Incorporation of Antibodies Into the Management of Upfront and Relapsed ALL

At the 2022 Lymphoma, Leukemia & Myeloma Congress in New York, Elias Jabbour, MD, MD Anderson Cancer Center, The University of Texas, Houston, TX, provides an update on the incorporation of antibodies into the management of upfront and relapsed acute lymphoblastic leukemia (ALL).

Transcript:

Hello, good morning. My name is Elias Jabbour, professor of medicine at MD Anderson Cancer Center, Houston, Texas. I'm very happy to be here today to present at the Leukemia, Lymphoma and Myeloma meeting in New York. I'm going to present on the role of immunotherapy and the integration for immune therapy into the frontline, and management of refractory [acute lymphoblastic leukemia] (ALL).

I'm very optimistic, and I think we're living in the best time of my life, because the cure for ALL is happening. We have every tool to cure this disease. We have drugs that are approved for the relapsed refractory setting, now finding their way to the frontline. By that, I mean the immunotherapy, be it the antibody drug conjugate, the bispecific engagers, as well as [chimeric antigen receptor T cells] (CAR T-cells). These options were approved for obstructed disease as a single agent, with improvement of survival compared to patients who received standard of care.

Since then, we’ve developed new protocols to explore these drugs into the frontline and into the rapid setting. In the rapid setting, we know historically that a patient with ALL, when they relapse, that is a death sentence. Today, this patient can have an option for a long-term remission, and I will say cure as well. Not only by using single agent, though I think the approval was important to get this drug into the market, but I think research starts from the approval and onward.

We're exploring a combination of these drugs together, targeting different epitopes, CD3 and CD19, put together to induce the deepest response possible, documented by [minimal residual disease] (MRD) assessment by [next-generation sequencing] (NGS). In our experience, this combination, either concomitant or sequential, led to a response rate of a 90% and immediate overall survival of 17 months, which is amazing compared to, historically, 7 months, with a 5-year survival of 45%.

On top of that, we have the CAR T-cells. With the CAR T-cells, essentially, we harness the immune system of a human being, and we teach these T cells how to act, we send them back to attack the cancer cells, the B cells. Alone, they've shown good activity, but the activity was most highlighted in patients with no disease or minimal disease. Rather than giving these CAR-Ts as 1 option for patients who had failed everything with the bulky disease, today we're exploring a sequential approach for the CAR-Ts, to make sure that we give the CAR-T the best optimal setting, and the early data is showing a potential cure for patient with [certain] diseases. Immunotherapy to induce remission, deep remission, and then consulate with the CAR T-cells. I hope one day, CAR-T will replace [allogeneic stem cell] allo-transplant. Into the frontline, we have made progress, but in-patient with adult patients, survival is still around 60% at 5 years, therefore we need to do better than this.

Since immunotherapy is very effective in the relapse setting, we thought of introducing immunotherapy into the frontline. By doing so, we can deepen the responses, shorten the duration of therapy, and eliminate the intensity of the chemotherapy that can lead to long-term complications and side effects, and eventually [reduce the need for] transplant.

What I want to show at the meeting is, in a [precursor B-lymphoblastic leukemia] pre-BLL, we integrated [blinatumomab and ofatumumab] both into the frontline. In younger patients, we've shown survival at 3 to 4 years is 85%, when historically it has been 50% to 60%. Instead of treatment for 3 years, we shortened it to a year to a year and a half, which is excellent. The results are very promising, with more than 70 patients treated at MD Anderson, and there are similar trials ongoing. In older patients, where the outcome is poor for the patient, we added this immunotherapy component into the treatment. By doing so, where historically survival was a year to year and a half, today we have a 5-year survival of 50% for older patients, which is excellent as well.

The last topic I'd like to highlight today is the Ph-positive ALL (PH+ ALL). We know this to be the worst disease, in terms of response to treatment with chemotherapy and transplant, and today, we're able to treat patients without chemotherapy at all by administering immunotherapy and [tyrosine kinase inhibitors] TKI. One of these examples is blinatumomab and ponatinib. In most patients, deep response is 88%, and survival at 3 or 4 years is 95%, without going for transplant.

The evolution of ALL therapy is happening in our lifetime. The cure is happening, and I think adult ALL will have the same cure as pediatric ALL. In conclusion, we have so many options today. I think they are not competitive, rather complimentary. We can use them in optimal way to improve the outcome of our patients.

Source:

Jabbour, E. Incorporation of Antibodies into the Management of ALL: Upfront and Relapsed Disease. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-22, 2022. New York, NY.