Pomalidomide Added to the Regimen in First Relapse Extends PFS in Multiple Myeloma

Web Exclusives - Multiple Myeloma

Chicago, IL—The triplet regimen of pomalidomide (Pomalyst), bortezomib (Velcade), and low-dose dexamethasone (PVd) significantly extended progression-free survival (PFS) compared with the doublet of bortezomib plus dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma who had previously received lenalidomide (Revlimid) therapy, according to new data presented at ASCO 2018.

The results of the phase 3 OPTIMISMM clinical trial showed a 39% risk reduction in disease progression or death with PVd compared with Vd, said Paul G. Richardson, MD, Clinical Program Leader, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston.

These results "support the use of PVd in first relapse in patients with relapsed or refractory multiple myeloma and prior exposure to lenalidomide," Dr Richardson said. Pomalidomide is approved by the FDA for the treatment of relapsed or refractory multiple myeloma after ≥2 therapies, including lenalidomide, an immunomodulator. Furthermore, in patients with lenalidomide-refractory disease, the use of pomalidomide treatment has demonstrated an overall survival (OS) advantage.

Triplet combinations of pomalidomide, bortezomib, and dexamethasone have demonstrated encouraging ac­tivity in patients with lenalidomide-refractory disease.

"With the recent approval of lenalidomide as maintenance by the FDA, it's become very important to understand what benefits most patients for whom lenalidomide is no longer a treatment option and are progressing on lenalidomide therapy," said Dr Richardson.

The OPTIMISMM Study

The OPTIMISMM clinical trial included 559 patients who had received 1 to 3 previous lines of therapy and ≥2 cycles of lenalidomide therapy. All patients were randomized to the PVd or Vd regimen.

In 21-day cycles, patients in the triplet arm received pomalidomide 4 mg daily on days 1 to 14; bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of cycles 1 to 8, and on days 1 and 8 of cycles 9 and higher; and dexamethasone 20 mg daily (10 mg for those aged >75 years) on the days of, and after, receiving bortezomib.

The baseline characteristics were generally well-balanced between the 2 arms (median age, approximately 68 years). Approximately 20% of patients in each arm had high-risk cytogenetics (del17p, t[4;14], and/or t[14;16]).

Approximately 70% of patients had lenalidomide-refractory disease, and 9% of patients who received PVd and 12% of those who received Vd had disease progression with bortezomib maintenance therapy. Approximately 70% of patients had disease refractory to their last previous regimen.

The median treatment duration was almost twice longer with PVd than with Vd (8.8 months vs 4.9 months, respectively). The most common reason for treatment discontinuation was progressive disease, which was 39.1% in the PVd arm and 47.1% in the Vd arm.

With a median follow-up of 16 months, the median PFS was 11.2 months in the PVd arm and 7.1 months in the Vd arm (hazard ratio [HR], 0.61; P <.0001). The PFS advantage with PVd was observed across patient subgroups and regardless of lenalidomide-refractory status, and was maintained through the next line of therapy.

In patients who received only 1 previous line of therapy, the advantage with adding pomalidomide to the treatment regimen was even greater: a median PFS of 20.7 months versus 11.63 months with Vd (HR, 0.54; P = .0027).

In the lenalidomide-refractory subgroup, the median PFS was 9.53 months in the PVd arm versus 5.59 months in the Vd arm (HR, 0.65; P <.001). In patients who were exposed to lenali­d­omide but did not have disease re­fractory to lenalidomide, "the difference was more striking," said Dr Richardson—with a median PFS of 22.0 months with PVd and 11.6 months with Vd (HR, 0.48; P = .001). The OS data were not mature at the time of the presentation.

The overall response rate (ORR) was significantly higher with PVd (82.2%) versus Vd (50%). In patients with only 1 previous line of therapy, the ORR was 90.1% with PVd versus 54.8% with Vd.

"PVd led to deeper responses, with higher stringent complete response or complete response, and more very good partial responses than Vd," Dr Richardson said.

Furthermore, the time to next therapy was extended significantly with the addition of pomalidomide, from 8.5 months to 22.2 months (HR, 0.42; P <.001).

The safety profile with PVd was consistent with known toxicities associated with pomalidomide and low-dose dexamethasone. The most common grade 3 or 4 treatment-emergent adverse events that occurred more often with PVd than Vd were neutropenia (42% vs 9%, respectively) and infections (31% vs 18%, respectively).

Related Items
Multiple Myeloma Year in Review Introduction
2020 Year in Review - Multiple Myeloma published on February 1, 2021 in Multiple Myeloma
MRD Status Comparison by 3 Techniques in Patients with Newly Diagnosed Transplant-Eligible MM
2020 Year in Review - Multiple Myeloma published on February 1, 2021 in Multiple Myeloma
Definition and Prediction of Unsustained Complete Remission in Patients with Transplant-Eligible MM
2020 Year in Review - Multiple Myeloma published on February 1, 2021 in Multiple Myeloma
Assessment of Options for Patients with RRMM with Triple-Class Exposure: Literature Review Indicates Urgent Need for New Treatments
2020 Year in Review - Multiple Myeloma published on February 1, 2021 in Multiple Myeloma
GEM-POMCIDEX Study: Treatment of Patients with RRMM Using Pomalidomide, Cyclophosphamide, and Dexamethasone (POMCIDEX)
2020 Year in Review - Multiple Myeloma published on February 1, 2021 in Multiple Myeloma
In Newly Diagnosed, Transplant-Eligible Patients with MM, Consolidation Treatment with VRD Followed by Lenalidomide Maintenance versus Maintenance Alone
2020 Year in Review - Multiple Myeloma published on February 1, 2021 in Multiple Myeloma
FORTE Trial: Analysis of Survival in Patients with Newly Diagnosed Transplant-Eligible MM
2020 Year in Review - Multiple Myeloma published on February 1, 2021 in Multiple Myeloma
TOURMALINE-MM4 Study: Patients with NDMM Not Treated with Stem-Cell Transplantation and Maintenance Therapy with Ixazomib
2020 Year in Review - Multiple Myeloma published on February 1, 2021 in Multiple Myeloma
Patients with Newly Diagnosed Transplant-Eligible MM and Minimal Residual Disease after Treatment with Ixazomib, Lenalidomide, and Dexamethasone
2020 Year in Review - Multiple Myeloma published on February 1, 2021 in Multiple Myeloma
HORIZON: Use of Melflufen plus Dexamethasone in Patients with RRMM Refractory to Pomalidomide and/or an Anti-CD38 Monoclonal Antibody
2020 Year in Review - Multiple Myeloma published on February 1, 2021 in Multiple Myeloma
Last modified: April 27, 2020