Investigational Treatments for Multiple Myeloma

Paul G. Richardson, MD

Carlfilzomib

A number of presentations at ASH focused on carlfilzomib, a second-generation proteasome inhibitor designed to improve upon the efficacy of bortezomib with less peripheral neuropathy. One of the studies that stood out was a phase I/II trial showing that carlfilzomib, lenalidomide, and lowdose dexamethasone (CRd) was highly active and well-tolerated in patients with newly diagnosed multiple myeloma, achieving rapid responses. The study included 53 patients who received CRd in 28-day cycles with a carfilzomib dose of either 20 mg/m2 (n = 4), 27 mg/m2 (n = 13), or 36 mg/m2 (n = 36).

The partial response (≥50% disease reduction) rate was 94% following completion of at least 1 cycle and 100% after at least 4 cycles. All patients completing ≥12 cycles achieved very good partial response, defined as a 90% disease reduction. The combination treatment was welltolerated, with no reported grade 3 or 4 peripheral neuropathy.

Pomalidomide

Several oral presentations at ASH focused on pomalidomide. A phase I/II study examined pomalidomide in combination with cyclophosphamide and prednisone in patients with relapsed/ refractory multiple myeloma. In the phase II part of the study, 66% of the 29 evaluable patients achieved at least partial response. Among lenalidomide- refractory patients, 73% achieved at least partial response. The most common severe side effect was neutropenia, seen in 40% of patients. Other side effects were minimal.

A second phase I/II study compared pomalidomide alone versus pomalidomide plus low-dose dexamethasone in relapsed/refractory multiple myeloma Among the 221 patients enrolled in the phase II part of the trial, partial response was achieved in 34% treated with pomalidomide plus dexamethasone versus 13% in the pomalidomide alone arm. Median progression-free survival was 4.7 months and 2.7 months, respectively, for the 2 arms. Median overall survival was 16.9 months and 14 months, respectively. The most frequently reported severe side effect was neutropenia.

Jakubowiak AJ, Dytfeld D, Jagannath S, et al. Final results of a frontline phase I/II study of carfilzomib, lenalidomide, and low-dose dexamethasone in multiple myeloma. Blood. (ASH Annual Meeting Abstracts) 2011;118(21, abstr 631).

Palumbo A. Larocca A, Carella AM, et al. A phase I/II study of pomalidomide-cyclophosphamide-prednisone in patients with multiple myeloma relapsed/refractory to lenalidomide. Blood. (ASH Annual Meeting Abstracts) 2011;118(21, abstr 632).

Richardson PG, Siegel DS, Vij R, et al. Randomized, open label phase I/II study of pomalidomide alone or in combination with low-dose dexamethasone in patients with relapsed and refractory multiple myeloma who have received prior treatment that includes lenalidomide and bortezomib: phase II results. Blood. (ASH Annual Meet- Paul G. Richardson, MD ing Abstracts) 2011;118(21, abstr 634).