The European Commission has approved two combination therapies based on Celgene‘s Revlimid (lenalidomide) and Imnovid (pomalidomide), added to Velcade (bortezomib) and dexamethasone, for the treatment of some adult patients with multiple myeloma.
Revlimid, combined with Velcade and dexamethasone (RVd), is now indicated for the treatment of newly diagnosed, untreated adults who are not eligible for a stem cell transplant.
Additionally, Imnovid (sold as Pomalyst in the U.S.), added to Velcade and dexamethasone (PVd), was approved for adults who failed at least one prior line of therapy, including Revlimid.
Revlimid and Imnovid are two small molecule, oral medicines used in combination with dexamethasone as standard treatments for myeloma. They are both immunomodulatory agents (iMiDs), which means they drive the patient’s immune system to fight tumor cells, and can also attack cancer cells directly.
“The approval of these combination therapies marks a significant milestone for patients with multiple myeloma in Europe,” Nadim Ahmed, president of hematology and oncology for Celgene, said in a press release.
“With these new triplet regimens we hope to improve outcomes for both newly diagnosed patients as well as those who have relapsed or become refractory to first-line therapy. IMiD have brought significant benefit to multiple myeloma patients and we are committed to advancing our pipeline of novel myeloma treatments in order to ensure physicians and patients continue to have new treatment options available to fight this disease,” he added.
Approval in the EU follows a positive recommendation from the European Medicines Agency issued in April, based on the promising results from two Phase 3 trials testing the triple regimens.
The approval of the Revlimid triple combo was supported by positive data from SWOG S0777 (NCT00644228), a randomized, open-label trial designed to confirm the safety and efficacy of the Revlimid triple combo as a first-line therapy for untreated adults with multiple myeloma.
It enrolled 525 patients who were randomly assigned either the triple regimen Revlimid-Velcade-dexamethasone, given as eight cycles of 21 days, or the control double combo Revlimid-dexamethasone, given as six cycles of 28 days.
Trial data showed that adding Velcade prolonged patients’ lives without signs of disease worsening (42 months vs. 30 months) and overall survival (89 months vs. 67 months), compared with those who received Revlimid-dexamethasone only.
Likewise, the rates of overall and complete responses were higher in patients receiving the triple combination than in those in the control group — 82% vs. 72% for overall response, and 16% vs. 8% for complete response.
Moreover, the therapy’s safety was consistent with the well-established safety profiles for each individual agent in the combo.
“Determining first-line therapy is an important consideration in the overall treatment plan for patients with multiple myeloma,” said Thierry Facon, MD, professor of hematology at Lille University Hospital. “Since Revlimid in combination with dexamethasone is already a standard of care in multiple myeloma, we’re excited by the prospect of a new Revlimid-based triplet option for previously untreated patients who are not eligible for transplant.”
The EU’s approval of the Imnovid combo was based on positive results from OPTIMISMM, a randomized, open-label trial (NCT01734928) comparing the safety and efficacy of Imnovid triple regimen with Velcade-dexamethasone, as an early line of therapy in adults with multiple myeloma who failed at least one prior therapy.
This study enrolled 559 patients who received either the triple Imnovid combo, or the combo without Imnovid, that is Velcade and dexamethasone, which served as the control group. Most patients in the trial failed to respond to their last anti-myeloma treatment, including about 70% who were refractory to Revlimid.
Trial data showed the triple Imnovid combination therapy significantly increased the time patients lived without disease progression compared with those in the control group (11.2 months vs. 7.1 months), effectively reducing the risk of disease progression by 39%.
The safety of the Imnovid triplet was consistent with the well-established safety profiles of each individual agent.
“Today’s approval for use of the Imnovid-containing triplet, PVd, as early as first relapse, underscores the potential clinical benefit this regimen can provide to patients following a prior treatment including Revlimid,” said Meletios Dimopoulos, MD, professor and chairman of the clinical therapeutics department at the University Athens School of Medicine.
“Revlimid-based regimens are often used as a standard of care in newly diagnosed multiple myeloma patients, and there is a growing patient population who become refractory to Revlimid and need proven treatment options.”
In the U.S., none of the triple regimens are approved yet.