(PA-401) Intensified Cyclophosphamide, Bortezomib, Dexamethasone (iCyBorD) for the treatment of newly diagnosed Multiple Myeloma with Acute Kidney Injury

There is no standard treatment for newly diagnosed multiple myeloma (NDMM) presenting with acute kidney injury (AKI). The MYRE trial noted no additive benefit of bolus cyclophosphamide (Cy) to bortezomib (Bor) and dexamethasone (D) for NDMM and cast nephropathy not requiring dialysis. A retrospective study demonstrated daratumumab’s (dara) efficacy in NDMM with AKI, though dara isn’t universally available in this setting. We report the outcomes of treatment with lower dose, hyperfractionated Cy with CyBorD (iCyBorD) in NDMM patients with AKI.

Methods:   

This retrospective study included adults with NDMM and AKI between 1/1/14 and 1/1/24 at the University of California, Davis. Patients received iCyBorD (Cy 250mg/m² every 12 hours for 4 doses, Bor 1.3 mg/m2 days 1, 4, 8, 11, D 20 or 40 mg day 1-4,8-11) followed by imid based therapy after 1 cycle, standard weekly (w)CyBorD, or a non-CyBorD regimen. The primary endpoints were IMWG defined overall renal response (ORR), and time to initial and best renal response. Secondary endpoints included MM response and toxicity.

Results:   

68 patients were included: 12 each received iCyBorD, wCyBorD, and dara based regimens with 32 treated with non-dara treatments. Baseline eGFR was similar in the iCyBorD and wCyBorD groups and higher in non-CyBorD patients. ORR rates with iCyBorD of 92% (n=11) were superior to responses with dara and other non-dara regimens at 42% (n=5) and 44% (n=14), respectively (p= 0.0272; p=0.0057). wCyBorD resulted in 75% (n=9) ORR rate. iCyBorD resulted in a median time to initial renal response of 11 vs 64 days with dara based treatments (p=0.04). Time to initial renal response with wCyBorD and non-dara regimens were 38 and 37 days, respectively. Time to best renal response was comparable at a median of 26, 44, 64, and 37 days with iCyBorD, wCyBorD, dara and non-dara based regimens, respectively (P=0.16). After 1 cycle, eGFR improvement in the iCyBorD group was 162% compared to 46%, 19%, and 19% in the wCyBorD, dara and non-dara groups, respectively.

Time to best myeloma response was comparable amongst all groups: median of 45, 83, 66, and 85 days with dara, non-dara, iCyBorD, and wCyBorD regimens, respectively (p=0.21).

Among those treated with iCyBorD, 5 (42%) grade (G) 3 neutropenia, 1 (8%) G 3 thrombocytopenia and a 1 gastric ulcer perforation events occurred. No instances of neutropenic infections were noted. Among wCyBorD patients: 1(8%) each G3 neuropathy, and pancreatitis events occurred. Among dara treated patients, 2 (17%) G3 neutropenia, and 1 (8%) lung infection events occurred. Among non-dara treated patients, 3 (9%) G3 neutropenia, and 1 (3%) G3 thrombocytopenia events occurred.  

Conclusions:   

One cycle of iCyBorD was effective at inducing rapid renal responses while yielding similar toxicity profiles to other regimens. iCyBorD is an effective treatment for NDMM presenting with AKI, and may be considered in settings where dara is unavailable.