Ajai Chari1, Paul G Richardson2, Dorothy Romanus3, Meletios A Dimopoulos4, Pieter Sonneveld5, Evangelos Terpos4, Roman Hajek6, Aditya Raju7, Antonio Palumbo3, Lauren E Cain3, Marlo Blazer7, Hui Huang3, Eileen Farrelly7, Sikander Ailawadhi8. 1. Department of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 2. Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 3. Global Outcomes Research, Millennium Pharmaceuticals, Inc., A Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA. 4. Hematology & Medical Oncology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece. 5. Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. 6. University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic. 7. Scientific Consulting, Xcenda, Palm Harbor, FL, USA. 8. Division of Hematology/Oncology, Department of Medicine, Mayo Clinic, Jacksonville, FL, United States.
Abstract
Lack of head-to-head trials highlights a need for comparative real-world evidence of proteasome inhibitors plus Rd. Methods: In this retrospective, US population-representative EHR study of RRMM patients initiating IRd, KRd, or VRd in line of therapy (LOT) ≥2 between 1/2014 and 9/30/2018, 664 patients were treated in LOT ≥2 with: IRd, n = 168; KRd, n = 208; VRd, n = 357. Median age was 71/65/71 years; 67%/70%/75% had a frailtymodified score of intermediate/frail; 20%/28%/13% had high cytogenetic risk in I-/K-/V-Rd groups. Risk of PI-triplet discontinuation was lower for I- vs. K-Rd (HR: 0.71) and I- vs. V-Rd (HR: 0.85); unadjusted, median TTNTs (months): 12.7/8.6/14.2 (LOT ≥2) and 16.8/9.5/14.6 (LOT 2-3) (I-/K-/V-Rd). Adjusted TTNT was comparable between I-/K-/V-Rd in LOT ≥2 with a TTNT benefit among intermediate/frail patients for I- (HR: 0.70; P=0.04) and V- (HR: 0.73; P<0.05) vs. K-Rd. I/K/V-Rd triplets were comparable in TTNT overall, but IRd and VRd were associated with longer TTNT in intermediate/frail patients than KRd. The results suggest a trial-efficacy/real-world-effectiveness gap, especially for KRd, underlining the limited generalizability of trial results where >50% of patients are excluded. Individualized treatment based on patient characteristics, such as frailty status, is especially pertinent in an elderly RRMM population.
Lack of head-to-head trials highlights a need for comparative real-world evidence of proteasome inhibitors plus Rd. Methods: In this retrospective, US population-representative EHR study of RRMM patients initiating IRd, KRd, or VRd in line of therapy (LOT) ≥2 between 1/2014 and 9/30/2018, 664 patients were treated in LOT ≥2 with: IRd, n = 168; KRd, n = 208; VRd, n = 357. Median age was 71/65/71 years; 67%/70%/75% had a frailtymodified score of intermediate/frail; 20%/28%/13% had high cytogenetic risk in I-/K-/V-Rd groups. Risk of PI-triplet discontinuation was lower for I- vs. K-Rd (HR: 0.71) and I- vs. V-Rd (HR: 0.85); unadjusted, median TTNTs (months): 12.7/8.6/14.2 (LOT ≥2) and 16.8/9.5/14.6 (LOT 2-3) (I-/K-/V-Rd). Adjusted TTNT was comparable between I-/K-/V-Rd in LOT ≥2 with a TTNT benefit among intermediate/frail patients for I- (HR: 0.70; P=0.04) and V- (HR: 0.73; P<0.05) vs. K-Rd. I/K/V-Rd triplets were comparable in TTNT overall, but IRd and VRd were associated with longer TTNT in intermediate/frail patients than KRd. The results suggest a trial-efficacy/real-world-effectiveness gap, especially for KRd, underlining the limited generalizability of trial results where >50% of patients are excluded. Individualized treatment based on patient characteristics, such as frailty status, is especially pertinent in an elderly RRMM population.
Authors: Evangelos Terpos; Joseph Mikhael; Roman Hajek; Ajai Chari; Sonja Zweegman; Hans C Lee; María-Victoria Mateos; Alessandra Larocca; Karthik Ramasamy; Martin Kaiser; Gordon Cook; Katja C Weisel; Caitlin L Costello; Jennifer Elliott; Antonio Palumbo; Saad Z Usmani Journal: Blood Cancer J Date: 2021-02-18 Impact factor: 11.037
Authors: Thierry Facon; Christopher P Venner; Nizar J Bahlis; Fritz Offner; Darrell J White; Lionel Karlin; Lotfi Benboubker; Sophie Rigaudeau; Philippe Rodon; Eric Voog; Sung-Soo Yoon; Kenshi Suzuki; Hirohiko Shibayama; Xiaoquan Zhang; Philip Twumasi-Ankrah; Godwin Yung; Robert M Rifkin; Philippe Moreau; Sagar Lonial; Shaji K Kumar; Paul G Richardson; S Vincent Rajkumar Journal: Blood Date: 2021-07-01 Impact factor: 25.476
Authors: Sudhir Manda; Habte A Yimer; Stephen J Noga; Saulius Girnius; Christopher A Yasenchak; Veena Charu; Roger Lyons; Jack Aiello; Kimberly Bogard; Renda H Ferrari; Dasha Cherepanov; Brittany Demers; Vickie Lu; Presley Whidden; Suman Kambhampati; Ruemu E Birhiray; Haresh S Jhangiani; Ralph Boccia; Robert M Rifkin Journal: Clin Lymphoma Myeloma Leuk Date: 2020-07-06
Authors: Gordon Cook; A John Ashcroft; Guy Pratt; Rakesh Popat; Karthik Ramasamy; Martin Kaiser; Matthew Jenner; Sarah Henshaw; Rachel Hall; Jonathan Sive; Simon Stern; Matthew Streetly; Ceri Bygrave; Richard Soutar; Neil Rabin; Graham H Jackson Journal: Br J Haematol Date: 2020-06-10 Impact factor: 8.615