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1486 Hemoglobin Changes during Long-Lasting Frontline Treatment with Tyrosine-Kinase Inhibitors in Patients with Chronic Myeloid Leukemia

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Clinical Research, Clinically Relevant, Real World Evidence, Myeloid Malignancies, Study Population, Clinical Practice (e.g. Guidelines, Health Outcomes and Services, and Survivorship, Value; etc.)
Saturday, December 11, 2021, 5:30 PM-7:30 PM

Roberto Latagliata1*, Ida Carmosino, MD2*, Ambra Di Veroli, MD1*, Emilia Scalzulli, MD3*, Gioia Colafigli, MD4*, Maria Cristina Scamuffa, MD5*, Alessio Di Prima, MD5*, Cinzia De Gregoris, MD1*, Sara Pepe, MD4*, Marco Mancini, MD6*, Giulio Trapè, MD1*, Maurizio Martelli, MD2*, Robin Foa, MD2 and Massimo Breccia, MD2*

1Hematology, Belcolle Hospital, Viterbo, Italy
2Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
3Hematology, Department of Translational and Precision Medicine, Policlinico Umberto I, Sapienza University, Rome, Italy
4Department of Traslational and Precision Medicine - Hematology, University Sapienza, Rome, Italy
5Hematology, Department of Translational and Precision Medicine, Sapienza University, Policlinico Umberto I, Roma, Italy
6Hematology, Department of Translational and Precision Medicine, "Sapienza" University, Rome, Italy

Introduction Chronic Myeloid Leukemia (CML) has become highly curable after introduction of Tyrosine-Kinase Inhibitors (TKIs). However, several side-effects have been reported with the prolonged use of TKIs: in particular, severe cardiovascular and pulmonary toxicities were observed with 2nd generation TKIs (2G-TKIs), nilotinib and dasatinib. Imatinib is generally considered safer, even if some concerns were recently raised on its renal toxicity and occurrence of late anemia.

Aims To evaluate the impact of imatinib compared to 2G-TKIs on the hemoglobin (Hb) levels in the long-lasting frontline treatment of CML patients.

Methods From 1/2002 to 12/2015, 365 CML patients were diagnosed and treated frontline with TKIs in 2 different Centres in Italy: of them, 123 permanently discontinued the treatment before the 5th year from the start due to intolerance (31 cases, 25.2%), primary resistance (41, 33.3%), secondary resistance (16, 13.0%), blastic evolution (4, 3.2%), unrelated death (12, 9.8%) or were lost to follow-up (19, 15.5%). At 5 years, the remaining 242 patients were still receiving frontline TKI treatment and were considered for the present analysis. Hb levels were recorded at baseline and thereafter every 12 months up to the 5th year of treatment.

Results As to frontline treatment, 186 patients (76.8%) received imatinib and 56 (23.2%) 2G-TKIs (nilotinib in 44 cases and dasatinib in 12, respectively). The main clinical features at diagnosis of the entire cohort and according to frontline treatment are reported in the table: median Hb value at baseline was significantly lower in patients treated with 2G-TKIs. Median Hb values at different time-points according to frontline treatment are reported in the Figure. In patients treated with imatinib, median Hb levels at 12th (12.5 g/dl, IQR 11.6-13.5) and 60th month (12.4 g/dl, IQR 11.4-13.3) were stable compared to baseline (12.8 g/dl, IQR 11.3-13.8) (p=0.248 and p=0.075, respectively). On the contrary, median Hb levels at 12th (13.4 g/dl, IQR 12.2-14.3) and 60th month (13.6 g/dl, IQR 12.0-14.6) showed a significant increase compared to baseline (11.8 g/dl, IQR 10.6-13.7) in patients treated with 2G-TKIs (p<0.001 in both cases). As a consequence, during the treatment median Hb values became significantly higher at any different time-point in patients treated with 2G-TKIs compared to patients treated with imatinib (p=0.005 at the 12th month, p=0.010 at the 60th month). At baseline, the rate of patients with mild to moderate anemia (Hb < 11 g/dl) was significantly lower in those treated with imatinib [34/186 (18.2%) vs 20/56 (35.7%) treated with 2G-TKIs, p=0.006]: at the 12th month, no difference was observed [15/186 (8.0%) in patients treated with imatinib vs 3/56 (5.3%) in patients treated with 2G-TKIs, p=0.498], while at the 60th months the rate of patients with mild to moderate anemia became significantly higher in those treated with imatinib [29/186 (15.6%) vs 2/56 (3.6%) treated with 2G-TKI, p=0.018].

Conclusions Present data highlight that long-lasting treatment with imatinib can have a negative late effect on erythropoiesis, with incomplete recovery of hemoglobin levels and occurrence of late anemia in about 15% of patients at the 60th month of therapy.This possible adverse event, which is still unrecognized and seems very rare with 2G-TKIs, could affect quality of life and should be recognized in the long-term management of CML patients.

Disclosures: Latagliata: BMS Cellgene: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Martelli: Novartis: Other: advisory board; Gilead: Other: advisory board. Breccia: Pfizer: Honoraria; Novartis: Honoraria; Incyte: Honoraria; Bristol Myers Squibb/Celgene: Honoraria; Abbvie: Honoraria.

*signifies non-member of ASH