An experimental, off-the-shelf immunotherapy that combines a targeted antibody and chemotherapy can lead to potentially durable responses in patients with multiple myeloma whose disease has relapsed or is resistant to other standard therapies, according to the DREAMM-2 trial published in Lancet Oncology.

The multi-center, international DREAMM-2 trial evaluated belantamab mafodotin and found that almost one-third of patients whose disease had returned after other therapies achieved a partial response or better when treated with this therapy.

Multiple myeloma is a cancer of the plasma cells, which build up in bone marrow and crowd out healthy blood cells. Patients enrolled in the trial were required to have the disease that had relapsed or was refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody.

The phase 2 trial involved 58 centers in 8 countries. Between June 2018 and January 2019, 196 patients were treated with either a low dose or high dose of the drug. In the low dose treatment group, 31% of patients achieved an overall response. Of that group, 60% had a very good partial response or better.  

In the high dose group, 34% achieved an overall response, with 59% of those patients achieving a very good partial response or better. Responses were achieved quickly, after a median of 1.4 months of treatment. The median progression-free survival was 2.9 months and 4.9 months, respectively, although it was not reached in patients who responded.

“These data build off the phase 1 trial that showed patient responses improved over time and contributed to prolonged progression free survival. Since this study did not reach the median duration of response, we anticipate that further follow-up on these patients will confirm these responses can be durable,” said Adam D. Cohen, MD, senior author and assistant professor of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania in a press release.

The most common adverse events (AEs) included nausea, fatigue, blurred vision, and dry eye. The majority of AEs were mild to moderate in severity. Microscopic changes to the lining of the cornea were noted through eye examination in 71% of low dose and 75% of high dose patients. Other AEs included thrombocytopenia, which was reported in 35% of low dose patients and 59% of high dose patients.

BCMA is a receptor on the surface of multiple myeloma cells that helps the cells grow and survive. Belantamab mafodotin is an experimental antibody-drug conjugate that consists of an antibody to target BCMA that is linked to a potent chemotherapy drug called MMAF.

After binding to BCMA, belantamab mafadotin is internalized into the melanoma cell and then releases the MMAF, leading to highly targeted killing of the myeloma within the bone marrow while limiting systemic chemotherapy adverse events. Belantamab mafadotin can also attract surrounding immune cells to attack the myeloma cells through a mechanism called antibody-dependent cellular cytotoxicity. 

Data from the DREAMM-2 study have been submitted to the FDA for consideration for approval.

Reference
BCMA-Targeted Immunotherapy Can Lead to Durable Responses in Multiple Myeloma [press release] Penn Medicine News website. Published December 17, 2019. https://www.pennmedicine.org/news/news-releases/2019/december/bcma-targeted-immunotherapy-can-lead-to-durable-responses-in-multiple-myeloma. Accessed January 13, 2020.