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Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma
Meletios Athanasios Dimopoulos1, Meral Beksac1, Ludek Pour1
1From the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens (M.A.D.), and General Hospital Evangelismos (S.D.) - both in Athens; the Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey (M.B.); the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the First Faculty of Medicine, Charles University, and General Hospital, Prague (I.S.), and the Fourth Department of Internal Medicine-Hematology, University Hospital Hradec Králové, and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (J.R.) - all in the Czech Republic; Leningrad Regional Clinical Hospital, Saint Petersburg, Russia (V.V.); the University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); Medical University of Lodz, Łódź, Poland (P.R.); Sungkyunkwan University and Samsung Medical Center, Seoul, South Korea (K.K.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (M.C.); the Division of Clinical Oncology-Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo (K.S.); GSK, Durham, NC (K.M.); GSK, Philadelphia (F.P.), and GSK, Collegeville (N.S., B.E.K., J.O.) - both in Pennsylvania; GSK, Stevenage, United Kingdom (A.P.-J.); GSK, Waltham, MA (X.L.Z., G.F.); the Hematology Department, Cancer Research Center-Instituto de Investigación Biomédica de Salamanca, University Hospital of Salamanca, Salamanca, Spain (M.-V.M.); and the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto (S.T.).
Background:
Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse.
Methods:
In this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy. The primary end point was progression-free survival. Disease response and safety were also assessed.
Results:
A total of 302 patients underwent randomization; 155 were assigned to the BPd group, and 147 to the PVd group. At a median follow-up of 21.8 months (range, <0.1 to 39.2), the 12-month estimated progression-free survival with BPd was 71% (95% confidence interval [CI], 63 to 78), as compared with 51% (95% CI, 42 to 60) with PVd (hazard ratio for disease progression or death, 0.52; 95% CI, 0.37 to 0.73; P<0.001). Data on overall survival were immature. The percentage of patients with a response to treatment (partial response or better) was 77% (95% CI, 70 to 84) in the BPd group and 72% (95% CI, 64 to 79) in the PVd group; 40% (95% CI, 32 to 48) and 16% (95% CI, 11 to 23), respectively, had a complete response or better. Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group. Ocular events occurred in 89% of the patients who received BPd (grade 3 or 4 in 43%) and 30% of those who received PVd (grade 3 or 4 in 2%); ocular events in the BPd group were managed with belantamab mafodotin dose modification. Ocular events led to treatment discontinuation in 9% of the patients in the BPd group and in no patients in the PVd group.
Conclusions:
Among lenalidomide-exposed patients with relapsed or refractory myeloma, BPd conferred a significantly greater benefit than PVd with respect to progression-free survival, as well as deeper, more durable responses. Ocular events were common but were controllable by belantamab mafodotin dose modification. (Funded by GSK; DREAMM-8 ClinicalTrials.gov number, NCT04484623; EudraCT number, 2018-004354-21.).
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