Is There a Possibility of a Cure in Multiple Myeloma?

Traditionally thought of as a disease that cannot be cured, researchers of a new paper in Advances in Oncology are posing the possibility of a cure in multiple myeloma (MM).

MM has historically been considered a chronic disease, even as newer treatments have greatly improved rates of survival for the disease. Despite improved survival, many patients who are able to achieve complete responses (CRs) to treatment often eventually experience disease progression.

“Multiple myeloma is a particularly challenging malignancy in which to define cure because of its often indolent nature that leads to an alternating pattern of disease response and progression,” explained the researchers. “It is for this reason that the International Myeloma Working Group (IMWG) response criteria specifically use ‘response’ and do not use the word ‘remission’ as is used in other malignancies.’

However, according to the group, there is a possibility for MM to be considered a curable disease, which they outlined as being defined by: no evidence of disease, no longer on treatment, limited or no comorbidities, and mortality that is similar to age-match controls.

The group highlighted the utility of minimal residual disease (MRD), which has gained credibility as a prognostic tool, for determining absence of disease and predicting long-term outcomes. A growing amount of research has shown MRD to be a more reliable prognostic indicator than more traditional markers, such as CR or sustained CR.

Specifically, the researchers underscored the use of sustain MRD negativity, defined as 2 consecutive negative MRD results done at least 1 year apart. The group cited several studies, including the phase 2 FORTE study of patients with MM, in which sustained MRD-negativity was associated with superior progression-free survival.

“If sustained MRD-negativity becomes one of the key checkpoints to a functional cure, then the eradication of MRD becomes essential for patients with MM who have not experienced clinical progression,” wrote the group. “This, of course, has important implications to patients, clinicians, and whomever else is bearing the cost of interventions to eradicate MRD. A combined risk and MRD-adapted strategy may prove to be an intriguing treatment approach to intensity treatment for those who might most benefit, using immunotherapeutic modalities such as monoclonal antibodies, bispecific T-cell redirectors, and/or chimeric antigen receptor T-cell therapy.”

Honing in on indicators for which patients may considered cured, the researchers highlighted patients who are considered exceptional responders—those without disease progression or death at least 8 years after starting treatment—the researchers argue that newer treatments may results in as many as 30% to 40% of patients being exceptional responders.

For example, in the phase 3 GIMEMA-MMY-3006 study of bortezomib, thalidomide, a d dexamethasone (VTd) versus Td followed by tandem ASCT, 2 cycles of consolidation, and maintenance therapy with dexamethasone, VTd yielded a 10-year PFS rate of 34%.

Reference

Derman B, Jakubowiak A. Moving toward a cure in multiple myeloma: Eradication of measurable residual disease. Adv in Oncol. 2022;2(1);159-169. doi:10.1016/j.yao.2022.02.012