A Prospective Carfilzomib-Based Desensitization Trial: Phase 1 Results.

S. Tremblay,¹ A. Shields,¹ R. Alloway,¹ P. Brailey,¹ B. Abu Jawdeh,¹ T. Latif,¹ J. Driscoll,¹ M. Pando,² A. Girnita,¹ E. Woodle.¹

¹U Of Cincinnati, Cincinnati
²Mayo Clinic, Phoenix.

Meeting: 2016 American Transplant Congress

Abstract number: 318

Keywords: Alloantibodies, B cells, Kidney, Sensitization

Session Information

Session Name: Concurrent Session: Kidney: Desensitization

Session Type: Concurrent Session

Date: Monday, June 13, 2016

Session Time: 4:30pm-6:00pm

Presentation Time: 4:30pm-4:42pm

Location: Room 304

Carfilzomib (CFZ) is mechanistically distinct from bortezomib as it is an irreversible PI. Results from phase 1 of a CFZ desensitization (DS) trial are presented

Methods: 6 pts each received 12 escalating CFZ doses (20,27,36mg/m²) followed by 3 plasmapheresis. Primary efficacy endpoint is immunodominant antibody (iAb) reduction. HLA antibody (Ab) specificities were defined by single antigen beads (SAB). cPRA was calculated with the OPTN cPRA calculator. Enabled PRA was calculated by entering HLA specificities reduced by DS below a defined MFI level (1500, 4000 of 8000 MFI). High-precision PRA (cPRAd) values were derived using a cPRAd calculator that provided PRA values to several decimals. Number of donors required to match (DRTM) was calculated by: 1/(1-pPRA) and fold decrease in DRTM was defined as (DRTM pre-treatment)/(DRTM post-treatment).

Results: 6 patients completed Phase 1;5/6 patients had a cPRA > 96%. iAb decreases averaged 81.6% at day 53 and 83% had iAb decreases > 80%. iAb values at several time points in a single patient during CFZ treatment alone revealed an iAb decrease of 71%. # of HLA Ab specificities were substantially reduced. Tables 1 and 2 summarize iAb and cPRA results. Figure 1 summarizes # of HLA specificities. Toxicities included 2 grade 1 transaminase elevations and a grade 1 peripheral neuropathy that resolved in 7 days.

ID	iDSA specificity	Pre-treatment iAb Titer	pre-treatment cPRA (%)	D0 iAb MFI	D53 iAb MFI	Reduction iAb (%)
A	DQ7.2,DQ9,DQ7.5	Neat	98	10,330	417	96
B	A31	Neat	58	4022	33	99.2
C	B12 creg	1:32	100	8192	1494	81.8
D	A29,A36	1:64	100	3934	558	85.8
E	B7 creg	1:8	97	5980	3362	42.9
F	A2	1:1024	100	12910	2061	84

Conclusions: CFZ monotherapy provides substantial iAb reductions with minimal toxicities.

CITATION INFORMATION: Tremblay S, Shields A, Alloway R, Brailey P, Abu Jawdeh B, Latif T, Driscoll J, Pando M, Girnita A, Woodle E. A Prospective Carfilzomib-Based Desensitization Trial: Phase 1 Results. Am J Transplant. 2016;16 (suppl 3).

To cite this abstract in AMA style:

Tremblay S, Shields A, Alloway R, Brailey P, Jawdeh BAbu, Latif T, Driscoll J, Pando M, Girnita A, Woodle E. A Prospective Carfilzomib-Based Desensitization Trial: Phase 1 Results. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/a-prospective-carfilzomib-based-desensitization-trial-phase-1-results/. Accessed November 25, 2024.

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