I have a 75-year-old man with new diagnosis of AML, with 80% blast on bone marrow. He presented with pancytopenia and anemia not getting better with B12 supplementation. He has past medical history of CKD stage 3 GFR 30-59 with proteinuria 400 to 700 mg, suspected hypertensive/diabetic nephropathy, progressive renal function decline in the past month with creatinine increasing into the low threes. He is currently day 7 of azacytidine and venetoclax. On day 1, his creatinine was 4 and now it is 3.65 He has BUN of 100 since day 1. Nephrology noted he has proteinuria, 3g in urine now. Admission labs showed possible TLS (Uric acid 5.7, K 6, Ca 8, Phos 5.7, creatiine of 4) for which he got rasburicase and decrease in UA but renal function did not improve. Would you have recommended dose adjustment to Aza or Ven? I did not.
I typically do not reduce the dose of either venetoclax (ven) or azacitidine (aza) during induction for renal dysfunction. Some clinicians recommend a 50% reduction in azacitidine because some of its metabolites are cleared renally. However, pharmacokinetic data do not support such a significant reduction, and the exact dose reduction remains unclear. In this setting, I usually opt for decitabine, as it has no renal clearance, eliminating the need for guesswork. The phase II study prior to VIALE-A, decitabine and venetoclax (dec/ven) was also included as a treatment arm and although not designed or powered, it showed similar efficacy to aza/ven. As for venetoclax, it is hepatically cleared, so no adjustments are needed for renal dysfunction. We typically do not administer venetoclax for 28 days due to the risk of prolonged cytopenias. Instead, we opt for a 21-day cycle or, at the very least, obtain an aplasia marrow between days 21 and 28. If the marrow is aplastic, we hold therapy; if residual leukemia is present, we proceed to the next cycle. With all of this in mind, I would not have changed your approach to induction. Going forward, if the patient achieves CR, I would base the dosing on their blood counts. If they attain CR but do not recover their counts within a reasonable time frame, I would consider reducing the venetoclax to a 21-day cycle (or even a 14-day cycle) to see if that alleviates the myelosuppression. If count recovery is still significantly delayed, I would then consider reducing the azacitidine dose, starting with a 25% reduction. There is no absolute right answer here, and many reasonable approaches exist.
