Comparison of intensive, pediatric-inspired therapy with non-intensive therapy in older adults aged 55–65 years with Philadelphia chromosome-negative acute lymphoblastic leukemia

Highlights

• In older adults intensive therapy yields better outcomes than semi-intensive therapy.

• In these patients the frequency of HSCT in first CR is low.

• As results of chemotherapy are poor, new therapy approaches are necessary.

Abstract

Background and objective

The standardization of treatment of older adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) is challenging, especially in the age range of 55–65 years. This study aimed to compare intensive, pediatric-inspired therapy with non-intensive therapy in this population of patients.

Patients and methods

The outcomes of 67 patients prospectively included in two consecutive pediatric-inspired intensive protocols (ALL-HR03 and ALL-HR11) from the Spanish PETHEMA Group were compared with those from 44 patients included in a contemporary semi-intensive protocol (ALL-OLD07).

Results

Baseline patient and ALL characteristics were similar in both groups, except for a younger median age in the intensive group (medians: 58 vs. 62 years). Patients treated intensively had a higher complete remission rate (85% vs. 64%, p = 0.005), a lower cumulative incidence of relapse (39% [95%CI, 25% to 52%] vs. 60% [95%CI, 38% to 77%], p = .003), a similar cumulative incidence of treatment-related mortality (28% [95% CI, 18%, 40%] vs. 21% [95% CI, 10%, 34%]) and superior event-free survival at 2 years (37% [95%CI, 25%–49%) vs. 21% [8%-34%], p = 0.002). On multivariable analysis the type of protocol was the only variable with independent significance for event-free survival (HR [95% CI]: 2 [1.3, 3], p = .002).

Conclusions

Compared with less intensive chemotherapy, pediatric-inspired intensive chemotherapy significantly improves the outcome of older adults with Ph-negative ALL in the age range of 55–65 years.

Introduction

The results of the treatment of Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in adults have improved in recent years [1]. The use of pediatric-like protocols in the younger adult (YA) population partially explains this improvement. Intensified pediatric-inspired regimens with continuous dose-intense exposure to chemotherapy and higher cumulative doses of non-myelotoxic drugs such as L-asparaginase and glucocorticoids are currently used by most groups to treat ALL in adult patients [[2], [3]]. However, the definition of the population likely to benefit from a pediatric-like approach remains controversial, especially for the upper age limit for using these pediatric-based protocols. In fact, this limit ranges from 30 years to 55 years among the different studies [[4], [5], [6], [7], [8], [9], [10], [11], [12]]. As treatment compliance and tolerability worsens in patients older than 55 years, treatment of these patients remains a challenge, especially for those aged between 55 and 65 years, in whom a balance between effectiveness and toxicity is difficult to assess. This explains the lack of standardization of the treatment of these older patients in current clinical practice, where the election between intensive, pediatric-inspired versus semi-intensive therapy is frequently individualized according to physicians and/or patients pReferences

Although in the protocols of the Spanish PETHEMA (Programa Español de Tratamientos en Hematología) Group intensive chemotherapy based on high-risk ALL protocols is recommended for fit adults aged 55–65 years, the final decision is taken by the participating physicians. As specific analyses of outcomes according to the intensity of the therapy in the age group of 55–65 years are scarce [13], the aim of this study was to analyze and compare the baseline characteristics, the results of treatment and the outcomes of older adults (55–65 years) with Ph-negative ALL included in two consecutive intensive pediatric-based protocols vs. those from one concurrent semi-intensive protocol from the PETHEMA Group.