Different Prognosis According to Subtype-Oriented Protocols in Elderly Patients with Acute Lymphoblastic Leukemia (ALL). Comparison of Three Prospective Parallel Trials from the Pethema Group
Authors: Ribera Josep-Maria , Garcia Olga , Fernandez Pascual , Montesinos Pau , Brunet Salut , Martinez Maria del Pilar , Lavilla Esperanza , Bernal Teresa , González Jose , Tormo Mar , Barba Pere , Monteserín Carmen , Sarrá Josep , Fernandez Marta , Colorado Mercedes , Novo Andrés , Garcia Antonio , Calbacho Maria , Abella Eugenia , Moreno Maria-Jose , Hernández-Rivas Jesús-Maria , Lopez Maria-Elsa , Alonso Natalia , Serrano Alfons , Feliu Evarist 
Published: October 2019

Abstract

Background and objective
ALL in elderly patients is associated with poor prognosis and many patients are not included in therapeutic trials. Consequently, the results of subtype-oriented protocols in elderly ALL are poorly known. We present the results of three prospective parallel subtype-oriented protocols from the Spanish PETHEMA group in ALL patients older than 55 years.

Patients and Methods
In 2008 three prospective phase II trials for ALL patients older than 55 yr with the Charlson Comorbidity Index ≤3 were activated: ALLOld07 (Ph-negative patients, NCT01366898, n=54), ALLOPh07 (Ph-positive patients, NCT01376427, n=48) and BURKIMAB08 (mature B-ALL, NCT00388193, n=18). The ALL0ld07 protocol included moderate-dose induction chemotherapy without genotoxic drugs, followed by consolidation and maintenance therapy for 2 years (Gökbuget et al, ASH 2008), the ALL OPh07 included imatinib and dexamethasone for induction followed by maintenance therapy with mercaptopurine and methotrexate and imatinib for 2 years, followed by imatinib for one additional year (Ribera et al, Br J Haematol 2012; 159: 485-488), and the BURKIMAB08 protocol included specific therapy for Burkitt’s lymphoma/leukemia together with rituximab (Ribera et al, Cancer 2013; 119:1660-8). The main outcomes (early death [ED], complete remission [CR], remission duration [RD] and overall survival [OS]) and toxicity (CTCAE v4.0) were compared.

Results
40, 45 and 16 patients from ALLOld07, ALLOPh07 and BURKIMAB08, respectively, were evaluable for this study. Patients with mature B-ALL were more frequently male, with poorer general status, higher frequency of bulky disease and higher LDH serum levels, whereas no significant differences were observed on comparison of ALLOld07 and ALLOPh07 patients. The comparison of the main outcomes of the three trials is shown in Table 1. By multivariate analyses for RD the protocol and WBC count were identified as prognostic factors (BURKIMAB08 was considered as reference category), with HR [95%CI] of 6.8 [0.9-52.1], p=0.064, when compared with ALL Old07 and 3.1 [0.4-24.8], p=0.278 when compared with ALL OPh07, global p value=0.042, and HR [95%CI]: 1.004 [1-1.009], p=0.058 for the WBC count, respectively. The ECOG score was the only variable influencing OS (HR [95%CI]: 0.4 [0.2;0.8], p=0.003).
Hematological toxicity in induction and consolidation as well as infections were significantly less frequent in ALLOPh07 than in other two trials, whereas renal toxicity was more frequent in BURKIMAB08.

Conclusion
Risk-adapted therapy in elderly patients with ALL was feasible and produced significantly different results in terms of CR duration, being the best for mature B-ALL and the poorest for Ph-negative ALL.
Supported by the grants PI10/01417 from FIS and RD12-0036-0029 from Instituto Carlos III

Disclosures:
No relevant conflicts of interest to declare.