Interview with Meghan Sise, MD: Renal Toxicities with Immune Checkpoint Inhibitors

The Severe Immunotherapy Complications (SIC) Service and Clinical-Translational Research Effort at Mass General Cancer Center is working to address the urgent need to understand how and why immune-related adverse events (irAEs) occur. SIC's multidisciplinary team comprises more than 50 individuals across 19 areas of the hospital, and this unique group of clinicians and researchers are involved in the care of every patient admitted with a suspected irAE after checkpoint blockade immunotherapy.

In this new interview series, Kerry Reynolds, MD, director of the SIC service, sits down with a SIC team member for a deeper-dive into their work. This month we meet Meghan Sise, MD, director of onconephrology at Mass General Hospital, and the nephrologist in the Severe Immunotherapy Complications Service. She has extensive experience looking at clinical predictors and urinary biomarkers of acute kidney injury, and has brought that expertise to bear in order to understand how immune checkpoint inhibitor (ICI) therapy affects kidney function.

Kerry: Meghan, thank you so much for joining us today. We really enjoyed your recent talk that you gave during the Severe Immunotherapy Complications Service seminar series. You and your research team have been doing very interesting work. The recent paper in JITC looking at the rapid corticosteroid taper versus standard of care for immune checkpoint inhibitor induced nephritis was really fantastic. It is so critical to examine the evidence base and look for alternate strategies when it comes to treatment. Can you tell us more about it?

Meghan: In our clinical practice, Dr. Harish Seethapathy and I were noticing that the vast majority of patients with ICI-nephritis were rapidly recovering when we gave them high-dose steroids and withheld other medications that may cause kidney injury. Additionally, a multi-center study confirmed that refractory nephritis is very rare. So, we decided to give shorter steroid tapers to decrease exposure and side effects of steroids, and also allowed oncologists to consider ICI rechallenge sooner. This paper compared how the patients on our “rapid-taper” did compared to a historical control group who received longer 4-6 week courses of steroids.

Kerry: How do you think this work informs the field moving forward? What should we do differently when thinking about steroids for treatment of irAE?

Meghan: The dose and duration of steroids should be individualized to the toxicity; whereas nephritis is very steroid sensitive, other toxicities are commonly resistant to steroids. Subspecialty consultants can help guide oncologists based on what is known about that organ condition. For example, it's well known that acute interstitial nephritis (the same kidney lesion that ICIs cause) generally only requires a short course of steroids and even in some cases can resolve on its own with withdrawal of the offending medication. Where possible, we need to try to create treatment guidelines that are evidence based. More prospective studies are needed.

Kerry: What is the most pressing need, in your opinion, in the field of immune-related adverse events. In short, where do we go from here?

Meghan: We need to predict who will get an irAE and “move on” (i.e. continue therapy and not have morbidity and mortality from their irAE), and who will get an irAE and suffer from either refractory or relapsing disease. We need immune cell biomarkers to identify who will have this “bad” course when they develop an early irAE (thyroiditis, rash, diarrhea), and who should push ahead.

Kerry: Is there any paper in press that we should know about? When/where will it be coming out?

Meghan: As ICI use becomes more widespread, in particular extending to earlier lines of therapy and adjuvant therapy for early stage cancers, there are expected to be rising numbers of long-term survivors exposed to ICIs. We are now studying the more indolent effects of ICIs on organ function, and have recently published a report that details the high rates of new-onset chronic kidney disease and 30% kidney function decline (measured by estimated glomerular filtration rate) among cancer survivors exposed to ICIs.

Publications:

Lee MD, Seethapathy H, Strohbehn IA, Zhao SH, Boland GM, Fadden R, Sullivan R, Reynolds KL, Sise ME. Rapid corticosteroid taper versus standard of care for immune checkpoint inhibitor induced nephritis: a single-center retrospective cohort study. J Immunother Cancer. 2021 Apr;9(4):e002292. doi: 10.1136/jitc-2020-002292.

Chute DF, Zhao S, Strohbehn IA, Rusibamayila N, Seethapathy H, Lee M, Zubiri L, Gupta S, Leaf DE, Rahma O, Drobni ZD, Neilan TG, Reynolds KL, Sise ME. Incidence and Predictors of CKD and Estimated GFR Decline in Patients Receiving Immune Checkpoint Inhibitors. Am J Kidney Dis. 2021 Jun 23:S0272-6386(21)00693-4. doi: 10.1053/j.ajkd.2021.05.012.