Pomalidomide plus low-dose dexamethasone in relapsed refractory multiple myeloma after lenalidomide treatment failure

David S Siegel, Gary J Schiller, Kevin W Song, Richy Agajanian, Keith Stockerl-Goldstein, Hakan Kaya, Michael Sebag, Christy Samaras, Ehsan Malek, Giampaolo Talamo, Christopher S Seet, Jorge Mouro, William E Pierceall, Faiza Zafar, Weiyuan Chung, Shankar Srinivasan, Amit Agarwal, Nizar J Bahlis, David S Siegel, Gary J Schiller, Kevin W Song, Richy Agajanian, Keith Stockerl-Goldstein, Hakan Kaya, Michael Sebag, Christy Samaras, Ehsan Malek, Giampaolo Talamo, Christopher S Seet, Jorge Mouro, William E Pierceall, Faiza Zafar, Weiyuan Chung, Shankar Srinivasan, Amit Agarwal, Nizar J Bahlis

Abstract

Patients with relapsed/refractory multiple myeloma (RRMM) for whom the benefits of lenalidomide have been exhausted in early treatment lines need effective therapies. In cohort A of the phase 2 MM-014 trial, we examined the safety and efficacy of pomalidomide plus low-dose dexamethasone immediately after lenalidomide-based treatment failure in patients with RRMM and two prior lines of therapy. Pomalidomide 4 mg was given on days 1 to 21 of 28-day cycles. Dexamethasone 40 mg (20 mg for patients aged >75 years) was given on days 1, 8, 15 and 22 of 28-day cycles. The primary endpoint was overall response rate (ORR), and secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. The intention-to-treat population comprised 56 patients; all received prior lenalidomide (87·5% lenalidomide refractory) and 39 (69·6%) received prior bortezomib. ORR was 32·1% (28·2% in the prior-bortezomib subgroup). Median PFS was 12·2 months (7·9 months in the prior-bortezomib subgroup). Median OS was 41·7 months (38·6 months in the prior-bortezomib subgroup). The most common grade 3/4 treatment-emergent adverse events were anaemia (25·0%), pneumonia (14·3%) and fatigue (14·3%). These findings support earlier sequencing of pomalidomide-based therapy in lenalidomide-pretreated patients with RRMM, including those who have become refractory to lenalidomide. Trial registration: www.ClinicalTrials.gov identifier NCT01946477.

Keywords: dexamethasone; lenalidomide; multiple myeloma; pomalidomide; refractory.

© 2019 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
CONSORT flow diagram of cohort A of MM‐014. Cohort A enrolled 56 patients.
Figure 2
Figure 2
ORR subgroup analysis. The dashed vertical line indicates 32·1%, which was the ORR (primary study endpoint) in the ITT population. ORR was mostly similar regardless of subgroup. aOne patient had creatinine >176·8 μmol/l. ECOG PS, Eastern Cooperative Oncology Group performance status; ITT, intention‐to‐treat; LCL, lower control limit; LEN Tx, lenalidomide treatment; ORR, overall response rate; R‐ISS, revised International Staging System; SCT, stem cell transplantation; UCL, upper control limit.
Figure 3
Figure 3
Pomalidomide treatment duration by best response. Median duration of pomalidomide treatment was 12·7 months in patients who achieved ≥PR, 12·3 months in patients who achieved ≥MR, 10·8 months in patients who achieved MR and 3·8 months in patients with SD. MR, minimal response; PR, partial response; SD, stable disease.
Figure 4
Figure 4
Progression‐free survival in the ITT population and prior‐bortezomib subgroup. Median PFS was 12.2 months in the ITT population and 7.9 months in the prior‐bortezomib subgroup. BORT, bortezomib; ITT, intention‐to‐treat; PFS, progression‐free survival.

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