Shebli Atrash, MD, member, Plasma Cell Disorders Program, Levine Cancer Institute, Atrium Health, discusses the development and current use of BCMA-targeted antibody-drug conjugates (ADCs) and CAR T-cell therapies for the treatment of patients with multiple myeloma.

BCMA is a relatively new actionable target for multiple myeloma, Atrash states. Belantamab mafodotin-blmf (Blenrep) was the first BCMA-directed therapy to be approved by the FDA in 2020 based on data from the phase 2 DREAMM-2 study (NCT03525678), which showed a promising overall response rate (ORR) in a relapsed/refractory population.

The emergence of BCMA-directed CAR T-cell therapy has also had a profound effect on the multiple myeloma treatment landscape, Atrash continues. In 2021, idecabtagene vicleucel (Abecma) became the first cell-based gene therapy to gain FDA approval for multiple myeloma based on a high ORR. A second CAR T-cell therapy, ciltacabtagene autoleucel (Carvykti) also displayed a high ORR in the phase 1b/2 CARTITUDE-1 trial (NCT03548207), cementing it as a highly effective treatment option in the relapsed/refractory setting.

Despite these clinical advances, it is important to evaluate the different safety and toxicity profiles of each drug class, Atrash cautions. The main limitation of belantamab mafodotin is its high rate of corneal toxicity, whereas both CAR T products have a greater incidence of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome. Evaluation and management of these adverse effects are integral to mitigating risk, Atrash concludes.

Videos

Shebli Atrash, MD, discusses the development and current use of BCMA-targeted antibody-drug conjugates and CAR T-cell therapies for the treatment of patients with multiple myeloma.

Dr. Atrash on the Evolution of BCMA-Directed Therapies in Multiple Myeloma

Shebli Atrash, MD, a physician in hematology and medical oncology at Levine Cancer Institute, Atrium Health, discusses investigational combinations with venetoclax (Venclexta) in relapsed/refractory multiple myeloma.

At the 2019 ASH Annual Meeting, Jonathan L. Kaufman, MD, from Emory University School of Medicine, presented data on the combination of venetoclax and dexamethasone. Dexamethasone encourages plasma cells to be more dependent on BCL-2, and venetoclax inhibits BCL-2, so the drugs are thought to act synergistically, explains Atrash. Although the early-phase trial enrolled a small number of patients, the overall response rates (ORRs) were in the range of 87%, says Atrash.

Additionally, the combination of daratumumab (Darzalex), venetoclax, and dexamethasone was also evaluated in an early-phase trial. Notably, 4 patients enrolled on the trial had 11;14 translocations. Another arm of the trial evaluated venetoclax in combination with daratumumab, bortezomib (Velcade), and dexamethasone in patients who had received 1 to 3 prior lines of treatment. In order to be eligible for enrollment, patients could not be refractory to a proteasome inhibitor, says Atrash. The regimen was found to be well tolerated, and the ORRs were in the range of 95% in both arms, concludes Atrash.

Shebli Atrash, MD, discusses investigational combinations with venetoclax (Venclexta) in relapsed/refractory multiple myeloma.

Dr. Atrash on Investigational Combinations With Venetoclax in Relapsed/Refractory Multiple Myeloma

Shebli Atrash, MD, a physician in hematology and medical oncology at Levine Cancer Institute, Atrium Health, discusses the results of the BELLINI trial examining patients with relapsed/refractory multiple myeloma.

The phase III BELLINI trial compared venetoclax (Venclexta) versus placebo combined with bortezomib (Velcade) and dexamethasone in patients with relapsed/refractory multiple myeloma, explains Atrash. The trial met its primary endpoint of progression-free survival and showed venetoclax is superior to placebo; however, the risk of death increased in the venetoclax arm, says Atrash.

Patients were enrolled in the BELLINI trial regardless of translocation status or BCL-2 status, but results showed that patients with t(11;14) or high BCL-2 expression derived the most benefit from venetoclax. Going forward, Atrash recommends trials using venetoclax to target this patient population with multiple myeloma.

Shebli Atrash, MD, discusses the results of the BELLINI trial examining patients with relapsed/refractory multiple myeloma.

Shebli Atrash, MD

Articles

Dr. Atrash on the Evolution of BCMA-Directed Therapies in Multiple Myeloma

Dr. Atrash on Investigational Combinations With Venetoclax in Relapsed/Refractory Multiple Myeloma

Dr. Atrash on the BELLINI Trial Results in Relapsed/Refractory Multiple Myeloma