Practice Patterns of SGLT2 Inhibitor Use in Stem Cell Transplantation and CART Cell Therapy: A Study from the EBMT Transplant Complications Working Party

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Introduction: Sodium-glucose cotransport protein 2 inhibitors (SGLT2i) have been approved for type 2 diabetes mellitus, chronic heart failure and chronic renal insufficiency. Given treatment- and age-related occurrence of these frequent conditions, SGLT2i are increasingly used in patients with hematological malignancies. No guidelines or clinical recommendations exist on how to manage SGLT2i in the setting of cellular therapies. As a first approach to address this medical need, we aimed to better understand the current clinical practices of the use of SGLT2i in patients undergoing cell therapy, such as autologous (auto) hematopoietic stem cell transplantation (HSCT), allogeneic (allo) HSCT or CAR T-cell therapy (CART). Methods This cross-sectional survey-based study was carried out among all EBMT member centers. Program directors or their designees participated in the survey between March and May 2024. The survey comprised three parts focusing on SGLT2i use in autoHSCT, alloHSCT and CART respectively. Results: There were 103 responding centers (response rate 23.3%) from 39 countries. The majority (69.9%) were of EU origin. Most participating centers performed autoHSCT (98.1%) and to a lesser extent alloHSCT (79.2%) and CART (58.6%). In autoHSCT (n=101), continuation of SGLT2i regardless of emerging clinical events was reported in 51 (51.5%) of centers; discontinuation in case of certain conditions (e.g. acute kidney injury, keto acidosis, sepsis or mucositis) was noted in 32 (32.3%), while 16 (16.2%) of the centers withheld SGLT2i medication prior to start of chemotherapy. In centers experienced with SGLT2i use during autoHSCT, adverse events related to SGLT2i were reported by three centers (3.6%), consisting of urinary tract infections reported by two centers, one of those centers also reported hypoglycemia, additionally one center reported low blood pressure, leading to either cessation or dose reduction (considered by one center) of SGLT2i. Initiation of SGLT2i in eligible autoHSCT patients was only reported to be current practice in seven (7.1%) centers. In alloHSCT (n=80), continuation of SGLT2i was reported in 33 (42.9%) of centers; discontinuation in case of certain conditions (e.g. acute kidney injury, keto acidosis, sepsis, mucositis) was noted in 24 (31.2%), while 20 (26%) of the centers withheld SGLT2i medication regardless of complications prior to start of chemotherapy. In centers experienced with SGLT2i use during alloHSCT, three centers (5.3%) reported adverse events related to SGLT2i, comprising genital fungal infections and urinary tract infections, keto acidosis or low blood pressure, each reported by one different center, and leading to cessation or consideration of dose reduction (one center) of SGLT2i. Initiation of SGLT2i in eligible alloHSCT patients was only reported to be current practice in seven (8.9%) centers. In CART (n=58), continuation of SGLT2i was reported in 30 (52.6%) of centers; discontinuation in case of certain conditions (e.g. acute kidney injury, keto acidosis, sepsis, mucositis, CRS/ICANS) was noted in 17 (29.8%), while 10 (17.5%) of the centers withheld SGLT2i medication regardless of complications prior to start of chemotherapy. In centers experienced with SGLT2i use during CART, adverse events related to SGLT2i were reported by only one center (2.1%), consisting of low blood pressure with subsequent cessation of SGLT2i. Initiation of SGLT2i in eligible CART patients was only reported to be current practice in four (6.9%) centers. Conclusion: Our survey demonstrates that the management of SGLT2i during cellular therapies differs significantly in between the centers. Roughly half of the centers continue SGLT2i during cell therapy while the others either stop it a priori or upon occurrence of adverse events. Of note, less than 10% of the centers reported to initiate treatment in patients meeting indication for SGLT2i. Conversely, data regarding organ protection in patients treated with SGLT2i during stem cell transplantation or CART will be of interest. Our data shows that real-world data on the use of SGLT2i during cellular therapies is required and underlines the need for practice guidelines about when to initiate or stop SGLT2i in this setting.

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