Abstract: SA-PO224
Atypical Hemolytic Uremic Syndrome (aHUS)/TMA in Genetically Predisposed Patients Treated with a Novel Agent for Relapsed/Refractory Multiple Myeloma
Session Information
- Onconephrology: Immunological Cross-Talk
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Gosai, Jiten, The University of Texas Health Science Center at Houston, Houston, Texas, United States
- Alobaidi, Demah, Baylor College of Medicine, Houston, Texas, United States
- Al Shaarani, Majd, The University of Texas Health Science Center at Houston, Houston, Texas, United States
- Tchakarov, Amanda, The University of Texas Health Science Center at Houston, Houston, Texas, United States
- Mandayam, Sreedhar A., UT MD Anderson Cancer Center, Houston, Texas, United States
Introduction
A number of therapies are being studied to treat relapsed/refractory multiple myeloma (RRMM). Modakafusp alfa (TAK-573) is a novel candidate for treating RRMM. It is a first-in-class immunocytokine that delivers interferon alpha-2b (IFNα2b) to CD38+ cells, showing promising anti-myeloma activity.
Case Description
Here we present two adult males, ages 46 (Patient 1) & 56 (Patient 2) seen at MD Anderson Cancer Center, both with history of RRMM & enrolled in clinical study 2022-0497 G2A4 carfilzomib and modakafusp alfa. Both presented with oliguric AKI requiring RRT, new-onset thrombocytopenia, schistocytosis & transaminitis with elevated LDH. Both had genetic testing & kidney biopsy while admitted. Patient 1 is heterozygous for the extended CFH-H3 risk haplotype, consistent with increased risk for development/progression of atypical hemolytic uremic syndrome (aHUS). The kidney biopsy showed acute/active thrombotic microangiopathy (TMA)-like changes. Patient 2 is heterozygous for a CFHR1-3 deletion (strongly suggesting a large contiguous deletion of both CFHR1 and 3 genes). Patient 2’s kidney biopsy also showed findings consistent with TMA features. Both patients had hemodialysis & eculizumab while inpatient & are continuing on hemodialysis on an outpatient basis.
Discussion
Both patients were recently started on carfilzomib & modakafusp alfa, a relatively new phase I/II clinical trial. Preliminary results from 2021 show modakafusp alfa caused side effects such as neutropenia, thrombocytopenia & mild reactions post-infusion. aHUS/TMA with AKI from modakafusp alfa has not previously been reported to our knowledge. Case reports of aHUS/TMA from carfilzomib do exist, however. We conclude that it is reasonable to perform genetic testing prior to initiating treatment with modakafusp alfa +/- carfilzomib, to mitigate the risk of aHUS/TMA as seen in our two patients.