Dasatinib is a second generation TK inhibitor active in CML resistant and/or intolerant to imatinib. Data on efficacy and safety profile in “very elderly”patients (age >75 yrs) are scanty. We studied 28 patients with CP-CML treated with dasatinib when aged >75 yrs at 16 Centers. Median age at diagnosis was 72.3 yrs (IR 62.8-83.9). Male/female ratio was 1.33 (M=16, F=12); Sokal risk was calculated in 20/28 cases (low risk n=4, intermediate n=12, high n=4). Twenty-four patients (85.7%) received a treatment before imatinib. Imatinib starting dose was 400 mg/day in 21 cases (75%) and median period of therapy was of 36.6 months (IR 2.8- 71.3). Cause of imatinib failure was primary resistance in 15 patients (53.6%), secondary resistance in 11 (39.3%) and intolerance in 2 (7.1%). Median age at dasatinib start was 79.3 years (IR 75.0-76.5), with a median time from diagnosis of 76.4 months (IR 4.7 - 173.9). Eleven patients (39.3%) have received a second-line treatment after imatinib stop. Baseline BCR/ABL mutational status was evaluated in 11 cases: 4 displayed no mutation; 3 cases had M244V; M315T, E494G, V299L were present in 1 case each; 1 case presented M351T and F317L. Twenty-three patients had at least one co-morbidity, and median number of concomitant medicaments was 3.5 (IR 1-11). Dasatinib was started at 140 mg/day in 12/28 cases (42.8%), 100 mg in 8 (28.6%), ≥50 mg in 8 (28.6%). After a median treatment period of 18.1 months (IR 0.9-39.8 ), grade 3-4 toxicity was evaluated: 5/28 patients (17.8%) showed hematological toxicity (140 mg n=2; 100 mg n=1; 50 mg n=2); 11 (39.3%) extra-hematological toxicity (140 mg n=6, 100 mg n=2, 50 mg n=3). Seven patients (25%) presented serosal effusions (SE): WHO grade 1-2 in 5 cases (17.8%; 4 cases 140 mg, 2 cases 50 mg); grade 3-4 in 2 (7.1%) (1 case 140 mg, 1 case 50 mg). Sixteen patients (57.1%) underwent dose reduction: of the patients treated with 140 mg (n=12), 11 had a dose reduction vs. 5 reductions in the 16 cases receiving ≤100 mg (P=0.005). Nine patients discontinued dasatinib for ≤6 weeks, while 7 (25%) permanently discontinued therapy: 3 (10.7%) due to drug-related toxicity (n=1 with 100 mg and gastrointestinal toxicity; n=2 with 50 mg and SE, grade 2 and grade 3 respectively), 4 (14.3%) for emergency of a T315I mutation, after a median of 11 months of treatment. Response to treatment was assessable in 24/28 patients (85.7%): 14 (53.8%) had a cytogenetic response (CCyR in 9 cases, PCyR in 3 and minCyR in 2); of these, 5 attained also a molecular response. Nine patients (57.5%) reached at least a complete hematological remission. One case (4.1%) was resistant. The mean Overall Survival and Event Free Survival of the whole cohort were 24.2 and 14.3 months respectively. The present analysis shows that dasatinib may have a major role in the treatment of very elderly patients resistant/intolerant to imatinib; moreover dasatinib 100 mg showed great efficacy and a favorable safety profile in pretreated patients.
EFFICACY AND SAFETY PROFILE OF DASATINIB IN A SUBSET OF VERY ELDERLY PATIENS WITH CHRONIC MYELOID LEUKEMIA (CML) RESISTANT/INTOLERANT TO IMATINIB
CAVAZZINI, Francesco;SACCENTI, Elena;
2010
Abstract
Dasatinib is a second generation TK inhibitor active in CML resistant and/or intolerant to imatinib. Data on efficacy and safety profile in “very elderly”patients (age >75 yrs) are scanty. We studied 28 patients with CP-CML treated with dasatinib when aged >75 yrs at 16 Centers. Median age at diagnosis was 72.3 yrs (IR 62.8-83.9). Male/female ratio was 1.33 (M=16, F=12); Sokal risk was calculated in 20/28 cases (low risk n=4, intermediate n=12, high n=4). Twenty-four patients (85.7%) received a treatment before imatinib. Imatinib starting dose was 400 mg/day in 21 cases (75%) and median period of therapy was of 36.6 months (IR 2.8- 71.3). Cause of imatinib failure was primary resistance in 15 patients (53.6%), secondary resistance in 11 (39.3%) and intolerance in 2 (7.1%). Median age at dasatinib start was 79.3 years (IR 75.0-76.5), with a median time from diagnosis of 76.4 months (IR 4.7 - 173.9). Eleven patients (39.3%) have received a second-line treatment after imatinib stop. Baseline BCR/ABL mutational status was evaluated in 11 cases: 4 displayed no mutation; 3 cases had M244V; M315T, E494G, V299L were present in 1 case each; 1 case presented M351T and F317L. Twenty-three patients had at least one co-morbidity, and median number of concomitant medicaments was 3.5 (IR 1-11). Dasatinib was started at 140 mg/day in 12/28 cases (42.8%), 100 mg in 8 (28.6%), ≥50 mg in 8 (28.6%). After a median treatment period of 18.1 months (IR 0.9-39.8 ), grade 3-4 toxicity was evaluated: 5/28 patients (17.8%) showed hematological toxicity (140 mg n=2; 100 mg n=1; 50 mg n=2); 11 (39.3%) extra-hematological toxicity (140 mg n=6, 100 mg n=2, 50 mg n=3). Seven patients (25%) presented serosal effusions (SE): WHO grade 1-2 in 5 cases (17.8%; 4 cases 140 mg, 2 cases 50 mg); grade 3-4 in 2 (7.1%) (1 case 140 mg, 1 case 50 mg). Sixteen patients (57.1%) underwent dose reduction: of the patients treated with 140 mg (n=12), 11 had a dose reduction vs. 5 reductions in the 16 cases receiving ≤100 mg (P=0.005). Nine patients discontinued dasatinib for ≤6 weeks, while 7 (25%) permanently discontinued therapy: 3 (10.7%) due to drug-related toxicity (n=1 with 100 mg and gastrointestinal toxicity; n=2 with 50 mg and SE, grade 2 and grade 3 respectively), 4 (14.3%) for emergency of a T315I mutation, after a median of 11 months of treatment. Response to treatment was assessable in 24/28 patients (85.7%): 14 (53.8%) had a cytogenetic response (CCyR in 9 cases, PCyR in 3 and minCyR in 2); of these, 5 attained also a molecular response. Nine patients (57.5%) reached at least a complete hematological remission. One case (4.1%) was resistant. The mean Overall Survival and Event Free Survival of the whole cohort were 24.2 and 14.3 months respectively. The present analysis shows that dasatinib may have a major role in the treatment of very elderly patients resistant/intolerant to imatinib; moreover dasatinib 100 mg showed great efficacy and a favorable safety profile in pretreated patients.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
