Previous FDA Approval Withdrawn
Of note, belantamab mafodotin previously generated high interest for relapsed/refractory multiple melanoma, with early clinical results earning the therapy accelerated approval from the US Food and Drug Administration (FDA).
However, the FDA approval was subsequently revoked when the DREAMM-3 trial filed to achieve its primary outcome of superior PFS.
Dr. Trudel explained in an interview that since then, key changes have included combinations to improve responses, “overcome early progression and allow patients to benefit from the long duration of response that is achieved with belantamab mafodotin once they respond.”
While the ocular toxicities are common, Dr. Trudel underscored that they are “reversible and manageable.”
Antibody-Drug Conjugates: Less is More?
The ocular AEs observed with belantamab mafodotin are among the variety of unique side effects that are reported with the emerging antibody-drug conjugates, which, with precision targeting, deliver highly potent cytotoxic ‘payloads’ that bind to cells, earning the drugs nicknames such as “smart bombs” and “biologic missiles.”
In the case of belantamab mafodotin, the target is the protein B-cell maturation antigen (BCMA).
In a commentary on the DREAMM-8 study presented at the meeting, Sagar Lonial, MD, chair of the department of hematology and medical oncology at the Winship Cancer Institute of Emory University in Atlanta, noted the importance of BCMA: “In describing it to fellows, I explain that everything bad that a myeloma cell wants to do is mediated through BCMA.”
He underscored, however, the need to consider strategic dosing reductions, evoking iconic architect Ludwig Mies van der Rohe’s adage “less is more.”
“These results show belantamab mafodotin is clearly effective, but the question is how do we most effectively deliver it,” he said. “The idea that more is better is not necessarily the case when we’re talking about antibody drug conjugates,” he said.
“We need to use less [drug], less frequently, and do it in a way that preserves patient function,” Dr. Lonial said. “Missed doses may actually result in better safety profiles and maintain the efficacy of the treatment,” he said.
That being said, Dr. Lonial emphasized that the DREAMM-8 study is important, showing “the longest PFS in a pom-dex combination that we’ve seen in multiple myeloma.”
And “less ocular toxicity with similar efficacy are big wins,” he added.
“Future studies should take less frequent dosing into account as they are planned and as they’re executed.”
Other Therapies
In addition to the bortezomib, pom-dex regimen, other currently approved triplet regimens used at the first relapse in multiple myeloma include selinexor-bortezomib-dexamethasone, however that regimen is associated with adverse events that can pose challenges.
Furthermore, two chimeric antigen receptor (CAR) T-cell therapies — ciltacabtagene autoleucel and idecabtagene vicleucel, have emerged and been approved for multiple myeloma patients who have received at least one and at least two previous lines of therapy, respectively.
While those CAR T-cell therapies show important improvements in PFS benefit and quality of life compared with standard triplet regimens, access is a significant stumbling block, and safety issues, including the potential for cytokine release syndrome and neurotoxic effects are also a concern.
“Each regimen for myeloma comes with unique toxicities. Thus, it is beneficial for physicians and patients to have access to multiple treatment regimens to individualize to the patient, based on patient characteristics [and] drug related factors,” Dr. Trudel said.
The current DREAMM-8 regimen represents a convenient, “off-the-shelf option that can be given in the community,” she added.
The trial was sponsored by GSK. Dr. Trudel disclosed relationships with Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Jansen Biotech, Pfizer, Roche, and Sanofi. Dr. Lonial reported ties with Takeda, Amgen, Novartis, BMS, GSK, ABBVIE, Genentech, Pfizer, Regeneron, Janssen, and TG Therapeutics.