Molecular response and quality of life in chronic myeloid leukemia patients treated with intermittent TKIs: First interim analysis of OPTkIMA study

• Published in: Cancer medicine (Malden, MA) Vol. 10; no. 5; pp. 1726 - 1737
• Main Authors: Malagola, Michele, Iurlo, Alessandra, Abruzzese, Elisabetta, Bonifacio, Massimiliano, Stagno, Fabio, Binotto, Gianni, D’Adda, Mariella, Lunghi, Monia, Crugnola, Monica, Ferrari, Maria Luisa, Lunghi, Francesca, Castagnetti, Fausto, Rosti, Gianantonio, Lemoli, Roberto M., Sancetta, Rosaria, Coppi, Maria Rosaria, Corsetti, Maria Teresa, Rege Cambrin, Giovanna, Romano, Atelda, Tiribelli, Mario, Russo Rossi, Antonella, Russo, Sabina, Aprile, Lara, Gandolfi, Lisa, Farina, Mirko, Bernardi, Simona, Polverelli, Nicola, Roccaro, Aldo M., De Vivo, Antonio, Baccarani, Michele, Russo, Domenico
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2021; John Wiley and Sons Inc; Wiley
• Subjects: Age; Aged; Aged, 80 and over; chronic myeloid leukaemia; Chronic myeloid leukemia; Clinical Cancer Research; Clinical trials; Dasatinib - administration & dosage; Dasatinib - adverse effects; Disease Progression; Drug Administration Schedule; Enrollments; Female; Humans; Hypotheses; Imatinib; Imatinib Mesylate - administration & dosage; Imatinib Mesylate - adverse effects; Inhibitor drugs; intermittent; Italy; Laboratories; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Male; Middle Aged; Myeloid leukemia; Older people; Original Research; Patients; Preliminary Data; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Quality of Life; Reverse Transcriptase Polymerase Chain Reaction; Sex Factors; Time Factors; tyrosine kinase inhibitor; Italy; intermittent; tyrosine kinase inhibitor; quality of life; chronic myeloid leukaemia
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.3778

Background Intermittent treatment with TKIs is an option for the great majority (70%–80%) of CML patients who do not achieve a stable deep molecular response and are not eligible for treatment discontinuation. For these patients, the only alternative is to assume TKI continuously, lifelong. Methods The Italian phase III multicentric randomized OPTkIMA study started in 2015, with the aim to evaluate if a progressive de‐escalation of TKIs (imatinib, nilotinib, and dasatinib) is able to maintain the molecular response (MR3.0) and to improve Health Related Quality of Life (HRQoL). Results Up to December 2018, 166/185 (90%) elderly CML patients in stable MR3.0/MR4.0 completed the first year of any TKI intermittent schedule 1 month ON and 1 month OFF. The first year probability of maintaining the MR3.0 was 81% and 23.5% of the patients who lost the molecular response regained the MR3.0 after resuming TKI continuously. Patients’ HRQoL at baseline was better than that of matched peers from healthy population. Women was the only factor independently associated with worse baseline HRQoL (p > 0.0001). Overall, global HRQoL worsened at 6 (p < 0.001) but returned to the baseline value at 12 months and it was statistically significantly worse in women (p = 0.001). Conclusions De‐escalation of any TKI by 1 month ON/OFF schedule maintains the MR3.0/MR4.0 in 81% of the patients during the first 12–24 months. No patients progressed to accelerated/blastic phase, all the patients (23.5%) losing MR3.0 regained the MR3.0 and none suffered from TKI withdrawn syndrome. The study firstly report on HRQoL in elderly CML patients moving from a continuous daily therapy to a de‐escalated intermittent treatment. The 1‐year probability of maintaining the MR3.0 while on intermittent 1 month ON/OFF TKI therapy was 81%. Patients’ QoL at baseline was better than that of matched peers from healthy population. Diarrhea significantly improved at 6 and 12 months (p = 0.022) and fatigue worsened at 6 (p = 0.001) and 12 months (p = 0.022). Overall, global QoL worsened at 6 (p < 0.001) but returned to the baseline value at the 12 months