Multiple Myeloma

A single dose of ciltacabtagene autoleucel (cilta-cel), an investigational B-cell maturation antigen–directed CAR T-cell therapy, resulted in early, deep, and durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma, according to updated results from the phase 1b/2 CARTITUDE-1 clinical trial. These findings were reported by Saad Zafar Usmani, MD, FACP, Director, Plasma Cell Disorder Program, and Director, Clinical Research in Hematologic Malignancies, Levine Cancer Institute, Charlotte, NC, at the ASCO 2021 virtual annual meeting.

On July 9, 2021, the FDA accelerated the approval of a new indication for daratumumab and hyaluronidase-fihj (Darzalex Faspro; Janssen Biotech), in combination with pomalidomide (Pomalyst; Bristol Myers Squibb) and dexamethasone, for the treatment of adults with multiple myeloma who have received at least 1 previous line of therapy, including lenalidomide (Revlimid) or a proteasome inhibitor.

According to the American Cancer Society, nearly 35,000 new patients with multiple myeloma are diagnosed annually in the United States, with more than 12,000 deaths attributed to this cancer. However, with the introduction of several novel therapies, the outcomes for patients with newly diagnosed multiple myeloma have improved substantially over the past decade.

On February 26, 2021, the FDA accelerated the approval of melphalan flufenamide (Pepaxto; Oncopeptides AB), an alkylating drug, for the treatment, in combination with dexamethasone, of adults with relapsed or refractory multiple myeloma who have received ≥4 lines of therapy and whose disease is triple-refractory to ≥1 proteasome inhibitors, 1 immunomodulatory drug, and 1 CD-38–directed monoclonal antibody.

On December 18, 2020, the FDA approved selinexor (Xpovio; Karyopharm Therapeutics) in combination with bortezomib (Velcade) and dexamethasone for the treatment of adults with multiple myeloma after ≥1 previous therapies. The FDA granted this indication an orphan drug designation.

Bispecific antibodies are showing promise in patients with hematologic malignancies, notably relapsed or refractory multiple myeloma. Results from studies of 3 bispecific antibodies were presented at ASH 2020, showing deep and durable responses.

A post-hoc analysis of a pivotal clinical trial presented at ASH 2020 showed that the recently approved belantamab mafodotin-blmf (Blenrep), a first-in-class antibody targeting BCMA (B-cell maturation antigen), induced deep and durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma. This analysis of the ongoing, open-label DREAMM-2 study focused on 1-year outcomes based on the number of previous therapies. The results were presented by Sagar Lonial, MD, FACP, Chief Medical Officer, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA.

At the 2020 NCCN hematologic malignancies conference, multiple myeloma expert Shaji Kumar, MD, Consultant and Professor of Medicine, Division of Hematology, Mayo Clinic Cancer Center, Rochester, MN, discussed the “bonanza of treatment regimens for multiple myeloma.”

The combination of carfilzomib (Kyprolis) with lenalidomide (Revlimid) and dexamethasone (KRd) as induction therapy does not improve outcomes in patients newly diagnosed with multiple myeloma compared with the current standard of care with bortezomib (Velcade), lenalidomide, and dexamethasone (VRd).

Cellular therapy is becoming an attractive option for heavily pretreated patients with relapsed or refractory multiple myeloma.