Eighty-five percent of patients with relapsed/refractory multiple myeloma (MM) achieved a partial remission (PR) or better (primary endpoint) when cyclophosphamide was added to pomalidomide and dexamethasone (PCD) treatment, according to results of a phase II trial presented at the 2017 ASH Annual Meeting. In addition, 92 percent of patients were able to proceed to autologous hematopoietic cell transplantation (ACHT), reported lead author Laurent Garderet, MD, PhD, of the Service d’Hématologie et Thérapie Cellulaire, Hôpital Saint-Antoine in Paris, France.
“Our goal was to find an effective salvage regimen to induce new remission in patients relapsing after exposure to lenalidomide and bortezomib, to proceed to AHCT,” Dr. Garderet said, adding that the results he presented were “sufficiently promising to justify further studies of the PCD regimen.”
The multicenter, open-label trial enrolled 100 patients (median age = 62 years; range = 39-70 years) between April 2014 and February 2017. All patients had MM that had relapsed after firstline treatment, consisting of lenalidomide, bortezomib, and dexamethasone (RVD) induction and consolidation therapy, plus lenalidomide maintenance for one year (arm A; n=50). The other half had undergone upfront AHCT after the induction phase as part of the initial protocol (arm B; n=50).
At first relapse, participants received PCD in 28-day cycles, consisting of:
- pomalidomide 4 mg on days 1-21
- cyclophosphamide 300 mg on days 1, 8, 15, and 22
- dexamethasone 40 mg on days 1-4 and 15-18
Patients also received four re-induction cycles with PCD. Patients in arm A who were responding to treatment could undergo AHCT and receive two additional cycles of PCD; in arm B, patients received five cycles of PCD. Maintenance therapy consisted of pomalidomide plus dexamethasone until disease progression.
The median time from diagnosis to first relapse was 3.6 years (range = 3.1-4.3 years), and 97 percent of patients had an Eastern Cooperative Oncology Group performance status score of 0 or 1. Fifteen percent of patients had high-risk cytogenetics [t(4-14), del17p, and/or t(14-16)], and most (78%) had an International Staging System score of I.
By July 4, 2017 (the planned intermediate analysis data cutoff), 97 patients had received four cycles of PCD and were evaluable for intermediate analysis.
Eighty-two patients responded to treatment, for an objective response rate of 85 percent. This included one complete remission (1%), 32 very good PRs (33%), and 49 PRs (51%). Three patients had stable disease (3%) and six had progressive disease (6%). Patients responded within a median of 28 days (range = 27-55 days).
Forty-five of 48 (94%) transplant-naïve patients in arm A were able to undergo planned AHCT, while seven patients in arm B received a second AHCT.
“The toxicity was mostly hematologic and manageable,” Dr. Garderet reported. Grade 3/4 adverse events (AEs) were reported by 72 of the 100 patients who received the study drugs (72%), the most common of which were hematologic toxicities (61%, including neutropenia [53%], lymphopenia [36%], anemia [6%], and thrombocytopenia [5%]) and infection (8%, including pneumonia [63%]). No patients reported grade 3/4 peripheral neuropathy.
Six patients (6%) discontinued one of the study drugs, and dose reductions were required with similar frequency for each of the three drugs (38% of patients for pomalidomide, 35% for cyclophosphamide, and 46% for dexamethasone). Reasons for dose reductions included AEs/serious AEs (77%, 70%, and 71%, respectively), omission (13%, 13%, and 9%), and “other” (10%, 17%, and 20%).
“The all-oral combination of PCD was efficacious at first relapse following RVD,” the authors reported. However, the study is limited by its lack of a comparator arm and small patient population. “These results should be compared to those of other pomalidomide and dexamethasone-based secondline therapies,” Dr. Garderet added.
The authors report financial relationships with Celgene, the manufacturers of pomalidomide.
Garderet L, Kuhnowski F, Mary JY, et al. A multicenter open label phase II study of pomalidomide, cyclophosphamide and dexamethasone in relapse multiple myeloma patients initially treated with lenalidomide, bortezomib and dexamethasone. Abstract #837. Presented at the 2017 American Society of Hematology Annual Meeting, Atlanta, GA, December 11, 2017.