Ciltacabtagene Autoleucel, an Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up
CAR-T for myeloma, impressive response rate, overall survival not reached.
Results from the randomized phase III DREAMM-7 study of belantamab mafodotin (belamaf) + bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in relapsed/refractory multiple myeloma (RRMM).
Author(s): Maria-Victoria Mateos1; Pawel Robak2; Marek Hus3; Zhongjun Xia4; Vera Zherebtsova5; Christopher Ward6; P. Joy Ho7; Roman Hajek8; Kihyun Kim9; Meletios A. Dimopoulos10; Claudio Cerchione11; Antonio Riccio12; Astrid McKeown13; Rachel Rogers14; Hena Baig15; Lydia Eccersley16; Sumita Roy-Ghanta17; Joanna Opalinska18; Vania Hungria19
Source: https://doi.org/10.1200/JCO.2024.42.36_suppl.439572
Dr. Maen Hussein's Thoughts
Triplet second line therapy shows superiority over daratumumab bortezomib and dexamethasone. This regimen is now used in first line with lenalidomide in some patients as quadruplet therapy, hence this second line regimen with Blantamab could be a second line option. The eye exam is still a pain and it is also more toxic.
BACKGROUND
Belamaf, a BCMA-targeted antibody drug conjugate, has previously demonstrated clinical activity and a manageable safety profile, supporting its use in combination with standard-of-care (SoC) therapies in RRMM. DREAMM-7 (NCT04246047) is a global, randomized, open-label, phase III head-to-head trial evaluating the efficacy and safety of BVd triplet vs SoC triplet, DVd, in patients (pts) with RRMM with ≥1 prior line of therapy (LOT).
METHODS
Pts with ≥1 prior LOT were randomized (1:1) to BVd: B 2.5 mg/kg IV Q3W + V 1.3 mg/m2 (D1, 4, 8, 11 of 21-day cycles (C); up to 8 C) + d 20 mg (D1, 2, 4, 5, 8, 9, 11, 12; up to 8 C) or DVd: D 16 mg/kg (21-day C), C1-3, Q1W, C4-8, Q3W, and Q4W from C 9 on); V and d schedules were the same. The primary endpoint was independent review committee-assessed progression free survival (PFS). Secondary endpoints available include overall survival (OS), duration of response (DOR), overall response rate (ORR).
RESULTS
494 pts were randomized (BVd n = 243, DVd n = 251). With a median (range) follow-up of 28.2 mo (0.10-40 mo), the median PFS (mPFS) in the BVd arm was 36.6 mo (95% CI, 28.4 mo-NR) vs 13.4 mo (11.1-17.5 mo) with DVd; hazard ratio (HR) 0.41 (95% CI, 0.31-0.53; p < 0.00001). OS data was 29% mature; median OS was not reached in either arm; HR, 0.57 (95% CI, 0.40-0.80; nominal p < 0.0005). ORR was 82.7% (95% CI, 77.4-87.3%) with BVd and 71.3% (65.3-76.8%) with DVd. Median DOR (mDOR) was 35.6 mo (95% CI, 30.5 mo-NR) for BVd vs 17.8 mo (13.8-23.6 mo) for DVd. All pts in both arms experienced ≥1 AE (Table). Grade 3/4 treatment-related AEs (TRAE) were reported in 90% of pts in the BVd arm and 67% with DVd. Serious AEs (SAE) were reported in 50% of pts in BVd vs 37% in DVd arm. Ocular AEs were more frequent on BVd vs DVd (79% vs 29%) and were manageable.
CONCLUSIONS
The DREAMM-7 head-to-head study of BVd vs DVd demonstrated statistically significant PFS benefit of BVd with a mPFS improvement of 23 mo in pts with RRMM with ≥1 prior LOT. A strong and clinically meaningful OS benefit (nominal p < 0.0005) was observed. Additionally, BVd led to greater depth of response and doubling of mDOR vs DVd and had a manageable safety profile. These results support BVd as a potential new SoC in this setting.
Author Affiliations
1Hospital Universitario de Salamanca, Salamanca, Spain; 2Medical University of Lodz, Lodz, Poland; 3Samodzielny Publiczny Szpital Kliniczny, Lublin, Poland; 4Sun Yat-sen University Cancer Center, Guangzhou, China; 5Gorodskaya Klinicheskaya Bol’nitsa Im. S.; Botkina, Moscow, Russian Federation; 6Royal North Shore Hospital, Sydney, Australia; 7Royal Prince Alfred Hospital, Camperdown, NSW, Australia; 8University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic; 9Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South); 10National and Kapodistrian University, Athens, Greece; 11Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; 12GSK, Waltham, MA; 13GSK, Stevenage, United Kingdom; 14GSK, Collegeville, PA; 15GSK plc, Mississauga, ON, Canada; 16GSK, London, United Kingdom; 17GSK, Phoenixville, PA; 18GSK, Upper Providence, PA; 19Clinica São Germano, São Paulo, BrazilRelated Articles
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