Conference Correspondent

Ixazomib, Pomalidomide, and Dexamethasone Triplet Therapy in Patients with Double/Triple Refractory Myeloma

Conference Correspondent - Conference Correspondent, ASH 2016 - Multiple Myeloma

Triplet regimens combining an immunomodulatory agent, a proteasome inhibitor, and a steroid are often used to treat newly diagnosed and relapsed multiple myeloma (MM). Lenalidomide (LEN) is a backbone of many MM regimens in the frontline and relapsed settings; therefore, patients with relapsed/refractory (RR) MM are often LEN-refractory. This phase 1/2 study evaluates the combination of pomalidomide (POM), an oral immunomodulator, and ixazomib (Ix), an oral proteasome inhibitor, in patients with RRMM and high-risk cytogenetics.

Researchers sought to determine the maximum tolerated dose of Ix in combination with standard dose POM and dexamethasone (DEX) and to evaluate the antitumor activity of the triplet. The treatment regimen included 2 dose levels (3 mg and 4 mg) of Ix on days 1, 8, 15; POM 4 mg days 1-21; and DEX 40 mg days 1, 8, 15, 22, of a 28-day cycle. The study included patients with RRMM after >1 prior therapy who were LEN-refractory with grade 1 or no peripheral neuropathy (PN). Patients were treated until progression or unacceptable toxicity.

A total of 31 patients were evaluable for toxicity and response. Median age was 62 years, median time from diagnosis was 3.6 years, and patients had a median of 2 prior therapies. A total of 20 (63%) patients were double-refractory (to LEN and bortezomib) and 3 (9%) were triple-refractory to LEN, bortezomib, and carfilzomib.

Of 31 patients treated in phases 1 and 2, 45% achieved overall response (very good partial response [VGPR], n = 5; partial response, n = 9), and the clinical benefit rate was 81% (VGPR, n = 5; PR, n = 9; minimal response, n = 3; stable disease, n = 8).

Investigators concluded that the triplet regimen (Ix/POM/DEX) is a promising oral combination therapy in high-risk patients, given that more than 60% of patients were dual-refractory.

Krishnan A, et al. ASH 2016. Abstract 3316.

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