DREAMM-7 update: Subgroup analyses from a phase 3 trial of belantamab mafodotin (belamaf) + bortezomib and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in relapsed/refractory multiple myeloma (RRMM)

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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.

DREAMM-7 Update: Subgroup Analyses From a Phase 3 Trial of Belantamab Mafodotin (Belamaf) + Bortezomib and Dexamethasone (BVd) vs Daratumumab, Bortezomib, and Dexamethasone (DVd) in Relapsed/Refractory Multiple Myeloma (RRMM)

María-Victoria Mateos, MD, PhD, an associate professor of medicine and director of the Myeloma unit at the University of Salamanca in Spain, discusses the significance of the ongoing phase 3 CANOVA trial,which is examining venetoclax (Venclexta) in patients with relapsed/refractory t(11;14) multiple myeloma.

In the multicenter, open-label CANOVA study, patients with relapsed/refractory, t(11;14)–positive multiple myeloma were randomized to receive either venetoclax plus dexamethasone or pomalidomide (Pomalyst) plus dexamethasone. t(11;14) in multiple myeloma is a cytogenetic abnormality, usually present in approximately 15% to 20% of patients, says Mateos. 

Venetoclax is the first targeted therapy being used to treat patients with multiple myeloma, explains Mateos. This is important because if all patients with t(11;14) in this study are shown to be candidates to receive venetoclax, then all patients with the translocation can receive this drug, concludes Mateos.

María-Victoria Mateos, MD, PhD, discusses the significance of the ongoing phase 3 CANOVA trial, which is examining venetoclax in patients with relapsed/refractory t(11;14) multiple myeloma.

Dr. Mateos on the Significance of the CANOVA Trial in R/R t(11;14) Myeloma

María-Victoria Mateos, MD, PhD, associate professor of medicine, and director of the Myeloma unit at the University of Salamanca in Spain, discusses the design of the ongoing phase 3 CANOVA trial in patients with relapsed/refractory t(11;14) multiple myeloma.

The ongoing multicenter, open-label study will randomize patients with relapsed/refractory t(11;14) multiple myeloma to venetoclax (Venclexta) plus dexamethasone or pomalidomide (Pomalidomide) plus dexamethasone (Pd). The primary end point of the study is progression-free survival, says Mateos. Key secondary end points include the rate of very good partial response or better, overall response rate, overall survival, duration of response, rate of minimal residual disease, pharmacokinetics of venetoclax, and safety.

The rationale for the trial stems from the fact that venetoclax is a highly selective and potent oral BCL-2 inhibitor that has shown promising activity alone or in combination with other agents in patients with t(11;14), and Pd is a standard option for patients who have been previously exposed to proteasome inhibitors and immunomodulatory drugs. The estimated enrollment is 244 patients, says Mateos. To be eligible for enrollment, patients had to have received at least 1 proteasome inhibitor and have disease that is refractory to lenalidomide (Revlimid).

María-Victoria Mateos, MD, PhD, discusses the design of the ongoing phase 3 CANOVA trial in patients with relapsed/refractory t(11;14) multiple myeloma.

Dr. Mateos on the Ongoing CANOVA Trial in t(11;14) Multiple Myeloma

María-Victoria Mateos, MD, PhD, associate professor of medicine, and director of the Myeloma unit at the University of Salamanca in Spain, discusses the rationale for the posthoc analysis of the phase III ARROW study in multiple myeloma. 

In October 2018, findings from the ARROW trial led to the FDA approval of a once-weekly 70 mg/m

 dose of carfilzomib (Kyprolis) in combination with dexamethasone in patients with relapsed/refractory disease. A progression-free survival (PFS) benefit was reported with the once weekly dose versus a twice weekly dose of 27 mg/m

A posthoc analysis demonstrated that the PFS benefit was reported across subgroups, including patients over the age of 65, explains Mateos. 

As such, Mateos states that older age should not prohibit patients from receiving the higher dose of carfilzomib. Though, frailty should be assessed to see which regimen would be best tolerated. 

María-Victoria Mateos, MD, PhD, discusses the rationale for the posthoc analysis of the phase III ARROW study in multiple myeloma. 
 

Dr. Mateos on Posthoc Analysis of ARROW Study in Multiple Myeloma

Maria-Victoria Mateos, MD, PhD, associate professor of medicine, and director of the Myeloma unit at the University Hospital of Salamanca in Spain, discusses the impact of performance status on the outcomes of patients with multiple myeloma in the phase III ARROW trial.

In the ARROW trial, investigators showed that carfilzomib (Kyprolis) dosed once weekly at 70 mg/m

 with dexamethasone induced a prolonged progression-free survival (PFS) versus the standard twice-weekly dose of 27 mg/m

 in patients with relapsed/refractory multiple myeloma. These findings served as the basis for the FDA approval of the once-weekly regimen in October 2018.

When investigators applied a frailty score to the overall patient population, they identified 3 distinct patient populations: fit, intermediate, and frail. Each group represented approximately one-third of the total patient population and were well balanced between dosing schedules, says Mateos. The PFS benefit with the higher dose of carfilzomib was maintained irrespective of frailty status, demonstrating the feasibility of the higher dose across all patient subgroups. However, Mateos notes that fit patients derived the most benefit from the higher dose of carfilzomib with a hazard ratio of 0.53.

Dr. Mateos on Frail Patients With Multiple Myeloma in the ARROW Trial

Maria-Victoria Mateos, MD, PhD, consultant physician, hematology department, Hospital Universitario de Salamanca, discusses ixazomib-lenalidomide-dexamethasone in multiple myeloma.

The trial demonstrated that the oral regiman ixazomib-lenalidomide-dexamethasone (IRd) improved progression-free survival (PFS) compared to placebo plus lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM).  

In the past, lenalidomide-dexamethasone was the standard of care, but now there are numerous options for three-drug combinations for patients that have relapsed after one to three prior lines of therapy, says Mateos.

There may be challenges selecting the right three-drug combination, as results are similar between them. The main advantage of IRd is that it is an all oral combination, requiring less hospital visits, says Mateos.

Dr. Mateos on Ixazomib-Lenalidomide-Dexamethasone in Multiple Myeloma

Maria-Victoria Mateos, consultant physician, hematology department, Hospital Universitario de Salamanca, MD, PhD, discusses the TOURMALINE-MM1 trial in multiple myeloma.

The phase III trial investigated the impact of prior therapy on efficacy and safety of oral ixazomib-lenalidomide-dexamethasone (IRd) compared to placebo plus lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM).

The IRd combination resulted in a significant improvement in progression free survival (PFS) compated to the control arm, says Mateos.

The benefit was sustained across different groups of patients regardless of prior lines of therapy.

Dr. Mateos on Ixazomib-Lenalidomide-Dexamethasone in Relapsed/Refractory Multiple Myeloma

MarÃ&shy;a-Victoria Mateos, MD, PhD, associate professor, hematology, University Hospital of Salamanca, Salamanca, Spain, discusses the design and results of a phase II trial that she presented at the 2013 American Society of Hematology (ASH) Meeting.

In the GEM2010MAS65 trial, researchers conducted a comparison of sequential and alternating administration of bortezomib, melphalan, and prednisone and lenalidomide plus dexamethasone in elderly patients with newly diagnosed multiple myeloma.

The combination of melphalan, bortezomib, lenalidomide, and steroids in this patient population in a sequential or alternating scheme is feasible, Mateos says. In terms of complete remission, the alternating scheme showed superior efficacy, though a longer follow-up is needed.

Maria-Victoria Mateos, MD, PhD

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