NICE Issues Recommendations for Pomalidomide in Multiple Myeloma Previously Treated with Lenalidomide and Bortezomib

It is recommended as an option for treating multiple myeloma in adults at third or subsequent relapse

On 11 January 2017, the NICE announced that pomalidomide, in combination with low‑dose dexamethasone, is recommended as an option for treating multiple myeloma in adults at third or subsequent relapse. It is recommended after 3 previous treatments including both lenalidomide and bortezomib and only when the company provides pomalidomide with the discount agreed in the patient access scheme.

There is a clear unmet need in the current treatment pathway, because very few options are available after using existing NICE‑recommended treatments ( thalidomide, bortezomib and lenalidomide).

The appraisal committee understood that the clinical experts valued pomalidomide because it was a clinically effective, oral, well‑tolerated treatment. The committee heard that quality of life is an especially important consideration at this stage of the pathway because of the accumulation of toxicities over multiple lines of therapy. The clinical experts stated that pomalidomide provided a well‑tolerated treatment option.

The company presented evidence from MM‑003, a phase III, open‑label trial that compared pomalidomide plus low‑dose dexamethasone with high‑dose dexamethasone alone. The appraisal committee agreed that high‑dose dexamethasone was a reasonable proxy for the clinical effectiveness of conventional chemotherapy.

Because there was no direct evidence other than for conventional chemotherapy, the company selected individual treatment arms from available studies and ran separate analyses comparing pomalidomide and low‑dose dexamethasone with each of the comparators.

The appraisal committee heard that patients in the trial were younger than typically seen in clinical practice, but the clinical experts' experience in practice suggests that older patients experience similar outcomes with pomalidomide.

The appraisal committee heard from the clinical experts that although high‑dose dexamethasone was appropriate when MM‑003 was started, it no longer represents an option for active treatment in England.

The indirect comparisons were associated with considerable uncertainty and the committee recognised that the company had presented the best evidence available. The committee concluded that the results based on the company's indirect comparisons were acceptable for its decision‑making.

Estimate of the size of the clinical effectiveness including strength of supporting evidence

Pomalidomide and low‑dose dexamethasone compared with high‑dose dexamethasone:

  • Progression‑free survival gain of 1.8 months in favour of pomalidomide.
  • Overall survival gain between 4.6 months and 7.0 months in favour of pomalidomide.

Pomalidomide and low‑dose dexamethasone compared with bendamustine:

  • Progression‑free survival benefit of 4.2 months compared with 3.3 months in favour of pomalidomide.
  • Overall survival gain of 16.5‑month compared with 8.1 months in favour of pomalidomide.

Pomalidomide and low‑dose dexamethasone compared with panobinostat:

  • Progression‑free survival benefit of 4.1 months compared with 5.3 months for panobinostat.
  • Overall survival benefit of 12.4 months compared with 17.5 months for panobinostat.

The company presented an economic model comparing pomalidomide and low‑dose dexamethasone with: conventional chemotherapy; bendamustine with thalidomide and dexamethasone; and panobinostat with bortezomib and dexamethasone.

The most plausible incremental cost-effectiveness ratio (ICERs) for pomalidomide with low‑dose dexamethasone compared with conventional chemotherapy and bendamustine with thalidomide and dexamethasone were below 50,000 GBP per QALY gained, and the appraisal committee concluded that pomalidomide meets the end‑of‑life criteria compared with bendamustine and conventional chemotherapy.

The end‑of‑life criterion for an additional 3 months survival gain was not met for the comparison with panobinostat with bortezomib and dexamethasone and the ICERs reflected 'savings per QALY lost'; that is, pomalidomide was less effective but less costly. The appraisal committee noted that the savings per QALY lost for pomalidomide compared with panobinostat were high enough for it to be considered a cost‑effective use of NHS resources without applying the end‑of‑life criteria. The appraisal committee concluded that it could recommend pomalidomide with low‑dose dexamethasone for treating relapsed and refractory multiple myeloma at third or subsequent relapse.