer settings. This session provided experts with a place to look forward and learn about the emerging approaches on the horizon.

“I think that we will continue to improve outcomes for children and for adults as we have over the last 1-2 decades. We’re still constantly getting better and better,” said Schmiegelow, MD, Department of Pediatrics and Adolescent Medicine, The Juliane Marie Centre, Rigshospitalet at Copenhagen University Hospital, in an interview with Targeted OncologyTM.

In the interview, Schmiegelow provided a deep dive into his SOHO 2022 presentation as well as the other ALL discussions presented during the session.

Targeted Oncology: Can you give a brief overview of the session you were a part of this morning?

Schmiegelow: We had 3 speakers. I had a talk on how we have succeeded in integrating a standard diagnostic and treatment platform for both children and adults. This has taught us a lot because we can combine treatment responses and toxicity profiles across the age groups to develop a deeper understanding, not just on how we can improve the cure rate for adults, but also, for adolescents.

Then Selina Luger, MD, had a talk on the value of minimal residual disease in ALL. [She discussed] how do we fix it and get better diagnostic approaches to minimal residual disease so we can measure that at a deeper level. On the other hand, it's not necessarily required to have very deep measurements for all patient subsets. We could say that for some patients, it's very relevant to capture if they do not respond fully and then allocate them to more intensive therapy. For others MRD can be used to de-escalate the treatment, which is a major issue for not only children but also for the good responding adults where the cure rates may be 90% or more.

But there are some settings where we know that cure rates with chemotherapy are unsatisfactory. Here targeted immunotherapies like CAR T-cell therapy are highly relevant.

Accordingly, Nitin Jain gave a talk on approaches to develop novel strategies for CAR T-cell therapies which is of course a revolution of anticancer therapies. We know it is highly effective, but some patients may fail. He highlighted that we need better strategies to serve the CAR T-cell therapy and the major challenge we have had has been it is quite time consuming to develop the CAR T for the individual patient, and provided data on off the shelf, allogeneic CAR T that you can then allocate to individual patients in a much more rapid way.

What questions need to be answered in the current ALL space?

One question is, can we still improve the treatment based on the traditional drugs in combination with the innovative updates that we have had in the past decades? Can they provide even better outcomes? There's a number of things that can emerge in the therapeutic landscape. Measuring the activity, or the concentration of individual drugs may give us a wave on how to improve therapies. We're still on track to getting better use of the traditional drugs. We are slightly behind when it comes to treating adult patients. The other track are novel agents which have been providing profound effects for patients with leukemia.

The novel and even targeted therapies are but at their very early stage. But I think that we will continue to improve outcomes for children and for adults as we have over the last 1-2 decades. This includes both higher cure rates and in parallel de-escalating therapy to avoid toxicities.

What are the key takeaways you hope people get from your discussion at SOHO?

I think the key issue is that it's feasible to treat children and adults at least up to the age of 45 years with the same strategies. It is not just a benefit for adults, but adolescents also benefit from these efforts as their outcomes are relatively similar. By providing volume to this topic, you can learn even more.

Since adults with ALL have had inferior outcomes, novel drugs are being primarily tested in these age groups. Accordingly, we as pediatricians can learn from these experiences in poor risk patients.

What unmet needs still exist in this space?

We want to cure every patient without toxicity and that's the unmet need. Getting down to a few months of therapy may be achievable for the best responding patients. If we go back to the 60’s and 70's, we were in fact able to cure some patients with very little therapy. That is an unmet need, to be able to identify early on who needs intensified and long-lasting therapy and for whom we can potentially stop therapy after a few months to avoid toxicities and reduce costs.