Four individuals started on nilotinib due to intolerance to imatinib (cytopenia n?=?2, pores and skin rash n?=?2). among those ML303 continuing nilotinib, 54% of individuals responded which included 14 individuals who accomplished CHR and seven who accomplished major molecular response. In the 1st report on use of nilotinib in Indian individuals, we observed a higher incidence of liver toxicity compared to earlier reports. This should be seen the context that all these individuals received nilotinib as second collection therapy. was carried out 6C12 monthly based on individuals response to treatment. The initial encounter with effectiveness and toxicity is definitely reported. Results Patient Characteristics Thirty-seven individuals with ML303 CML [median 46?years (range 17C69); 20 males (54%)] received nilotinib between January 2010 and June 2016 (Table?1). The median duration from analysis of CML and initiation of nilotinib was 5?years (1.1C23.5?years). Nine individuals experienced medical comorbidities like diabetes or hypertension. Table?1 Baseline characteristics total hematological response, total cytogenetic response, major molecular response, accelerated phase, blast crisis phase, imatinib resistance mutation analysis aNilotinib was started at ML303 a dose of 600?mg/day time in all individuals and attempted escalation to 800?mg/day time when tolerated Majority of the individuals started nilotinib due to failure of imatinib (n?=?33, 89%) (Table?2). IRMA data was available for 27/33 individuals (Table?2). Of these, fifteen (55%) individuals experienced a mutation. The commonest mutations were G250E (n?=?3) and M244?V (n?=?2). Others were E255K, Delh361, E281A, F359V, E355G, F359L, E355A, F311L and F317L (one patient each). Four individuals started on nilotinib due to intolerance to imatinib (cytopenia n?=?2, pores and skin rash n?=?2). The ML303 individuals who experienced rash due to imatinib experienced also lost total haematological response (CHR) at the time of initiation of nilotinib. Table?2 Outcomes of switching to nilotinib thead th align=”remaining” rowspan=”2″ colspan=”1″ Reason for switch to nilotinib /th th align=”remaining” rowspan=”2″ colspan=”1″ Total N (%) /th th align=”remaining” rowspan=”1″ colspan=”1″ Responded N (%) /th th align=”remaining” rowspan=”1″ colspan=”1″ No response N (%) /th th align=”remaining” rowspan=”1″ colspan=”1″ Stopped due to toxicity N (%) /th th align=”remaining” rowspan=”1″ colspan=”1″ Result of switching /th th align=”remaining” rowspan=”1″ colspan=”1″ /th th align=”remaining” rowspan=”1″ colspan=”1″ /th /thead Intolerance to imatinib4 (10.8%)4 (100%)0 (0%)0 (0%)Loss of CHR20 (54.1%)14 (70%)4 (20%)2 (10%)BC3 (8%)1 (33%)2 (66%)CNot accomplished CHR2 (5.4%)0 (0%)2 (100%)CLoss of CCR/MMR2 (5.4%)0 (0%)1 (50%)1 (50%)No achievement of CCR/MMR6 (16%)1 (17%)3 (50%)2 (33%) Open in a separate window Twenty-seven individuals (73%) were in chronic phase at the time of initiation of nilotinib, 7 (19%) were in accelerated phase and 3 (8%) in blast problems. Median white cell count at the time of starting treatment with nilotinib was 44,000/mm3 (3100C1,95,000/mm3). Results with Nilotinib (Fig.?1) Open in a separate windowpane Fig.?1 Flowchart showing the individuals included for analysis and their outcomes after start of nilotinib Median duration of exposure to nilotinib among all 37 individuals was 10?weeks (range 1.5C51?weeks). Twenty-three individuals were continuing nilotinib on last follow-up [Median duration 14?weeks (range 4C34?weeks)]. Fourteen individuals halted nilotinib [progressive disease (n?=?8) and intolerance (n?=?6)]. Of the 23 individuals who were continuing nilotinib seven experienced accomplished MMR (30%). Dose of Nilotinib After starting at a dose of 300?mg twice daily, fifteen individuals (40%) required reduction of the dose at some point during the treatment period. After progressive escalation of IkappaB-alpha (phospho-Tyr305) antibody dose, 25 (67%) and 9 (24%) individuals tolerated 600 and 800?mg/day time (400?mg BD) respectively. Three individuals continued nilotinib at reduced doses [400?mg/day time (n?=?1) and 300?mg/day time (n?=?2)]. Toxicity The most common grade 3/4 toxicity was thrombocytopenia (n?=?9, 24%) while neutropenia (n?=?3, 8%) and anaemia (n?=?2, 5%) were less common. Seven individuals (18%) experienced hyperbilirubinemia [grade 3 (n?=?6); grade 2 (n?=?1)]. Hyperbilirubinemia was mainly conjugated and was associated with normal liver enzymes except in one patient. In four individuals, temporary discontinuation led to total resolution and nilotinib could be restarted. One patient experienced nilotinib related pleural effusion which resolved on temporary cessation and later on he could ML303 be re-challenged successfully. Six individuals (16%) permanently discontinued nilotinib due to toxicity [myelosuppression (n?=?3), hyperbilirubinemia (n?=?3)]. Additional toxicities noted were hyperlipidemia in two individuals (5.4%) and renal dysfunction in two individuals.