Treatment of older patients with acute lymphoblastic leukemia

Abstract

The treatment of older patients with acute lymphoblastic leukemia (ALL) is an unmet medical need. With increasing age, ALL patients have a significantly lower clinical remission rate, higher early mortality, higher relapse rate, and poorer survival compared with younger patients. This is only partly explained by a higher incidence of poor prognostic factors in the older age group. Most importantly, intensive chemotherapy with or without stem cell transplantation (SCT) is less well tolerated in older patients. Some progress has been made with delivering age-adapted, moderately intensive chemotherapy protocols for Ph/BCR–ABL-negative ALL and combinations of tyrosine kinase inhibitors with chemotherapy in Ph/BCR–ABL-positive ALL. For the future, optimizing supportive care, introducing targeted therapies, novel immunotherapies, moderately intensified consolidation strategies, and reduced intensity SCT are promising approaches. Prospective clinical trials for older patients are urgently needed to test these approaches.

Guidelines Insights: Acute Lymphoblastic Leukemia, Version 1.2019

“…In particular, older adults are more likely to have ALL with high-risk genetics, including Ph-positive disease, MLL rearrangements, or TP53 mutation. 11,12 Notably, Ph-like B-ALL, a high-risk subgroup, is also common in older patients, estimated at 24% in one large series. 13 Often superimposed on this high-risk genetic background is an increased incidence and severity of comorbid conditions, poor functional status, and lower systemic and hematopoietic reserve, culminating in higher rates of adverse drug interactions and treatment-related death.…”

“…13 Often superimposed on this high-risk genetic background is an increased incidence and severity of comorbid conditions, poor functional status, and lower systemic and hematopoietic reserve, culminating in higher rates of adverse drug interactions and treatment-related death. 11 However, these findings should not be interpreted as an indication to withhold intensive therapy, but rather stress the importance of tailoring therapy, as highlighted by the German Multicenter Study Group for Adult ALL (GMALL). 3 Unfortunately, older patients with newly diagnosed ALL often do not receive chemotherapy or bone marrow transplant, highlighting the need for guidance in this population.…”

Current challenges and opportunities in treating adult patients with Philadelphia‐negative acute lymphoblastic leukaemia

“…The 5‐year OS was halved in this group (21% vs. 41%) and ED was more than 4‐times higher (18% vs. 4%) (Sive et al , ). This excess toxicity may reflect the effect of comorbidities and co‐medications in older adults as well as pharmacokinetic and pharmacodynamic alterations associated with aging (Gokbuget, ). Asparginase during induction seems to significantly increase toxicity and ED (Sancho et al , ; Fathi et al , ) that can be reduced if asparginase is delayed until the post‐remission phases (Gokbuget et al , ).…”

“…Other studies incorporated liposomal anthracyclines to therapy with mixed results (Offidani et al , ; Hunault‐Berger et al , ). Aggressive supportive care with prophylactic antibiotics and growth factors are complementary strategies to reduce ED in this population (Larson et al , ; Gokbuget, ).…”

“…This BFM‐based reduced protocol includes asparginase‐free induction phases followed by 6 alternating cycles with intermediate‐dose MTX combined with asparginase and high‐dose cytarabine. Using this approach in older patients, the GMALL and Programme for the Study and Treatment of Haematological Malignancies (PETHEMA) groups reported CR rates of 85% and 74%, respectively (Gokbuget, ). The OS was 61% for the German study at 1 year and 30% for the Spanish study at 2 years (Gokbuget, ).…”