3-YEARS and Beyond Study Completion Results of the Otpkima Randomized Clinical Trial in Elderly CML Patients

The goal of Treatment Free Remission (TFR) is achievable in no more than 25-30% of patients with Ph+ Chronic Myeloid Leukemia (CML) treated with Tyrosine Kinase Inhibitors (TKIs). Thus, for the great majority of patients, particularly for the elderly, the options are to continue TKI therapy life-long or to enter an intermittent TKI administration, as previously published ( Russo D et al, Blood 2013; Russo et al Blood Adv 2015). The probability of major molecular response (MMR or MR3.0) maintenance while on intermittent 1 month on/1 month off TKI at 1 year is 80%, as reported recently in the first interime analysis of the Italian prospective randomized OPTkIMA trial (Malagola M et al, Cancer Med 2021). This is the second interim report of OPTkIMA trial, in which elderly patients with Ph+ CML in sustained (≥ 2 years) confirmed major molecular response (MMR or MR3.0) or deep molecular response (MR4.0 or deeper) were randomly assigned to receive a FIXED intermittent schedule (1 month on/1 month off) vs a PROGRESSIVE intermittent schedule (1 month on/1 month off for the 1 st year, 1 month on/2 months off for the 2 nd year, 1 month on/3 months off for the 3 rd year). After the 3 rd year, clinicians were free to decide if maintain the intermittent schedule, discontinue TKI or resume TKI daily ( Malagola M et al, Cancer Med 2021). At last follow up, 203 patients are evaluable after randomization (104 FIXED vs 99 PROGRESSIVE). At 3 rd year (end of study protocol), by intention to treat, 28/104 (27%) and 45/99 (45%) patients discontinued OPTkIMA because of MR3.0 loss in the FIXED vs PROGRESSIVE arm, respectively (p=0.005). The percentages of patients who discontinued OPTkIMA because of MR3.0 loss at 1 st, 2 nd and 3 rd year in the FIXED vs PROGRESSIVE arm were: 24% in both arms (p=0.97), 1% vs 22% (p=0.001) and 3% vs 15% (p=0.01), respectively (Figure 1). The probability of survival without MR3.0 loss at 1, 2 and 3 years in the FIXED vs PROGRESSIVE arm were: 81%, 69% and 66% vs 81%, 59% and 53%, respectively (Figure 2; p=0.13). None of the patients who lost MR3.0 progressed to accelerated or blastic phase (AP/BP) and all of the patients regained the MR3.0 after continuous TKI resumption within 9 months. At the end of the 3 rd year from randomization, 61/104 (59%) and 36/99 (36%) patients were in MR3.0 or deeper response in the FIXED vs PROGRESSIVE arm, respectively (p=0.001). For these patients, comparing the two arms, Clinicians' choice was to maintain the ongoing