Authors
Tim H. Brummendorf
Universitätsklinikum Aachen, Universitätsklinikum Hamburg-Eppendorf, Aachen & Hamburg, Germany
Tim H. Brummendorf , Carlo Gambacorti-Passerini , Philippe Schafhausen , Hanna Jean Khoury , Andreas Hochhaus , Thomas Kindler , Thomas Fischer , Nadine Besson , Eric Leip , Virginia Kelly , Jorge E. Cortes
Organizations
Universitätsklinikum Aachen, Universitätsklinikum Hamburg-Eppendorf, Aachen & Hamburg, Germany, University of Milan-Bicocca, Monza, Italy, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany, Emory University School of Medicine, Atlanta, GA, Universitätsklinikum Jena, Jena, Germany, Johannes Gutenberg-Universität, Mainz, Germany, Universitätsklinikum Magdeburg, Magdeburg, Germany, Pfizer Global Research and Development, Paris, France, Pfizer Inc., Cambridge, MA, University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: BOS is an oral dual Src/Abl kinase inhibitor with potent activity in Ph+ leukemia.
Methods: Efficacy and safety of BOS 500 mg/d was evaluated in older (≥65 y; n = 119) and younger (<65 y; n = 451) pts in 3 cohorts: chronic phase chronic myeloid leukemia (CP CML) after imatinib (IM; CP2L cohort; n = 287); CP CML after IM + dasatinib (DAS) and/or nilotinib (NIL; CP3L cohort; n = 119); and accelerated/blast phase (AP/BP) CML or acute lymphoblastic leukemia after IM ± DAS and/or NIL (ADV cohort; n = 164).
Results: Baseline events (≥65 y vs <65 y) included respiratory disorders (35% vs 13%), cardiac disorders (29% vs 9%), and diabetes (4% vs 4%). Median baseline medications were 3 (≥65 y) and 5 (<65 y). Median BOS duration was 11 mo and median follow-up was 31 mo for all pts. 80% of ³65 y and 67% of <65 y pts discontinued BOS, including 32% and 18% due to an adverse event (AE; most commonly thrombocytopenia [6% vs 3%]). Rates of response were similar or lower in older versus younger pts (Table). On-treatment transformation to AP/BP CML was similar between groups. Incidences of nonhematologic treatment-emergent AEs were generally similar between older and younger pts, notably (all grades/grade ≥3 for ≥65 y vs <65 y): diarrhea (85%/9% vs 81%/8%), infection (56%/15% vs 49%/10%), and edema (8%/0% vs 4%/<1%). Common grade ≥3 lab abnormalities (≥65 y vs <65 y) were thrombocytopenia (35% vs 35%), neutropenia (21% vs 25%), and anemia (19% vs 19%).
Conclusions: BOS demonstrated similar efficacy and acceptable safety in both older and younger pts across Ph+ leukemia cohorts.
|
CP2L
|
CP3L
|
ADV
|
|
≥65 y |
<65 y |
≥65 y |
<65 y |
≥65 y |
<65 y |
na |
63 |
223 |
25 |
92 |
29 |
122 |
MHR |
- |
- |
- |
- |
28% |
30% |
CHR |
81% |
87% |
72% |
74% |
14% |
25% |
2-y probability of maintaining CHRb |
67% |
75% |
65% |
69% |
75% |
54% |
na |
61 |
204 |
22 |
88 |
26 |
116 |
MCyR |
43% |
57% |
27% |
34% |
23% |
32% |
CCyR |
38% |
45% |
23% |
24% |
19% |
22% |
2-y probability of maintaining MCyRb |
73% |
74% |
83% |
56% |
20% |
31% |
n |
63 |
224 |
26 |
93 |
30 |
134 |
Transformation to AP/BP |
3% |
5% |
4% |
4% |
4% |
3% |
2-y probability of survivalb |
87% |
92% |
80% |
85% |
43% |
46% |
Abbreviations: MHR, major hematologic response; CHR, complete hematologic response; MCyR, major cytogenetic response; CCyR, complete cytogenetic response.
aEvaluable pts had received ≥1 dose of BOS and a valid baseline assessment.
bKaplan-Meier estimate.