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Pomalidomide plus Bortezomib/Dexamethasone Outcomes in Relapsed/Refractory Multiple Myeloma by Age, Prior Transplant, and High-Risk Cytogenetics

Conference Correspondent

The phase 3 OPTIMISMM trial was designed to compare the efficacy and safety of the combination of pomalidomide, bortezomib, and low-dose dexamethasone, collectively known as PVd, to the combination of bortezomib and low-dose dexamethasone (Vd) in participants with relapsed/refractory multiple myeloma (RRMM). OPTIMISMM data for patients at first relapse after 1 prior line of therapy showed that PVd had significantly longer median progression-free survival (PFS) versus treatment with Vd.

This subgroup analysis reports the efficacy and safety of PVd compared with Vd for groups separated by age, prior stem-cell transplant (SCT) status, and the presence of high-risk cytogenetic abnormalities that include del[17p], t[4;14], or t[14;16] in patients receiving this treatment after 1 prior line of therapy at first relapse.

In the OPTIMISMM trial, 226 of the 559 enrolled patients had 1 prior line of therapy and were included in this analysis. Two age subgroups were established, ≤65 years of age and >65 years of age. The group aged ≤65 years included 100 patients, 49 received PVd and 51 received Vd; the group aged >65 years included 126 patients, 62 received PVd therapy and 64 received Vd. In the ≤65 years group, 55.1% of those receiving PVd were lenalidomide refractory and 83.7% of those receiving PVd had prior bortezomib; 51.0% of those receiving Vd were lenalidomide refractory and 72.5% had prior bortezomib. In the >65 years group, 59.7% of those receiving PVd were lenalidomide refractory and 41.9% of those receiving PVd had prior bortezomib; 60.9% of those receiving Vd were lenalidomide refractory and 46.9% had prior bortezomib.

For both age-groups, PVd therapy resulted in significant improvement in PFS compared with Vd. Median PFS for those aged ≤65 years was 22.0 months with PVd versus 13.1 months with Vd (P = .0258). Median PFS for those aged >65 years was 17.6 months with PVd versus 9.9 months with Vd (P = .0369). PVd was also associated with a significantly higher overall response rate (ORR) for both age-groups; for those aged ≤65 years 89.8% versus 54.9% for PVd versus Vd, and for those aged >65 years 90.3% versus 54.4% for PVd versus Vd. For patients aged ≤65 years, the rate of very good partial response (VGPR) or better was 65.3% with PVd versus 17.6% with Vd; for patients aged >65 years, the rate was 58.0% with PVd versus 26.6% with Vd.

PVd resulted in significant improvements in PFS and ORR versus Vd in patients with or without prior SCT and in patients with high-risk cytogenetic abnormalities. Median PFS was 22.0 months for patients with prior SCT taking PVd (n = 56) versus 13.8 months for patients with prior SCT taking Vd (n = 54). For patients with no prior SCT, median PFS was 16.5 months for those taking VRd (n = 55) and 9.5 months for those taking Vd. ORR was 91.1% for patients with prior SCT taking PVd versus 57.4% for patients with prior SCT taking Vd. For patients with no prior SCT, ORR was 89.1% with VRd and 52.5% for Vd. Median PFS was 14.7 months for patients with high-risk cytogenetic abnormalities taking PVd (n = 18) versus 9.9 months for patients with high-risk cytogenetic abnormalities taking Vd (n = 14). ORR was 94.4% for patients with high-risk cytogenetic abnormalities taking PVd versus 57.1% for patients with high-risk cytogenetic abnormalities taking Vd.

For patients aged ≤65 years, the most common grade 3/4 treatment-emergent adverse events (TEAEs) with PVd versus Vd were neutropenia (49.0% vs 6.3%), infections (30.6% vs 14.6%), and thrombocytopenia (26.5% vs 18.8%). The same TEAEs were most common for patients aged >65 years with PVd versus Vd: neutropenia (25.8% vs 12.9%), infections (27.4% vs 16.1%), and thrombocytopenia (14.5% vs 22.6%).

In conclusion, for patients with lenalidomide-pretreated RRMM, PVd therapy resulted in improved PFS, ORR, and VGPR or better versus Vd regardless of patient age-group or prior SCT. The data for high-risk cytogenetic abnormalities are limited by the number of patients, but the results related achieved are promising. Safety signals for each subgroup were consistent with the known safety profiles for the therapies studied. This analysis supports the use of PVd after first relapse after lenalidomide treatment for patients regardless of age, prior SCT status, or high-risk cytogenetic abnormalities.


Reference

  • Abstract and Poster EP957. EHA 2020. June 12, 2020. OPTIMISMM subanalysis: pomalidomide, bortezomib, dexamethasone after 1 prior line of therapy in relapsed or refractory multiple myeloma by age, prior transplant, and high-risk cytogenetics.

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