Nilotinib in patients with imatinib-resistant or -intolerant chronic myelogenous leukemia in chronic phase (CML-CP): Updated phase II results

Abstract

7010 Background: Nilotinib, a potent and highly selective BCR-ABL inhibitor, has been approved in both the US and Europe for the treatment of patients (pts) with CML-CP and accelerated phase CML (CML-AP) who are resistant or intolerant to prior therapy, including imatinib. Methods: This phase 2, open-label study was designed to evaluate the efficacy and safety of nilotinib in pts with Philadelphia chromosome-positive (Ph+) imatinib-resistant or -intolerant CML-CP. Nilotinib was administered at 400 mg twice daily (BID), with the possibility to dose escalate to 600 mg BID for inadequate responses. The primary endpoint was the rate of major cytogenetic response (MCyR). Results: Included in this analysis were 321 pts (71% imatinib-resistant; 29% imatinib-intolerant). 72% of pts received prior imatinib doses > 600 mg. Of the 206 pts who did not have complete hematological remission (CHR) at baseline, 158 (77%) achieved CHR during nilotinib therapy. Overall, MCyR was observed in 184 pts (57%); 41% had complete CyR. MCyR was observed in 125 (55%) of the 227 imatinib-resistant pts and in 59 (63%) of the 94 imatinib-intolerant pts. The median time to CHR and MCyR was 1.0 and 2.8 months, respectively. The majority of pts (84%) maintained MCyR for at least 18 months. At 18 months, the estimated overall survival rate was 91%. Treatment with nilotinib is ongoing in more than half of pts enrolled. The most frequent grade 3/4 laboratory abnormalities were thrombocytopenia (28%), neutropenia (30%), and asymptomatic serum lipase elevation (15%). Grade 3/4 non-hematologic AEs were rare and included rash, headache, and diarrhea. A low incidence of QT prolongation (QTcF > 500 msec, < 1%) was observed overall. The safety profile of nilotinib has not changed with increased follow up. There was minimal cross-intolerance between nilotinib and imatinib in pts intolerant to prior imatinib treatment. Conclusions: The present study confirms that nilotinib induces significant and durable responses in CML- CP pts with imatinib-resistance or -intolerance. Nilotinib is well tolerated, with minimal occurrence of grade 3/4 AEs and minimal cross-intolerance to imatinib, and is a valuable new treatment option for this pt population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Bristol-Myers Squibb, Novartis Bristol-Myers Squibb, Novartis Bristol-Myers Squibb, Innovive, Merck, Novartis, Wyeth