SOHO 2024: Advancements in ALL, CML, and CLL Treatment Strategies
Key Insights
Targeted therapies in childhood ALL (search) show promise, with ponatinib plus blinatumomab achieving high remission and survival rates, reducing chemotherapy and transplant needs.
Asciminib demonstrates higher major molecular response rates at 12 months compared to other tyrosine kinase inhibitors in CML (search), but faces challenges in long-term survival and cost-effectiveness.
Lisocabtagene maraleucel in relapsed/refractory CLL (search) shows that less pretreated patients with lower tumor burden may benefit more from CAR T-cell therapy.
The Society of Hematologic Oncology (SOHO) 2024 Annual Meeting featured groundbreaking studies in hematologic oncology, focusing on acute lymphoblastic leukemia (search) (ALL (search)), chronic myeloid leukemia (search) (CML (search)), and chronic lymphocytic leukemia (search) (CLL (search)). Experts Hagop M. Kantarjian, MD, FASCO, and Nitin Jain, MD, from The University of Texas MD Anderson Cancer Center, shared insights into pivotal studies presented at the conference.
Precision Treatment for Childhood ALL
Ching-Hon Pui, MD, of St. Jude Children’s Research Hospital, presented on precision medicine in childhood ALL (search), highlighting a shift toward targeted therapies. The current standard treatment involves an intensive chemotherapy regimen over 3 years, achieving cure rates of 80% to 90% in children and 40% to 50% in adults in controlled trials. However, real-world results show lower cure rates due to treatment intensity and duration, especially in emerging nations.
For Philadelphia chromosome–positive ALL (search), combining ponatinib, a third-generation BCR::ABL1 (search) tyrosine kinase inhibitor, with blinatumomab, a CD19 (search) bispecific T-cell engager, has shown remarkable results. "Almost all the patients achieved complete remission," said Dr. Kantarjian. "These remissions were deep, and the estimated 4-year survival rate was close to 90%, which is something we’ve never seen before." This approach also reduced the need for chemotherapy and transplantation.
In Philadelphia chromosome–negative precursor B-cell ALL (search), combining reduced chemotherapy with blinatumomab and inotuzumab ozogamicin resulted in an estimated 4-year survival rate exceeding 80% in younger patients. These new regimens are better tolerated and can be delivered in less than half the time compared to traditional intensive chemotherapy.
Asciminib vs Tyrosine Kinase Inhibitor Therapy in CML
Jorge E. Cortés, MD, of Georgia Cancer Center, presented a randomized study comparing asciminib, a third-generation BCR::ABL1 (search) tyrosine kinase inhibitor, with tyrosine kinase inhibitors of choice in newly diagnosed Philadelphia chromosome–positive CML (search). The study met its primary endpoint, showing a higher rate of major molecular response at 12 months with asciminib. However, it did not demonstrate a statistically significantly higher major molecular response rate compared specifically with second-generation tyrosine kinase inhibitors.
Dr. Kantarjian outlined the evolution of CML (search) treatments, noting that while second-generation tyrosine kinase inhibitors show higher rates of early surrogate endpoints, they have not demonstrated improved survival. He also highlighted the shift toward using optimal biologic doses rather than maximum tolerated doses to reduce long-term toxicities. For example, halving the dose of dasatinib to 50 mg/d retains the same efficacy while significantly reducing toxicities.
Dr. Kantarjian outlined key criteria for adopting asciminib in the front-line setting: improved long-term survival, higher rate of treatment-free remission, similar or reduced side effects, and good treatment value. Asciminib's high cost, currently priced at about $320,000 a year, presents a significant barrier to its adoption.
Lisocabtagene Maraleucel in Relapsed/Refractory CLL
Dr. Jain discussed a post hoc exploratory analysis of the phase I/II TRANSCEND CLL (search) 004 study, presented by William Wierda, MD, PhD, evaluating lisocabtagene maraleucel, the only CAR T-cell therapy approved for CLL. The analysis aimed to identify characteristics associated with response to lisocabtagene maraleucel in relapsed or refractory CLL/small lymphocytic lymphoma.
Among 87 patients, the rate of complete remission was 18%, the overall response rate was 47%, and the median progression-free survival was 18 months. The analysis revealed that baseline genomic characteristics did not significantly influence response rates. However, patients who achieved a response had a median of four prior therapies, compared with six for nonresponders, suggesting that less heavily pretreated patients might benefit more. Patients with lymph nodes smaller than 5 cm were also more likely to respond.
Factors associated with an increased risk of neurotoxicity included high inflammatory markers, bulky disease, and lower creatinine clearance. Despite these insights, the findings are unlikely to significantly change clinical practice, and there remains an ongoing unmet need in CLL (search) treatment. Future research should focus on developing better CAR T-cell therapy and combining CAR T-cell therapies with other strategies to improve outcomes.