OPTIMISMM trial: A subanalysis by frailty and bortezomib dose adjustment

Dose adjustments are commonplace in the treatment of multiple myeloma (MM), particularly in the older and frail population who are less able to tolerate toxicities. Clinical trial data from the OPTIMISMM trial (NCT01734928) provided evidence for the use of pomalidomide, bortezomib, and dexamethasone (PVd) in the treatment of relapsed/refractory MM. However, there is a lack of understanding of the outcomes of this combination in patients who are frail or require a dose adjustment.¹

Here, we summarize a subanalysis by Oriol et al. published in Clinical Lymphoma, Myeloma and Leukemia on results from the OPTIMISMM trial by frailty status and bortezomib dose adjustment.

The Multiple Myeloma Hub has previously covered the overall results from OPTIMISMM here.

Study design¹

• Patients included in OPTIMISMM were categorized into frail and non-frail populations by age, Charlson Comorbidity Index, and Eastern Cooperative Oncology Group performance status.
• Data were also collected on bortezomib dose adjustments, interruptions, and treatment cessation.
• Patient outcomes in these subcohorts were compared with the overall trial data.

Key findings¹

• A total of 559 patients were included in this analysis.
  • 33.1% of patients in the PVd cohort and 33.5% of those in the bortezomib and dexamethasone (Vd) cohort were classified as frail.
• In the PVd cohorts, a higher overall response rate (ORR) and median progression-free survival (PFS) were observed in the non-frail arm
  • ORR; non-frail 82.8% vs frail 79.6%
  • Median PFS; non-frail 14.7 months vs frail 9.7 months
  • Patients treated with PVd experienced significantly higher ORR and PFS than the Vd cohort, regardless of frailty status
• Treatment discontinuation for PVd was more common in frail patients at 30.1% vs 19.2% among non-frail patients
  • However, median duration of treatment (DoT) was comparable between arms
• Longer median DoT and PFS were observed in patients who received a PVd dose adjustment than those without
  • Median DoT; with adjustment 9.3 months vs without 4.5 months
  • Median PFS; with adjustment 12.1 months vs without 8.4 months
• Overall, response rates improved in patients treated with PVd and in those receiving dose adjustments, regardless of frailty status (Figure 1).

CI, confidence interval; CR, complete response; NE, not evaluable; OR, odds ratio; ORR, overall response date; PD, progressive disease; PR, partial response; sCR, stringent CR; SD, stable disease; VGPR, very good PR.
*Data from Oriol, et al.¹

Key learnings1

Dose adjustments in patients treated with PVd resulted in improved efficacy outcomes compared with those without. Frail patients experienced poorer overall outcomes, compared with non-frail patients treated with the same regimen. Treatment with PVd consistently resulted in improved outcomes compared with Vd, regardless of frailty status. PVd is a viable option for further research for the treatment of patients with relapsed/refractory MM, including older and frail patients.