In an interview with Pharmacy Times, professor of drugs Nelson Leung, MD, marketing consultant of each the Division of Nephrology and Hypertension in addition to the Division of Hematology, Department of Internal Medicine, notes the significance of understanding and managing kidney illnesses related to hematologic malignancies and drug therapies. Leung additionally highlights developments in therapy and potential analysis instructions. He will probably be presenting on the panel “Thrombotic Microangiopathy: Drugs and Cancer” throughout ASN Kidney Week in Philadelphia, Pennsylvania (November 2, 2023, to November 5, 2023).

Pharmacy Times: What medication and most cancers varieties are identified to trigger thrombotic microangiopathy (TMA), and the way do they manifest by way of kidney well being?

Nelson Leung: That’s an excellent query. There are literally various totally different most cancers varieties that may trigger TMA; nonetheless, the most typical ones are the mucin-producing cancers, equivalent to these from the GI tract or breast most cancers. In phrases of medication, various totally different medication have been related to TMA. The most typical most cancers drug is gemcitabine. Now, sadly, gemcitabine is utilized in various totally different most cancers varieties, so you may see that it is really quite common due to that.

Another class of medication that’s generally related to TMA is the vascular endothelial development issue (VEGF) inhibitors and the a number of tyrosine kinase inhibitors. These have a direct mechanism of inflicting kidney harm and TMA by means of disruption of VEGF.

Another class of medication that’s now generally seen inflicting TMA is the proteasome inhibitors used to deal with a number of myeloma, and notably of the three proteasome inhibitors—ixazomib, bortezomib, and carfilzomib—carfilzomib appears to be the 1 that’s inflicting a lot of the TMAs. And then lastly, there are miscellaneous medication, equivalent to interferon and ticlopidine, that may additionally trigger drug-induced TMA.

Pharmacy Times: Leukemias and lymphomas are talked about as causes for varied kidney lesions. Can you present examples of renal problems that may come up from these hematologic malignancies, and the way these kidney-related points could current in sufferers?

Leung: Kidney involvement is definitely not unusual in sufferers with leukemia and lymphomas. Typically, in leukemias, the complication is thru direct infiltration of the leukemia into the kidneys. In lymphoma, the causes of kidney harm [are] extra complicated. Certainly, direct infiltration can also be seen, however in contrast to leukemias, lymphomas can produce monoclonal proteins that may injure the kidney, both by means of deposition—like in monoclonal gammopathy of renal significance—or the monoclonal proteins can activate complement-causing TMA. So, various totally different mechanisms can happen, leading to acute kidney harm (AKI) and these sufferers and these sufferers sometimes current with progressive AKI. It could be delicate at first, however actually, a few of these sufferers can develop fairly AKI ensuing from the TMA or the leukemic and lymphoma infiltration.

Pharmacy Times: What potential developments or analysis instructions do you foresee on this setting, notably in understanding and managing kidney illnesses related to hematologic malignancies and drug therapies? How can these developments additional enhance affected person outcomes and care?

Leung: Yeah, there’s been super advances within the therapy of lymphomas in addition to a number of myeloma. Aside from the newer medication, now there’s immunotherapy with chimeric antigen receptor T-cell remedy, in addition to bispecifics. Both of those therapies tremendously elevated the hematologic response in these sufferers and…for the reason that kidney perform restoration depends on the hematologic response, we should always search larger renal response with the newer therapies.

I feel that along with the development within the hematology world, there are additionally improvement within the glomerular illness world that we will benefit from. Those are issues like complement inhibitors that may assist lower the kidney harm from monoclonal immunoglobulin-induced complement activation, and different renal protecting medication equivalent to SGLT2 inhibitors must be explored in a few of these illnesses as nicely.