Nilotinib 300 Mg Twice Daily Is Effective and Well Tolerated as First Line Treatment of Ph-Positive Chronic Myeloid Leukemia in Chronic Phase: Preliminary Results of the ICORG 0802 Phase 2 Study.
Authors: O'Dwyer Michael C , Kent Emma , Parker Michael , Swords Ronan T. , Giles Frank , Coutre Philipp le , Padmanabhan Swaminathan , Moulton Brian , McMullin Mary Frances , Langabeer Stephen , Egan Karine , Conneally Eibhlin 
Published: October 2019

Abstract
Abstract 3294
Poster Board III-1
Imatinib (IM) 400 mg daily is currently the standard treatment for early chronic phase (ECP) CML. Nilotinib, a more potent, second generation Abl inhibitor, is highly effective in IM resistant patients and two recent phase II trials have demonstrated impressive activity of nilotinib 400mg BID in ECP. Given the relatively favourable prognosis of this population with IM 400mg alone, any significant increase in toxicity compared to IM could be problematic. Thus, while initial results with nilotinib 400mg BID have been very encouraging, we wished to explore a lower dose schedule, 300mg BID, believing this could be equally effective but with the potential for fewer adverse events, such as lipase and bilirubin elevations and QT prolongation. To investigate the safety and efficacy of nilotinib 300 mg BID in untreated, ECP, Ph-pos CML patients, ICORG, the All-Ireland Cooperative Oncology Research Group is conducting an open-label, single stage, multicenter, phase II study (ClinicalTrials.gov NCT00809211). The primary endpoint is the CCyR rate at 6 months; secondary endpoints include the kinetics of molecular response, determined by Q-PCR at baseline and 3 monthly from start of treatment. To date, 15 patients have been enrolled on the trial. The median age is 56 (range 26 –77); 47% have low risk Sokal score, 20% intermediate and 33% high risk. Median follow up is currently 70 days (range 10–250).

RESULTS:
At 3 months 5 patients are evaluable for response: the CHR rate is 100%, the CCyR is 80% and MMR rate is 60%. No patient in the cohort (n=15) has progressed on study and there have been no dose escalations. The median daily dose was 415mg (range 261–600mg n=15); 5/15 interrupted nilotinib at least once with a median duration of interruption of 6 days. The dose of nilotinib at the last visit was 300mg BID in 11/15 patients (73%) and 200mg BID in 4/15 patients (27%). There was no grade III/IV haematologic toxicity. Grade III non-haematologic toxicity included an elevated lipase in 3/15 (20%). The only other grade III toxicity noted was musculo-sleketal pain in 1 patient. There were no grade IV toxicities.

CONCLUSION:
In this preliminary analysis, nilotinib 300mg BID induces high rates of CCyR. The current results are similar to those previously reported with nilotinb 400mg BID with less haematolgic toxicity noted but with haematologic, cytogenetic and molecular responses occuring within 3 months.

Disclosures:
Off Label Use: Nilotinib 300mg bid for newly diagnosed CML . Giles:Merck: Research Funding; BMS: Research Funding; Novartis: Research Funding; Millenium: Research Funding. le Coutre:BMS: Honoraria; Novartis: Honoraria. McMullin:BMS: Honoraria; Novartis: Honoraria. Egan:Novartis: Employment. Conneally:BMS: Honoraria; Novartis: Honoraria.