Elias Jabbour, MD
The treatment paradigm of acute lymphoblastic leukemia (ALL) has evolved with a number of advances over recent years, such as TKIs, antibody-drug conjugates, bispecific T-cell engager (BiTE) antibodies, and chimeric antigen receptor (CAR) T-cell therapy.
For example, the FDA granted an accelerated approval to the bispecific antibody blinatumomab (Blincyto) for the treatment of adult and pediatric patients with B-cell precursor acute ALL who are in remission, but still have minimal residual disease (MRD) in March 2018. This follows its prior approval as a therapy for adult and pediatric patients with relapsed/refractory B-cell precursor ALL.
“ALL is a rare disease; in a year, we see around 5000 cases,” said Elias Jabbour, MD, professor of medicine at The University of Texas MD Anderson Cancer Center. “It’s [important to] refer your patients to clinical trials so we can work together.”
Ongoing research with blinatumomab is focusing on the agent in combination. One phase II trial is exploring hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) in sequential combination with blinatumomab as a frontline treatment for adults with B-cell lineage ALL (NCT02877303).
Additionally, an ongoing phase I/II trial is evaluating inotuzumab ozogamicin (Besponsa) plus blinatumomab and combination chemotherapy for patients ≥60 years of age with treatment-naïve ALL (NCT01371630).
However, patients with Philadelphia chromosome (Ph)–positive disease require different treatment options, explained Jabbour. In addition, patients with Ph-like ALL also require alternative therapies. This subgroup is characterized by a similar genetic profile to Ph-positive ALL, but they do not share the BCR-ABL1
fusion. Also, in Ph-like disease, TKIs could be effective.
In an interview with OncLive
during the 23rd International Congress on Hematologic Malignancies: Focus on Leukemias, Lymphomas, and Myeloma®
, Jabbour discussed the treatment options for patients with ALL across these various subgroups.
OncLive: What are the current treatment options for patients with ALL?
: In ALL, we are seeing a lot of evolution in a lot of great things. The major advances have been TKIs, monoclonal antibodies, BiTE engagers, and CAR T cells. In Ph-positive ALL, TKI added to chemotherapy showed that [it has a] great benefit in improving survival. Today, survival at 5 years is approaching 70%, and the idea that [stem cell] transplant is the only way to cure these patients is really a matter of debate. A patient can be cured without transplantation, which is really good. In this disease, we are moving away from chemotherapy by adding new drugs—such as a combination of blinatumomab with ponatinib (Iclusig), for example. It’s a chemotherapy-free regimen for these patients.
In relapsed disease, we have seen approvals of 3 drugs over the last few years. Inotuzumab ozogamicin, which is an anti-CD22 conjugate to calicheamicin; blinatumomab, which is a BiTE [antibody]; and CD19-targeted CAR T-cell therapies, as well. These drugs have shown great results in the lab setting with improvement in survival and higher response rate. Although it’s not what we want to do, we are using these drugs at the earlier stage because their efficacy is way more prominent earlier than later.
For example, blinatumomab has been approved by the FDA for [B-cell precursor ALL who are in remission] who have minimal residual disease (MRD); therefore, the use of the drug is more powerful if you use it earlier than later. At The University of Texas MD Anderson Cancer Center, we are using [blinatumomab] in the frontline setting, and in combination with other compounds in the relapse [setting]. Inotuzumab ozogamicin is also effective in the relapsed setting. At The University of Texas MD Anderson Cancer Center, we are using a strategy to combine low-dose chemotherapy with inotuzumab ozogamicin and blinatumomab for elderly people in the frontline setting and for the refractory setting. In the frontline setting for older people, we have a high response rate of 95%, MRD negativity approaching 95%, and the 3-year survival for these patients is 55%. This contrasts with historical data of only 15%, so it is a major advance that we are seeing.
In the relapsed setting, this combination has shown great results. For example, when you combine low-dose chemotherapy with inotuzumab ozogamicin and blinatumomab, we have a response rate of 85%. However, most importantly, the survival at 2 years and 3 years in the salvage setting is approaching 50%, which is a breakthrough. This combination has a median overall survival of 14 months, but is 25 months in the salvage setting, which is double and triple of what you could achieve with a single-agent drug.