Both Hemant and Francisco make excellent points. The teaching message here is that with all the drugs available, nothing is all or none in terms of adverse events/slide effects. If you look at the original Gleevec/Glivec product monograph for example, pleural effusions are described. Look at studies and monographs and you will find pancreatitis listed. Everything is relative. I would agree with the logic that nilotinib and ponatinib are the least desirable options and that imatinib and to a lesser extent bosutinib are the best choices, but the patient needs to watched very closely on starting anything.


(case repeated here for reader reference)
I have a 52 y.o. male with newly dxed CML. A little over 1 wk. after starting Sprycel 100 mg qday his WBC is dropping nicely, but he has developed abdominal pain with a lipase of approx 7500 and an amylase of nearly 1000. A CT scan of abd/pelvis is c/w acute pancreatitis. There are no prior known risk factors for this complication, though a GI physician is being consulted. I am holding Sprycel pending rcovery from the pancreatitis, but any thoughts regarding rechallenging the pt. with the same dose vs. lowering the dose vs. substituting a different TKI?

Many thanks!

Dear colleague,

Pancreatitis is unusual under dasatinib. However, if there are not other contributing causes, I would think that the drug is clearly the trigger of this complication. Since there has been acute pancreatitis, and not just lipase or amylase increase, I would not rechallenge the patient with dasatinib. I would not try Nilotinib either, given the strong association of this drug with pancreatic abnormalities. Ponatinib is not available but if available it would be other TKI to avoid in case of pancreatitis. Therefore, after the resolution of the pancreatitis I would try imatinib. Bosutinib would be my second choice.

Francisco Cervantes

(case repeated here for reader reference)
I have a 52 y.o. male with newly dxed CML. A little over 1 wk. after starting Sprycel 100 mg qday his WBC is dropping nicely, but he has developed abdominal pain with a lipase of approx 7500 and an amylase of nearly 1000. A CT scan of abd/pelvis is c/w acute pancreatitis. There are no prior known risk factors for this complication, though a GI physician is being consulted. I am holding Sprycel pending rcovery from the pancreatitis, but any thoughts regarding rechallenging the pt. with the same dose vs. lowering the dose vs. substituting a different TKI?

Many thanks!

DEAR HOWARD,
THANK YOU FOR POSTING THIS INTERESTING PROBLEM.
PANCREATITIS WITH DASATINIB IS MUCH LESS COMMON AS COMPARED TO WITH NILOTINIB. SUGGEST YOU RULE OUT OTHER CONTRIBUTING CAUSES LIKE HYPERTRIGLYCERIDEMIA/GALL STONE DISEASE/NIDDM ETC. WOULD START DASATINIB AFTER COMPLETE RESOLUTION OF THE PANCREATITIS AND WITH HALF DOSE 950 MG/DAY) WITH CLOSE MONITORING OF PANCREATIC ENZYMES AND ULTRASONOGRAPHY OF THE PANCREAS. WOULD INCREASE TO FULL DOSE OVER 15 DAYS IF NO EVIDENCE OF RECURRENCE OF THE PANCREATITIS. IF THE ENZYMES START INCREASING ON 50 MG/DAY, WOULD CONSIDER CHANGING TO IMATINIB (DEFINITELY NOT NILOTINIB).


(case repeated here for reader reference)
I have a 52 y.o. male with newly dxed CML. A little over 1 wk. after starting Sprycel 100 mg qday his WBC is dropping nicely, but he has developed abdominal pain with a lipase of approx 7500 and an amylase of nearly 1000. A CT scan of abd/pelvis is c/w acute pancreatitis. There are no prior known risk factors for this complication, though a GI physician is being consulted. I am holding Sprycel pending rcovery from the pancreatitis, but any thoughts regarding rechallenging the pt. with the same dose vs. lowering the dose vs. substituting a different TKI?

Many thanks!

I have a 52 y.o. male with newly dxed CML. A little over 1 wk. after starting Sprycel 100 mg qday his WBC is dropping nicely, but he has developed abdominal pain with a lipase of approx 7500 and an amylase of nearly 1000. A CT scan of abd/pelvis is c/w acute pancreatitis. There are no prior known risk factors for this complication, though a GI physician is being consulted. I am holding Sprycel pending rcovery from the pancreatitis, but any thoughts regarding rechallenging the pt. with the same dose vs. lowering the dose vs. substituting a different TKI?

Many thanks!