Chemotherapy May Eliminate Need for Allogeneic Stem Cell Transplant for Newly Diagnosed Patients with ALL, Relapsed/Refractory ALL

Routine allogeneic stem cell transplant (SCT) is not necessary for most patients with newly diagnosed acute lymphocytic leukemia (ALL) and for many patients with relapsed/refractory ALL due to the ideal use of other currently available agents, according to a session presented at the 10th Annual Meeting of the Society of Hematologic Oncology, held in Houston, Texas.

Nicholas Short, MD, assistant professor in the Department of Leukemia at the MD Anderson Cancer Center, discussed previous studies supporting tools that did not provide a survival benefit. When standard therapies are given, poor-risk cytogenetics and poor minimal residual disease (MRD) clearance occur in relation to the identification of high-risk subtypes that undergo SCT in CR1.

Short discussed novel agents as well as potent tyrosine kinase inhibitors (TKIs), chemotherapy in Ph+ ALL, and the addition of an anti-CD20 antibody to chemotherapy in Burkitt and pre B-ALL, which are blinatumomab, inotuzumab ozogamcin, and chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory disease.

“We want to prioritize the best available agents like these in the frontline setting and in combination,” Short said.

Adding first-, second-, and third-generation TKIs have helped to increase molecular response rates and survival with successive generation of TKIs, but Short still questioned the role of intensive chemotherapy versus low-intensity (or even chemotherapy-free) regimens. Additionally, the role of SCT in first remission with optimal therapy for Ph+ ALL is in question.

The GIMEMA LAL2116 D-ALBA trial analyzed 63 patients with newly diagnosed Ph+ ALL who were treated with dasatinib plus blinatumomab, with a primary endpoint of complete metabolic response after 2 cycles. Further, 95% of patients reached the overall survival goal, with 6 relapses being evaluated (3 hematologic, 2 central nervous system, and 1 nodal). As for survival outcomes for the frontline cohort, only 1 patient transplanted with event-free survival.

The trial investigators found that next-generation sequencing (NGS) MRD was prognostic after CAR T-cell therapy for ALL, with NGS MRD status at 3-months superior to B-cell aplasia/recovery at predicting relapse/survival.

As for the real-world outcomes of tisagenlecleucel, there was lower disease burden associated with superior survival and better toxicity profile, according to Short. Out of 185 children or younger adults treated with commercial tisagenlecleucel for relapsed/refractory B-cell ALL, 98% of patients had a response of low-disease burden.

Short mentioned that although SCT may not improve outcomes in relapsed/refractory B-cell when optimal salvage therapy is given, the role of CAR T-cell consolidation is unknown. Further, he said health care providers need to learn to use the tools they already have available and strengthen them.

“We should rely heavily on MRD tools to help patients, and we should continue to limit transplant for patients and cure them with the drugs we currently have available,” Short said.

REFERENCE

Short, Nicholas. Novel Chemotherapy Can Eliminate the Need for Transplantation ALL. September 28th, 2022. Accessed October 4, 2022. 10th Annual Meeting of the Society of Hematologic Oncology. Houston, Texas.