Imatinib in Very Elderly (> 75 years) CML Patients: Are Low-Doses (<400 mg daily) Enough?
Authors: Latagliata Roberto , Breccia Massimo , Ferrero Dario , Cavazzini Francesco , Trawinska Malgorzata Monika , Castagnetti Fausto , Annunziata Mario , Stagno Fabio , Tiribelli Mario , Imbergamo Silvia , Fava Carmen , Crisà Elena , Pietrantuono Giuseppe , Gozzini Antonella , Falzetti Franca , Montefusco Enrico , Iurlo Alessandra , Musolino Caterina , Cedrone Michele , Rossi Antonella Russo , Pregno Patrizia , Visani Giuseppe , Capodanno Isabella , Endri Mauro , Spadea Antonio , Giglio Gianfranco , Celesti Francesca , Sica Simona , Storti Sergio , D'Addosio Ada M , Cambrin Giovanna Rege , Luciano Luigiana , Abruzzese Elisabetta , Rosti Gianantonio , Alimena Giuliana 
Published: October 2019

Abstract
Abstract 2770
In the “real world” of clinical practice, often physicians choose to treat very elderly CML patients with imatinib (IM) at lower than standard (400 mg/day) dose, but there are no published data on the results. To highlight this issue, we retrospectively revised 200 > 75 years old CML patients in chronic phase treated with IM 29 haematological Italian Institutions. We compared 58 patients (29%) who received low-dose IM (≤ 300 mg/day) according to physician decision (LD group) with the remaining 142 patients (71%) who received standard dose IM (SD group). In the SD group, there were 73 males and 69 females with a median age at IM start of 77.9 years (IR 76.0–80.3), Sokal Risk at diagnosis was low in 3 patients, intermediate in 86, high in 39 and not evaluable in 12. Two or more concomitant diseases requiring specific treatments were present in 93/142 patients (65.4%), with 85 patients (59.8%) taking 3 or more concomitant drugs. Twenty-seven patients (19.0%) were in late chronic phase (≥ 12 months from diagnosis before starting IM); on the whole, median time from diagnosis to IM was 1.1 months (IR 0.5–3.0). In the LD group, there were 31 males and 27 females with a median age of 80.2 years (IR 77.9–84.5) at IM start, Sokal Risk at diagnosis was intermediate in 34 patients, high in 17 and not evaluable in 7. Two or more concomitant diseases requiring specific treatments were present in 43/58 patients (74.1%), with 43 patients (74.1%) taking 3 or more concomitant drugs. Fifteen patients (25.8%) were in late chronic phase; on the whole, median time from diagnosis to IM was 1.8 months (IR 0.7–10.4). Starting dose of IM was 300 mg/day in 44 patients (75.8%) and < 300 mg/day in 14 patients (24.2%). According to CTC-AE, grade 3–4 hematological and extra-hematological toxicities were observed in 29 (20.4%) and 30 (21.1%) patients in the SD group compared with 10 (17.2%) and 14 (24.1%) patients in the LD group, respectively. Overall, 63 patients in the SD group (44.3%) required a dose reduction compared to 13 (22.4%) in the LD group (p=0.004): eleven (7.7%) patients in the SD group discontinued IM for toxicity compared to 13 (22.4%) in the LD group (p=0.004). Response to IM in the 2 groups is detailed in the table.SD groupLD grouppN° patients evaluable for response13656Early discontinuation8 (5.8%)8 (14.3%)0.054Resistant disease3 (2.2%)1 (1.8%)0.859Complete haematological response only24 (17.6%)12 (21.4%)0.527Partial cytogenetic response9 (6.6%)6 (10.7%)0.329Complete cytogenetic response92 (67.6%)29 (51.8%)0.052Major molecular response69 (50.7%)17 (30.3%)0.012
After a median follow-up of 33.7 months (IR 18.1–64.7), in the SD group 35 patients died (5 from disease progression and 30 from unrelated causes), 5 patients were lost to follow-up and 102 are still alive: in the LD group, 15 patients died (3 from disease progression and 12 from unrelated causes), 3 patients were lost to follow-up and 40 are still alive. In the SD group, 2-year and 5-year overall survival were 93.2% (CI95% 88.6–97.2) and 65.7% (CI95% 55.0–76.3), respectively; in the LD group, 2-year and 5-year overall survival were 89.7% (CI95% 80.4–98.9) and 67.0% (CI95% 49.6–84.4), respectively. In conclusion, in very elderly CML patients even reduced IM dose appears to be safe and effective enough to achieve sustained cytogenetic and molecular responses with prolonged overall survival. Therefore, also very elderly patients with co-morbidities should have this chance of cure without no upper age limit.

Disclosures:
Russo Rossi: Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Rosti:Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Research Funding; Novartis: Honoraria; Bristol Myers Squibb: Honoraria.