Steven Coutre, MD, professor of medicine at Stanford University Medical Center, discusses combination strategies for the treatment of patients with acute lymphoblastic leukemia (ALL).

For patients with ALL, the backbone is multi-agent chemotherapy, says Coutre. The concept of using non-cross resistant agents was one of the advances shown in ALL. Newer drugs are not being used except blinatumumab (Blincyto) post induction, which is being investigated in a trial for patients age 40 and older. There is another trial for younger patients using a chemotherapy backbone and randomizing patients post remission to inotuzumab ozogamicin (Besponsa). However, physicians are unsure if using these newer agents earlier in treatment will change the natural history of disease and cause fewer patients to relapse, Coutre adds.

According to Coutre, there are still remaining questions involving minimal residual disease-assessment and if that can be used to identify patients very early who are at higher risk of relapse, as well as better identify their therapy.

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Dr. Coutre Discusses Combination Strategies in ALL

Steven Coutre, MD, professor of medicine at Stanford University Medical Center, discusses challenges with chimeric antigen receptor (CAR) T-cell therapy in acute lymphoblastic leukemia (ALL).

Tisagenlecleucel (Kymriah), the first FDA-approved CAR T-cell therapy, is approved for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse. However, it is not approved in adults, and Coutre says that it is not yet known whether CAR T-cell therapy will be used with a curative intent or as a bridge to transplant.

In pediatric patients, investigators are looking to move tisagenlecleucel to earlier lines of therapy. But, if issues with toxicities can be better defined, Coutre says that CAR T-cell therapy may be appropriate for some patients above the current indicated age range.

Steven Coutre, MD, professor of medicine at Stanford University Medical Center, discusses challenges with chimeric antigen receptor (CAR) T-cell therapy in acute lymphoblastic leukemia.
 

Dr. Coutre Discusses Challenges With CAR T-Cell Therapy in ALL

Steven Coutre, MD, professor of medicine at Stanford University Medical Center, discusses the role of blinatumomab (Blincyto) for patients with minimal residual disease (MRD)-positive acute lymphoblastic leukemia (ALL).

Blinatumomab is a newer antibody therapy that has shown benefit in treating patients with MRD-positive disease by eliciting MRD-negative remissions, says Coutre. This drug was approved in patients who have relapsed, and is currently being used in randomized trials as upfront therapy. These trials are looking at blinatumomab post-remission, evaluating whether it decreases the risk of relapse.

The FDA’s Oncologic Drugs Advisory Committee (ODAC) is slated to review a supplemental biologics license application for the use of blinatumomab for the treatment of patients with MRD-positive ALL. Investigators found that complete MRD response was associated with significantly improved survival. Compared with nonresponders, the patients who had complete MRD response had superior relapse-free survival (23.6 vs 5.7 months; 

= .002) and overall survival (OS; 38.9 vs 12.5 months; 

Dr. Coutre Discusses Blinatumomab in MRD-Positive ALL

Steven Coutre, MD, professor of medicine (hematology) at Stanford University Medical Center, discusses considerations when selecting between oral therapies like ibrutinib and chemoimmunotherapy for first-line treatment of chronic lymphocytic leukemia (CLL).

When determining frontline treatment, it is important to consider each patient’s individual needs, and not just make a medical-based decision, says Coutre.

A frail patient or a patient with multiple comorbidities may not be able to tolerate a chemoimmunotherapy regimen, and should therefore be given an oral regimen.

Financial constraints may also need to be a considered for some patients. A defined course of therapy like chemoimmunotherapy may be fully reimbursed by insurance, while a long-term oral therapy may not be, says Coutre.

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​Steven Coutre, MD, professor of medicine (hematology) at Stanford University Medical Center, discusses considerations when selecting between oral therapies like ibrutinib and chemoimmunotherapy for first-line treatment of chronic lymphocytic leukemia (CLL).

Dr. Steven Coutre on Frontline Treatment Decisions in CLL

Steven Coutre, MD, professor of medicine (Hematology), Stanford University Medical Center, discusses the eventual role chemotherapy will have in the treatment of chronic lymphocytic leukemia (CLL).

With agents ibrutinib and idelalisib proving to be efficacious in treatment of CLL, Coutre explains more patients are steering away from chemotherapy as a treatment option. There is also more tolerability with these agents, he says.

Researchers are also conducting randomized trials in the frontline setting comparing ibrutinib and idelalisib to chemotherapy. If these results are positive in respect to the novel agents, the trend towards them will further accelerate, Coutre predicts.

Coutre says a remarkable accomplishment would be for the average patient, who is at least 70 years of age and in need of initial therapy, to be able to receive an oral, well-tolerated agent such as ibrutinib or idelalisib. Though this agent may not eliminate their disease, it could have the potential to manage it for the rest of their life.

Steven Coutre, MD, professor of medicine, Stanford University Medical Center, discusses the eventual role chemotherapy will have in the treatment of chronic lymphocytic leukemia.


Steven Coutre, MD

Articles

Dr. Coutre Discusses Combination Strategies in ALL

Dr. Coutre Discusses Challenges With CAR T-Cell Therapy in ALL

Dr. Coutre Discusses Blinatumomab in MRD-Positive ALL

Dr. Steven Coutre on Frontline Treatment Decisions in CLL

Dr. Steven Coutre on the Eventual Role of Chemotherapy in CLL