Madhuri Vusirikala, MD, professor of internal medicine in the Division of Hematology/Oncology at the Harold C. Simmons Comprehensive Cancer Center of UT Southwestern Medical Center, discusses the benefit of hyperfractionated cyclophosphamide, vincristine, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) and the multitargeted TKI ponatinib (Iclusig) in patients with Philadelphia chromosome—positive ALL.  

At the 2019 ASH Annual Meeting, investigators from the University of Texas MD Anderson Cancer Center presented updated data on a trial examining the combination of hyper-CVAD and ponatinib in patients with Philadelphia chromosome—positive ALL, says Vusirikala.

These data continued to demonstrate that treatment with the combination have leads to much better response rates. Additionally, investigators were able to avoid transplant in this subgroup of high-risk patients. Prior to the introduction of TKIs, patients with Philadelphia chromosome—positive ALL were always recommended to undergo an allogeneic transplant because that was the only potentially curative approach, explains Vusirikala. Now, with the addition of TKIs, improved responses and cures without transplant have been reported in this patient population.

In fact, it appears that patients who are treated with ponatinib and hyper-CVAD, who go on to receive transplant, have a worse prognosis than those who continue on ponatinib without transplant, concludes Vusirikala.

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Madhuri Vusirikala, MD, discusses the benefit of hyper-CVAD and ponatinib in patients with Philadelphia chromosome–positive ALL.

Dr. Vusirikala on Hyper-CVAD Plus Ponatinib in Philadelphia Chromosome-Positive ALL

Madhuri Vusirikala, MD, professor of internal medicine in the Division of Hematology/Oncology at the Harold C. Simmons Comprehensive Cancer Center of UT Southwestern Medical Center, discusses the role of transplant in acute lymphoblastic leukemia (ALL).

ALL presents differently in adults compared with pediatric patients, says Vusirikala. In clinical trials, adolescents and young adults are typically those under the age of 39. While pediatric regimens are well established in B-ALL, the role of transplant is less clear. 

In Philadelphia chromosome (Ph)—like ALL, targetable markers such as BCR-ABL and JAK-STAT are beginning to emerge. As such, many studies in this space are evaluating the use of ruxolitinib (Jakafi) and dasatinib (Sprycel) as up-front treatment, says Vusirikala. However, more research is needed to determine whether transplant plays a role in this patient subset. In Ph-positive ALL, transplant is commonly used, especially in those with minimal residual disease (MRD) negativity.

A study from The University of Texas MD Anderson Cancer Center evaluated the MRD status of patients with Ph—positive ALL after 3 months post treatment with hyper-CVAD and a TKI. If patients test positive for MRD, they may benefit from transplant, says Vusirikala.

At UT Southwestern Medical Center, patients with Ph—positive ALL are treated with hyper-CVAD and a TKI. At the end of induction, patients undergo a bone marrow biopsy to see whether they are in a complete molecular response. If so, patients are given maintenance therapy with 2 years of vincristine, steroids, and indefinite TKIs. If patients have MRD-positive disease, they are taken to transplant, concludes Vusirikala.

Madhuri Vusirikala, MD, discusses the role of transplant in acute lymphoblastic leukemia.

Dr. Vusirikala on the Role of Transplant in ALL

Madhuri Vusirikala, MD, professor of internal medicine in the Division of Hematology/Oncology at the Harold C. Simmons Comprehensive Cancer Center of UT Southwestern Medical Center, discusses ongoing research with blinatumomab (Blincyto) in acute lymphoblastic leukemia (ALL).

Blinatumomab is being used in the up front setting, as it is a highly effective agent in ALL, says Vusirikala. At UT Southwestern Medical Center, the ECOG-ACRIN 1910 trial is evaluating blinatumomab in the frontline setting. Patients who have minimal residual disease (MRD) after 2 cycles of induction chemotherapy are assigned to receive blinatumomab. Patients with MRD-negative ALL at the end of induction intensification are randomized to receive blinatumomab versus no blinatumomab. The trial will determine whether blinatumomab has a role in patients who have MRD-negative disease at the end of induction therapy, says Vusirikala. Blinatumomab is also being examined in the pediatric setting.

Notably, there is concern that blinatumomab could lead to increased risk of graft-versus-host-disease (GVHD) if used after transplant, as it is an immune-based therapy. However, there are no data to suggest that the agent causes an increased risk of GVHD in optimally selected patients, concludes Vusirikala.

Dr. Vusirikala on Ongoing Research With Blinatumomab in ALL

Madhuri Vusirikala, MD, professor of internal medicine in the Division of Hematology/Oncology at the Harold C. Simmons Comprehensive Cancer Center of UT Southwestern Medical Center, discusses the role of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL).

Data have shown that allogeneic stem cell transplantation is the only potential cure for patients with ALL, regardless of MRD status, says Vusirikala. It is known that patients with MRD-negative disease have a better outcome with a transplant.

However, a subset of MRD-positive patients can experience improved outcomes or even cure from transplant, adds Vusirikala. Although patients with MRD positivity can still be taken to transplant, Vusirikala says it’s important to be cognizant that these patients have a high risk of relapse.

Performing a lymphocyte infusion or giving agents like blinatumomab (Blincyto) or inotuzumab ozogamicin (Besponsa) post-transplant may significantly reduce the risk of relapse for these patients, concludes Vusirikala.

Madhuri Vusirikala, MD, discusses the role of minimal residual disease in acute lymphoblastic leukemia.

Madhuri Vusirikala, MD

Articles

Dr. Vusirikala on Hyper-CVAD Plus Ponatinib in Philadelphia Chromosome-Positive ALL

Dr. Vusirikala on the Role of Transplant in ALL

Dr. Vusirikala on Ongoing Research With Blinatumomab in ALL

Dr. Vusirikala on the Role of MRD in ALL