ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

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

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.