Patients eligible for transplant

EMA CHMP grants positive opinion to dara-VTd combination for patients with newly diagnosed, transplant eligible multiple myeloma

The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion on the combination of daratumumab (dara), bortezomib (V), thalidomide (T) and dexamethasone (d, dara-VTd) for patients with newly diagnosed multiple myeloma (NDMM) who are eligible for autologous stem cell transplant (ASCT).1 The United States (U.S.) Food & Drug Administration (FDA) approved the dara-VTd combination in the same setting earlier this year in September 2019.2

The decisions of the EMA and FDA are based on the results of part one of the phase III CASSIOPEIA trial, presented during the American Society of Clinical Oncology (ASCO) meeting by Professor Philippe Moreau, earlier this year.3

CASSIOPEIA3,4

CASSIOPEIA is a phase III randomized trial comparing dara-VTd (n= 543) to VTd (n= 542) alone in patients with NDMM who are eligible for ASCT. At a median follow-up of 18.8 months, the rate of stringent complete response (sCR) was higher in the dara-VTd arm (29%) compared to VTd alone (20%). Measurable residual disease (MRD) negative rates were also higher in the dara-VTd group (64%) compared to the VTd arm (44%). Progression-free survival (PFS) at 18 months was 93% with dara-VTd versus 85% with VTd. This equated to a 53% reduction in the risk of progression or death. Median overall survival was not reached in either arm, with a 24-month OS rate of 97% with dara-VTd and 93% with VTd. The safety profile of the quadruplet regimen was equivalent to the drugs when given as single agents or combination therapies. Read more about the results of part one of the CASSIOPEIA trial here.3

Part two of the CASSIOPEIA trial is ongoing, with patients who achieve a response to induction and consolidation being re-randomized to maintenance with daratumumab (16mg/kg every eight weeks for up to two years), or observation. The primary endpoint of part two is post-maintenance progression-free survival.4

References
  1. European Medicines Agency. Darzalex. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/darzalex-0. Published; December 12 2019, [Accessed  December 13 2019]
  2. Healio: FDA approves Darzalex-based combination for first-line multiple myeloma treatment. https://www.healio.com/hematology-oncology/myeloma/news/online/%7Bd8139b99-2bbd-4a55-8d27-10549d392456%7D/fda-approves-darzalex-based-combination-for-first-line-multiple-myeloma-treatment. Published; September 26 2019, [Accessed  December 13 2019]
  3. Moreau P. et al., Phase 3 randomized study of daratumumab + bortezomib/thalidomide/dexamethasone (D-VTd) vs VTd in transplant-eligible newly diagnosed multiple myeloma: CASSIOPEIA Part 1 results; 2019. Oral Abstract #8003American Society of Clinical Oncology meeting 2019, Chicago, US
  4. ClinicalTrials.gov. A study to evaluate daratumumab in transplant eligible participants with previously untreated multiple myeloma (Cassiopeia). https://clinicaltrials.gov/ct2/show/NCT02541383. Updated October 29, 2019. Accessed December 2019 13
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