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Chiaretti, S.1; Cesini, L.1; Di Raimondo, F.2; Angelucci, E.3; Luppi, M.4; Bonifacio, M.5; Cascavilla, N.6; Fozza, C.7; La Sala, E.8; Soddu, S.8; Fazi, P.8; Vitale, A.1; Foà, R.1; Ferrara, F.9

doi: 10.1097/01.HS9.0000558912.98111.4c
Poster Session I: Acute lymphoblastic leukemia - Clinical

1Department of Translational and Precision Medicine, Sapienza University of Rome, Rome

2Division of Haematology, Azienda Policlinico-OVE, Catania

3 Hematology and Bone Marrow Transplantation Unit, IRCCS Ospedale Policlinico San Martino, Genova

4Hematology Unit, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena

5Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona

6 Institute of Stem Cells Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), Fondazione IRCCS “Casa Sollievo della Sofferenza-IRCCS”, San Giovanni Rotondo

7 Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari

8Fondazione GIMEMA - Franco Mandelli Onlus, Rome

9Division of Hematology, Cardarelli Hospital, Naples, Italy

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The prognosis of acute lymphoblastic leukemia (ALL) in the elderly is poor and many patients (pts) are not included in clinical trials because of concomitant comorbidities/poor performance status (PS). In order to overcome these aspects, the GIMEMA designed a trial (LAL1104) for Ph-negative ALL (Ph- ALL) pts >60 years (ys).

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Aim of the study was to assess the overall survival (OS) of elderly Ph- ALL pts treated front-line according to a geriatric assessment.

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In the LAL1104 front-line phase II multicenter trial elderly Ph- ALL pts were stratified into 3 categories (fit, frail, intermediate), on the basis of a geriatric multidimensional evaluation: they were considered fit if they had normal activities of daily living (ADL), no grade (G) 2 comorbidities and no geriatric syndromes; intermediate if they had a normal ADL, G 2 comorbidities ≤2 and absence of geriatric syndromes; frail if they were >85 ys, had an abnormal ADL, G 2 comorbidities ≥3 or G 3 comorbidities ≥1, ≥1 geriatric syndromes. Treatment was more intensive for fit and intermediate pts: including daunorubicine 25 mg/m2 on days 1-3, 22-24 and vincristine 1.4 mg/m2 days 1, 8, 15, 22 in induction, and methotrexate (MTX) 1 g/m2 and cytarabine 1.5 g/m2 as consolidation, autologous transplantation (auto-SCT) in fit pts followed by maintenance with MTX, 6-mercaptopurine (6-MP) and vincristine; frail pts received vinblastine 5 mg/m2 on days 1, 8, 15, 22 as induction, and MTX and 6-MP as maintenance. All pts underwent central nervous system prophylaxis.

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From October 2007 to December 2016, 102 previously untreated elderly Ph- ALL pts were enrolled. Median age was 69.6 ys (range: 60.5-84.6), 85% were B-lineage ALL; t(4;11) was detected in 7% of pts. According to the geriatric evaluation, 49 pts (51%) were considered fit, 28 (29%) intermediate and 19 (20%) frail. Twenty pts (21%) had a PS ≥2. A response - complete + partial response, CR and PR - was achieved in 63 pts (63.5%); 17 pts (18%) died in induction. With a median follow-up of 52.8 months (range: 0.23-88.8) the 2- and 4-ys OS and disease-free survival (DFS) are 40.5% and 38.5%, and 22.1% and 19.5%, respectively. There were no differences in 2- and 4-ys OS and DFS (fit vs intermediate vs frail: 40% vs 43% vs 41% and 41% vs 32% vs 44%; 26% vs 19% vs 10% and 24% vs 19% vs 0%) according to the geriatric assessment; contrariwise, younger pts (60-70 ys) showed significantly better 2- and 4-ys OS than older pts (48% vs 30% and 32% vs 9%, respectively, p = 0.007, Figure). Fifteen pts (14%) underwent an auto-SCT, which was beneficial in terms of OS by a time dependent covariate analysis (p = 0.02). The most common G >2 adverse events were infections (41%), in particular sepsis (20%) and pneumonia (15%). Ten pts (10%) developed paralytic ileus during treatment, with intestinal perforation in 1; hepatic and cardiac toxicities were observed in 6 pts (6%). Peripheral neuropathy was reported in 6 pts (6%).



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Despite being less intensive than other trials designed for elderly ALL the GIMEMA 1104 trial designed for Ph- ALL pts compared favorably with literature data. As expected, age represented the most important prognostic factor in terms of OS. Importantly, the geriatric assessment proved effective in reducing early fatal side effects in unfit pts and abolished the differences in terms of OS, with a survival rate of 26% at 4-ys for the fit pts. Enrollment in clinical trials designed specifically for elderly Ph- ALL, including new drugs and a geriatric assessment, will likely improve further the survival rates of these difficult to treat pts.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.