Blenrep together with Velcade and dexamethasone improved survival and response charges in comparison with Darzalex in sufferers with relapsed or refractory a number of myeloma.
Sufferers with relapsed/refractory a number of myeloma skilled important enhancements in general survival (OS) when handled with Blenrep (belantamab mafodotin) together with Velcade (bortezomib) and dexamethasone (BVd) versus these handled with Darzalex (daratumumab) plus Velcade and dexamethasone (DVd), trial outcomes have proven.
Up to date knowledge from the part 3 DREAMM-7 trial was offered throughout the 2024 ASH Annual Assembly and Exposition.
At a median follow-up of 39.4 months, the median OS was not reached (NR) in each the BVd (243 sufferers) and DVd (251 sufferers) arms. The expected median OS based mostly on modeling is 84 months with BVd versus 51 months with DVd. The estimated 24-month survival charges within the respective arms had been 79% and 67%; these respective charges at 36 months are 74% and 60%.
Furthermore, deeper responses had been achieved and maintained with Blenrep vs Darzalex. The target response charge (ORR) with BVd was 83.1% versus 71.3% with DVd. The median period of response (DOR) with BVd was greater than double that achieved with DVd, at 40.8 months and 17.8 months, respectively.
The proportion of those that achieved an entire response or higher and minimal residual illness (MRD) negativity with a sensitivity of 10-5 was 25.1% within the BVd arm versus 10.4% within the DVd arm. The proportion of sufferers who skilled an excellent partial response or higher and MRD negativity with a sensitivity of 10-5 within the respective arms was 38.7% and 17.9%, respectively.
Glossary:
General survival (OS): the time a affected person lives, no matter illness standing.
Goal response charge (ORR): sufferers who reply partially or fully to therapy.
Period of response (DOR): the size of time a affected person responds to therapy.
Full response (CR): the disappearance of most cancers.
Minimal residual illness (MRD): small quantities of remaining most cancers cells.
Development-free survival (PFS): the time a affected person lives with out their illness spreading or worsening.
Therapy profit derived with BVd was additionally maintained after subsequent antimyeloma remedy. The median time to second goal illness development (PFS2) with BVd was NR versus 33.4 months with DVd.
“BVd demonstrated an early, sustained and statistically important OS profit in a head-to-head trial in opposition to the [Darzalex] mixture,” Dr. Vania Hungria of Clinica Sao Germano, in Sao Paulo, Brazil, stated in a presentation of the info. “DREAMM-7 has now proven statistically important [progression-free survival (PFS)], OS, DOR and MRD negativity advantages in contrast with DVd. [As such,] these outcomes additional assist using BVd as a possible new normal of care in relapsed or refractory a number of myeloma.”
The randomized, open-label, part 3 DREAMM-7 research enrolled sufferers with a number of myeloma who had been not less than 18 years of age and acquired not less than one prior line of remedy and skilled documented progressive illness (PD) after their most up-to-date line. Sufferers couldn’t have earlier publicity to anti-BCMA remedy, nor might they’ve illness that was refractory to or illiberal of Darzalex or Velcade.
Individuals had been randomly evenly assigned to obtain Blenrep at a dose of two.5 milligrams per kilogram (mg/kg) intravenously (IV) each three weeks paired with Velcade and dexamethasone versus Darzalex at a dose of 16 mg/kg IV weekly for cycles 1 to three after which each three weeks for cycles 4 to eight. For cycles 9 and later, these within the investigative and management arms acquired single-agent Blenrep at 2.5 mg/kg IV each three weeks or Darzalex monotherapy at 16 mg/kg IV each 4 weeks, respectively. Therapy continued till the research concluded, consent was withdrawn, PD, demise or insupportable toxicity.
PFS served because the trial’s major finish level, and at a median follow-up of 28.2 months this was met. The median PFS of 36.6 months with BVd versus 13.4 months with DVd translated to a 59% discount within the danger of illness development or demise. On the time of the first evaluation, median OS was NR in each arms, however a powerful development favored the BVd routine. In November 2024, the FDA accepted a biologics license utility looking for the approval of BVd in sufferers with a number of myeloma who’ve acquired not less than 1 prior remedy based mostly on DREAMM-7 knowledge. The goal motion date is July 23, 2025.
