Treating Elderly Patients With ALL Remains a Challenge for Oncologists

In an interview with Targeted Oncology, Marlise Luskin, MD, MSCE, discussed the challenges of treating adult and elderly patients with acute lymphoblastic leukemia and where new research in the space is headed.

With a need for new and novel treatment regimens in the acute lymphoblastic leukemia (ALL) space, it has been a challenge for experts to treat patients, especially adult and elderly individuals.

While ALL is a diagnosis seen in pediatric, adult, and elderly patients, unique challenges are present when treating older patients. To explain the issue, Marlise Luskin, MD, MSCE,explained the need for new therapies that may be better tolerated by older patients with ALL during a presentation at the Tenth Annual Meeting of the Society of Hematologic Oncology (SOHO).

While there are problems being faced by experts in this space, new research is evaluating different treatment approaches for patients with ALL. For patients with Philadelphia (pH)-chromosome-positive ALL, trials are evaluating the use of agents such as ponatinib (Iclusig), dasatinib (Spryce), and asciminib (Scemblix).

In the pH-negative space, even more trials are evaluating combinations of inotuzumab (Besponsa), venetoclax (Venclexta), and blinatumomab (Blincyto).

“Older adults with ALL can be treated. Treatment needs to be individualized as not all older adults are the same. There's a huge range of fitness and comorbidities. Older adults should be carefully assessed to understand their performance status, their comorbidities, their goals. Patients can be offered effective treatment to get them into remission, and in many cases, offer them a durable remission,” said Luskin, Dana-Farber Cancer Institute, Boston, MA, in an interview with Targeted OncologyTM.

In the interview, Luskin discusses the challenges of treating adult and elderly patients with ALL and where new research in the space is headed.

Can you just start by discussing the session on acute lymphoblastic leukemia in the elderly?

Luskin: I was fortunate to be invited to speak at the 2022 SOHO annual meeting this year on the challenge of treating acute lymphoblastic leukemia in older adults. ALL is a diagnosis that is rare, but is seen in both children, younger adults, and older adults. Treating older adults with this disease has some unique challenges. Fortunately, there are some developments and improvements in this area.

What are some of the challenges faced when treating adult patients with ALL?

Older adults with ALL in contrast to their younger counterparts have a dual challenge. The first is that they have disease that is typically higher risk or more chemotherapy-resistant, due to features of their disease at diagnosis. They are more likely to have high-risk genetic lesions like TP53, high-risk chromosome abnormalities, and are less likely to have favorable chromosomal abnormalities that are typically more chemosensitive, because they have high-risk disease that doesn't typically respond to our typical conventional chemotherapy agents.

On the flip side, older adults don't tolerate the chemotherapy agents that have been so effective in younger adults and cured those younger adults and children, including steroids, vincristine, anthracyclines, and asparaginase, which is particularly challenging to give in even older children, but certainly in adults and older adults.

What options currently exist for this patient population?

For older adults, treatments for ALL are historically limited. Those poor outcomes led many older adults to be offered either no therapy or minimal therapy and to be advised to pursue palliative care. When you look at registry data, it turns out that until recently, many older adults are not even treated. Our presumption is that many patients after the diagnosis aren't referred to academic centers and aren't even offered treatment based on the poor numbers reflected in historical trials of conventional chemotherapy.

But the landscape for older adults with ALL is starting to change. The treatment options depend on 1 major feature: whether or not there's the Philadelphia chromosome present or not. Patients with the Philadelphia chromosome have the ability to be treated with a tyrosine kinase inhibitor or oral chemotherapy. Those drugs can now effectively get patients into remission combined with either just steroids or minimal chemotherapy. For patients who do not have that Philadelphia chromosome, it has been a little bit more challenging to treat these patients effectively. Now we have examples of several trials that have been designed to introduce novel agents that are currently approved in the relapse setting, bringing those novel agents forward, allowing conventional toxic chemotherapy to be reduced, thereby improving response rates, and making that initial treatment more tolerable. Those approaches are investigational. I encourage all older adults to be referred for clinical trials whenever possible.

What are some ongoing research being examined in this space?

There is lots of interest in this space. We're starting to see momentum and there are a number of exciting clinical trials happening in the [United States] and around the world. I will be excited to see that that research matures over the next few years. For Philadelphia chromosome-positive ALL, there are trials exploring different approaches to picking the tyrosine kinase inhibitor with oral chemotherapy, there are trials being run primarily out of The University of Texas MD Anderson Cancer Center looking at ponatinib. This is for patients of all ages, but it is interesting to see how our older patients [will do].

There's a trial being led by myself, a multisite phase 1 trial [NCT03595917], at Dana Farber Cancer Institute and some other institutions looking at combining dasatinib and asciminib, another dual TKI inhibition for pH-positive ALL. In the pH-negative space, there are a number of trials combining either inotuzumab, venetoclax, and blinatumomab into induction and consolidation programs for older adults with ALL.

What factors would kind of influence your choices when individualizing treatment for patients?

What factors that I look at would be, in addition to the age of the patient, their physiologic age, how active they are, frailty, and there are formal frailty assessments developed by colleagues in geriatric oncology and even assessed by geriatricians when possible. There are other ways to assess that in terms of understanding the daily life of the patient. Then understanding how their other medical problems affect their health, their cardiac pulmonary kidneys, know what their other comorbidities are, and then selecting treatments based on their fitness, their comorbidities, the patient's goal, how aggressive they want to be, what their tolerance for risk is, and then coming up with a treatment plan with the patient, their family, and the care team that meets everybody's goals and needs.

What are the key takeaways experts should know when treating older patients with ALL?

Older adults with ALL can be treated. Treatment needs to be individualized as not all older adults are the same. There's a huge range of fitness and comorbidities. Older adults should be carefully assessed to understand their performance status, their comorbidities, their goals. Patients can be offered effective treatment to get them into remission, and in many cases, offer them a durable remission. I encourage whatever is possible to offer these patients a consultation at an academic center where there may be a clinical trial or expertise about how to adjust chemotherapy doses. Incorporate novel agents, again, ideally on a trial, but how to best approach the field is rapidly changing. We certainly want to offer those improvements to as many older adults as possible.