Pomalidomide for multiple myeloma

Abstract

Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of ‘novel agents’: proteasome inhibitors (first-in-class bortezomib) and immunomodulatory compounds (IMiDs; first-in-class thalidomide and lenalidomide). However, the vast majority – if not all – of patients with MM ultimately end up being refractory to all existing drugs, including these efficient novel agents. There is a clear unmet medical need in this situation, which warrants the development of the next generation of proteasome inhibitors and IMiDs, as well as new drug classes. This drug profile focuses on pomalidomide, the next generation IMiD, recently approved by the US FDA and the EMA for patients with relapsed or refractory MM who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy.

Keywords::

• IMiDs
• immunomodulation
• multiple myeloma
• pomalidomide
• relapse refractory

Financial & competing interests disclosure

T Facon and X Leleu have received honoraria and been on Advisory Boards for Celgene, Amgen, Janssen, Takeda and LeoPharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Pomalidomide is the most recently developed immunomodulatory compound.

• Pomalidomide exerts three primary effects: potent direct anti-myeloma activity, inhibition of stromal cell support and immune modulation.

• Pomalidomide’s efficacy is greatly synergistic with dexamethasone.

• Pomalidomide is efficient even in patients refractory to both lenalidomide and bortezomib, patients so far characterized by a very poor outcome.

• Pomalidomide was recently approved by the US FDA and the EMA for use alone (USA) or in combination with dexamethasone in patients with relapsed and refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy (within 60 days after completion of the last therapy for USA).

• The recommended dose schedule is 4 mg daily for 21 of 28 days, orally. Dexamethasone should be given at 40 mg weekly (20 mg for patients >75 years). Treatment is given until evidence of disease progression or unacceptable toxicity. Thromboprophylaxis is mandatory.

• Pomalidomide appears to be efficient and safe without dose adaptation to renal function to a certain degree, but this finding needs to be confirmed.

• Its safety profile is highly favorable, with mainly hematological toxicities that can easily be managed – combination with many anti-myeloma drugs is therefore feasible.

• Pomalidomide-based combinations are under investigation and preliminary results are promising.