Talquetamab + pomalidomide for the treatment of RRMM: Preliminary safety and efficacy from MonumenTAL-2

Pomalidomide is an established immunomodulatory drug for the treatment of multiple myeloma (MM), which directly inhibits myeloma cell growth while enhancing immune activity.¹ As part of the MonumenTAL-2 trial,  talquetamab is under evaluation for efficacy and safety in the treatment of MM in combination with other agents, including pomalidomide.¹

Here, we summarize an oral abstract by Matous et al.¹ presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition on the safety and preliminary efficacy results from the talquetamab + pomalidomide arm of the MonumenTAL-2 trial.

Study design¹

• MonumenTAL-2 (NCT05050097) is an open-label, non-randomized phase Ib clinical trial evaluating the safety and efficacy of talquetamab combinations, including lenalidomide, daratumumab-lenalidomide, and pomalidomide.
• Patients with relapsed/refractory MM with two or more prior lines of therapy are eligible.
• Patients were treated with either:
  • 0.4 mg/kg subcutaneous talquetamab once weekly plus pomalidomide; or
  • 0.8 mg/kg subcutaneous talquetamab every two weeks plus pomalidomide.

Key findings¹

Safety¹

• Dose reductions due to toxicities were recorded in 34.3% of patients associated with talquetamab and 45.7% with pomalidomide.
• A death was recorded in one of the 11.4% of patients who discontinued treatment and was attributed to a pulmonary embolism.
• The rates of adverse events were comparable with the safety profiles of talquetamab and pomalidomide as individual agents (Table 1)
• Infections were common, occurring in 80% of patients at any grade.
  • Pneumonia and upper respiratory tract infections were the most frequent infections; however, rates of Grade 3/4 presentations were low (Table 1).

Efficacy¹

• Overall response rates were numerically higher in the 0.4 mg/kg cohort (Figure 1)
• Response was consistent across patient subgroups including those who were chimeric antigen receptor T cell exposed, pomalidomide exposed, have extramedullary disease, and those with high-risk disease.
• In the 0.4 mg/kg and 0.8 mg/kg cohorts, respectively:
  • 9-month progression-free survival rate was 93.8% and 75.5%.
  • 9-month duration of response rate was 100% and 83.9%.

Figure 1. Overall response rates in the talquetamab + pomalidomide arm of MonumenTAL-2* 

CR, complete response; ORR, overall response rate; Pom, pomalidomide; PR, partial response; QW, every week; Q2W, every two weeks; sCR, stringent complete response; Tal, talquetamab; VGPR, very good partial response.
*Adapted from Matous, et al.¹