Race, Rituxmab and relapse in TTP

Author(s): Shruti Chaturvedi1;Ana G. Antun2;Andrew M. Farland3;Ryan Woods3;Ara Metjian4;Yara A. Park5;Gustaaf de Ridder5,6;Briana Gibson5,7;Raj S. Kasthuri8;Darla K. Liles9;Frank Akwaa10;Todd Clover11;Lisa Baumann Kreuziger12,13;J. Evan Sadler14;Meera Sridharan15;Ronald S. Go15;Keith R. McCrae16;Harsh Vardhan Upreti1,17;Angela Liu1;Ming Y. Lim18;Radhika Gangaraju19;X. Long Zheng20;Jay S. Raval21;Camila Masias22;Spero R. Cataland23;Andrew Johnson24;Elizabeth Davis25;Michael D. Evans26;Marshall A. Mazepa25
Source: Blood (2022) 140 (12): 1335–1344
Original Article
Professional photo of Anjan J Patel, MD

Dr. Anjan Patel's Thoughts

Interesting food for thought in this ethnic group regarding TTP.  Large retrospective review of the TTP registry showing that among races there was no variation in mortality, however African-Americans had a reduced RFS in all metrics. Rituximab was not helpful in 1L therapy in any group.  In the 2L setting, Rituximab had a significant RFS benefit in Caucasians but not in African-Americans.  It did not seem that access to care was the driver in reduced RFS.  African-American’s may also have shorter-lived B-cell depletion from CD20-MAb therapy.

KEY POINTS

  • Race affects overall relapse risk and response to rituximab in iTTP.
  • Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab.

ABSTRACT

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.

Author Affiliations

1Department of Medicine, Johns Hopkins University, Baltimore, MD;2Department of Medicine, Emory University, Atlanta, GA;3Department of Medicine, Wake Forest University, Winston-Salem, NC;4Department of Medicine, University of Colorado, Denver, CO;5Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC;6Geisinger Medical Laboratories, Danville, PA;7Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA;8Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC;9Department of Medicine, East Carolina University, Greenville, NC;10Department of Medicine, University of Rochester, Rochester, NY;11St Charles Healthcare, Bend, OR;12Versiti Blood Research Institute, Milwaukee, WI;13Department of Medicine, Medical College of Wisconsin, Milwaukee, WI;14Department of Medicine, Washington University, St Louis, MO;15Department of Medicine, Mayo Clinic, Rochester, MN;15Department of Medicine, Mayo Clinic, Rochester, MN;16Department of Medicine, Cleveland Clinic, Cleveland, OH;17Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA;18Department of Medicine, University of Utah, Salt Lake City, UT;19Department of Medicine, University of Alabama at Birmingham;20Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS;21Department of Pathology, University of New Mexico, Albuquerque, NM;22Baptist Health South Florida, Miami, FL;23Department of Medicine, The Ohio State University, Columbus, OH;24Department of Laboratory Medicine and Pathology and25Department of Medicine, University of Minnesota, Minneapolis, MN;26Clinical & Translational Science Institute, University of Minnesota, Minneapolis, MN; for the United States Thrombotic Microangiopathies Consortium

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