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.
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.
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).
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).
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.
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.
CAR-T for myeloma, impressive response rate, overall survival not reached.
The Bi-specific antibody era has started full-force with impressive results and reasonable toxicities, in different hematological neoplasms. Community oncology adoption of Bi-specific antibody will be successful, once standard operating procedures are in place, and multidisciplinary training takes place insofar as management of CRS. I am optimistic as to the uptake of this class of drugs in 1-2 years, pending payer coverage issues.
MRD status in MM has unquestionable prognostic informational value, however many questions remain as how to address positive / negative MRD results. Should we de-escalate or stop Rx? When? Can we escalate Rx if + MRD? Which regimen, how long? It will be another few years till objective data are available. I do see value in at least having identification of clonality established upfront for tracking.
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