Pomalidomide, dexamethasone, and daratumumab in relapsed refractory multiple myeloma after lenalidomide treatment

Abstract

Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1–21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. Per protocol, all patients (N = 112) had received lenalidomide in their most recent prior regimen (75.0% lenalidomide refractory). ORR was 77.7% (76.2% in lenalidomide-refractory patients); median follow-up was 17.2 months. Median PFS was not reached (1-year PFS rate 75.1%). The most common hematologic grade 3/4 treatment-emergent adverse event was neutropenia (62.5%). Grade 3/4 infections were reported in 31.3% of patients, including 13.4% with grade 3/4 pneumonia. These results demonstrate the safety and efficacy of pomalidomide-based therapy as early as second line in patients with RRMM, even immediately after lenalidomide failure, indicating that switching from the immunomodulatory agent class is not necessary.

Emerging immunotherapies in multiple myeloma

“…Daratumumab has also been combined with pomalidomide, based on phase Ib data 61 and a nonrandomized, multicohort multicenter phase II study. 62 With this drug's promising results in relapsed and refractory multiple myeloma, trials evaluating daratumumab in transplant ineligible patients with newly diagnosed multiple myeloma showed significantly improved overall response rates and progression free survival. In the MAIA trial, daratumumab was combined with lenalidomide and dexamethasone (not reached v 31.9 months).…”

“…In randomized phase III studies of relapsed and refractory multiple myeloma, daratumumab and dexamethasone were combined with bortezomib (median progression free survival 16.7 v 7.1 months),4344 lenalidomide (44.5 v 17.5 months),454647 carfilzomib (not reached v 15.8 months),48 showing significant improvements in overall response rates and progression free survival. Daratumumab has also been combined with pomalidomide, based on phase Ib data61 and a non-randomized, multicohort multicenter phase II study 62. With this drug’s promising results in relapsed and refractory multiple myeloma, trials evaluating daratumumab in transplant ineligible patients with newly diagnosed multiple myeloma showed significantly improved overall response rates and progression free survival.…”

How I Treat Relapsed and/or Refractory Multiple Myeloma

“…While randomized phase 3 data is awaited from the APOLLO study (NCT03180736) evaluating the benefit of adding daratumumab to pomalidomide and dexamethasone (Pd) in early RRMM, two phase 2 studies have demonstrated the strong efficacy of this combination. 5 , 6 In particular, the phase 2 MM-014 study enrolled patients with early RRMM with 1-2 lines of prior therapy. Among 84 lenalidomide-refractory patients, median PFS was 21.8 months, suggesting that durable responses can be attained even without a class switch away from IMiD-based therapy in patients progressing on lenalidomide.…”

Approaching the first relapse after autologous transplant in multiple myeloma

“…Treatment schema. References for suggested regimens: V‐Pom‐d,28,29 K‐Pom‐d, 30 D‐Pom‐d, 31 D‐V‐d, 32,33 K‐R‐d, 34 K‐Cy‐d, 35‐37 D‐R‐d, 38,39 Elo‐R‐d, 40 Ixa‐R‐d, 41 Pom‐Cy‐d, 42,43 D‐K‐d, 44 Sel‐V‐d 45 . *Regimens with phase 1/2 data…”

“…Median PFS for lenalidomide refractory patinets was 21.8 months. Out of 112 patients, 12 patients achieved ≥ CR including 3 patients with MRD negativity (10 −5 ) by NGS 31 …”