Plitidepsin
Treatment of relapsed/refractory multiple myeloma in patients refractory to a proteasome inhibitor and an immunomodulatory drug (third-line setting) or in patients who have received at least three prior treatment regimens including both a proteasome inhibitor and an immunomodulatory drug (fourth-line setting).
Decisions on record
- Meeting Mar 2020 Not recommended Plitidepsin, in combination with dexamethasone, is indicated for the treatment of patients with relapsed and refractory multiple myeloma (RRMM) who have received at least two prior treatment regimens, including both a proteosome inhibitor (PI) and an immunomodulator (IMiD).
- Meeting Jul 2019 Not recommended Multiple myeloma
Access path
- Jul 2019Not recommended
vs Pomalidomide with dexamethasone (third-line); dexamethasone…
- Mar 2020Not recommended
Marginal clinical benefit in PFS (median increase of 0.9-3 months depending on analysis), significant increase in…
From the public summary
The PBAC did not recommend the listing of plitidepsin in patients who are refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) (third-line setting) or in patients who have received at least three prior treatment regimens including both a PI and an IMiD (fourth-line setting).PSD · Mar 2020
The PBAC noted the large number of consumer comments describing the desire for another treatment option in this setting.PSD · Mar 2020
Cost-minimisation analysis (third-line setting) The resubmission presented a revised CMA based on the indirect comparison between plitidepsin + Dxm and pomalidomide + Dxm.PSD · Mar 2020
The ESC considered that the appropriateness of a CMA was not adequately supported as no new evidence was presented in the resubmission and the claim of non-inferior efficacy and safety between plitidepsin + Dxm and pomalidomide + Dxm remained uncertain.PSD · Mar 2020
Plitidepsin + Dxm compared with Dxm (fourth-line setting) The resubmission described plitidepsin + Dxm as superior in terms of effectiveness compared with Dxm monotherapy (fourth-line setting). This was unchanged from the July 2019 submission.PSD · Mar 2020
The resubmission provided an updated safety claim, describing plitidepsin + Dxm as inferior compared with Dxm monotherapy. The PBAC agreed with the ESC and considered that the claim of inferior safety was supported by the evidence presented from the ADMYRE trial.PSD · Mar 2020
The PBAC noted and welcomed the input from individuals (49), health care professionals (2) and organisations (4) via the Consumer Comments facility on the PBS website. The comments from the individuals described the desire for another treatment option to become available on the PBS and concerns regarding toxicity and side effects.PSD · Mar 2020
The comments from the health care professionals were supportive of providing PBS- subsidised access to treatment for patients, describing their experience with plitidepsin and how patients have benefitted from treatment.PSD · Mar 2020
Cost-effectiveness
ICER values are redacted (shown as '$''''''''''''') in the public document. The resubmission presented a cost-minimisation analysis (third-line) and cost-utility analysis (fourth-line) with base case ICER redacted.
Decision context
PopulationPatients with relapsed/refractory multiple myeloma who are refractory to a proteasome inhibitor and an immunomodulatory drug (third-line) or have received at least three prior treatment regimens including both a proteasome inhibitor and an immunomodulatory drug (fourth-line), treated in combination with dexamethasone.
Risk sharingSpecial Pricing Arrangements (SPA) acknowledged as may be required; i-access risk management program registration required for continuing treatment.
Why it was knocked back
- Marginal clinical benefit in PFS (median increase of 0.9-3 months depending on analysis), significant increase in adverse events, uncertain non-inferiority claim against pomalidomide + Dxm, insufficient safety data for comparison with pomalidomide, issues with economic model methodology (crossover adjustment, utility values, time-to-treatment-failure estimation, KM data application), ICER threshold concerns given substantial toxicity and minor additional benefit
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2020 | Not recommended | Pomalidomide (third-line setting); Dexamethasone (fourth-line setting) | — | RCT · PFS |
| Jul 2019 | Not recommended | Pomalidomide with dexamethasone (third-line); dexamethasone monotherapy (fourth-line) | — | RCT · PFS |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| ADMYRE | Ph 3 | 255 | Progression Free Survival (PFS) as Per Intention-to-treat (ITT) | completed |
Consumer voice
Forty-nine individuals expressed desire for plitidepsin as a treatment option on the PBS and raised concerns about toxicity and side effects. Two healthcare professionals supported PBS-subsidised access, describing positive patient outcomes with plitidepsin, while four organisations (Myeloma Australia, Leukaemia Foundation, South East Myeloma Support Group, and Rare Cancers Australia) provided var
The comments from the individuals described the desire for another treatment option to become available on the PBS and concerns regarding toxicity and side effects. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label equal than PBS population — Both texts describe identical populations: third-line (refractory to PI and IMiD) or fourth-line (≥3 prior regimens including PI and IMiD) with dexamethasone.