Key secondary finish factors of the trial included OS, DOR and MRD. Finish factors had been examined within the following hierarchy: PFS, adopted by OS and DOR, adopted by MRD. Extra secondary finish factors of curiosity included CR charge, ORR, medical profit charge, time to response, time to development, PFS2 and antagonistic results (unwanted effects), notably ocular findings.
Of the entire 494 sufferers enrolled, 243 had been assigned to the BVd arm and 251 had been assigned to the DVd arm; 242 and 246 sufferers, respectively, acquired therapy. The next share of sufferers on the BVd arm remained on remedy versus these on the DVd arm, at 25% and 15%, respectively. The most typical purpose for discontinuation within the BVd arm was PD (30%), adopted by toxicity (21%), doctor determination (13%), affected person withdrawal (10%), loss to follow-up (lower than 1%) and protocol-defined stopping standards reached (lower than 1%).
The info cutoff date of the evaluation shared throughout the assembly was Oct. 7, 2024. Right now level, the median period of publicity to BVd was 15.9 months versus 12.8 months within the DVd arm. Baseline traits and prior remedies acquired proved to be balanced throughout the arms, based on Hungria, who added that roughly half of sufferers acquired one prior line of remedy.
“Extra sufferers within the BVd group discontinued therapy early because of development and went on to obtain a subsequent antimyeloma remedy,” Hungria stated. “The most typical subsequent remedy in each arms embrace immunomodulatory medicine like [Revlimid (lenalidomide)] and [Pomalyst (pomalidomide)]. Of sufferers who acquired subsequent therapies, greater than half acquired anti-CD38 monoclonal antibodies instantly after BVd, and [Kyprolis (carfilzomib)] was given usually after DVd.”
Concerning security, any-grade unwanted effects (AEs) occurred in all sufferers within the BVd and DVd arms; these results had been associated to review therapy for 100% and 95% of sufferers, respectively. Grade 3 (extreme) or 4 (life-threatening) AEs occurred in 95% and 78% of sufferers, respectively, with 92% and 67% associated to review therapy. Within the BVd arm, AEs led to dose delays or reductions for 95% and 75% of sufferers, respectively; within the DVd arm, these charges had been 76% and 59%. AEs resulted in everlasting discontinuation of therapy for 32% of these given BVd and 19% of those that acquired DVd. Critical AEs associated to any research therapy had been skilled by 21% and 13% of sufferers and critical AEs proved to be deadly for 11% and eight% of sufferers.
“AEs had been according to the identified security profile for the person brokers in every routine,” Hungria famous. “Though the BVd arm had numerically greater general charges of grade 3 or 4 and critical AEs, when adjusting for whole therapy publicity, security outcomes had been typically comparable between arms. There have been extra deaths because of myeloma within the DVd vs the BVd arm.”
She added that thrombocytopenia was extra frequent within the BVd arm, even when adjusted for publicity. General, an infection charges had been comparable between the arms and according to the first evaluation. Within the BVd and DVd arms, exposure-adjusted charges of infections per 100 person-years had been 43.75% and 48.71% for all-grade occasions, and 19.89% versus 14.29%, respectively, for grade 3 or greater occasions.
“About two-thirds of sufferers didn’t have a clinically significant drop in best-corrected visible acuity, [BCVA]” Hungria stated. “General, the ocular security profile is according to the first evaluation. Practically all sufferers with worsening of imaginative and prescient to twenty/50 had decision to regular baseline or enchancment of the primary occasion. The two% of sufferers with an ongoing occasion had insubstantial follow-up to evaluate for decision.” Within the BVd arm, blurred imaginative and prescient was probably the most frequent ocular occasion skilled; 68% skilled an any-grade occasion and 24% skilled a grade 3 or 4 occasion. Ten p.c of sufferers discontinued because of an ocular occasion.
“The interval between doses elevated with time because of dose modification, from preliminary three weeks as much as 12 weeks,” Hungria famous. “Regardless of the prolonged dose intervals, the responses had been maintained.” Twenty-three p.c of sufferers skilled 20/50 or worse ocular occasions within the first three months and prevalence typically dropped thereafter. Notably, the speed of therapy discontinuation because of these occasions was low, she concluded.
Reference:
Belantamab mafodotin, bortezomib, and dexamethasone vs daratumumab, bortezomib, and dexamethasone in relapsed/refractory a number of myeloma: general survival evaluation and up to date efficacy outcomes of the part 3 DREAMM-7 trial” by Dr. Vania Hungria et al., Blood.
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