EPOCH-F: A Novel Salvage Regimen for Multiple Myeloma Prior to Reduced-Intensity Allogeneic Stem Cell Transplantation

Variation in baseline host immune status contributes to inconsistent donor engraftment and may impede maximal graft-versus-myeloma effects after reduced-intensity allogeneic stem cell transplantation (RI-alloSCT) for advanced multiple myeloma. We performed a phase II study to determine the efficacy of a novel salvage regimen, EPOCH-F, which was designed to provide immune depletion and disease control prior to RI-alloSCT, in 22 patients with advanced multiple myeloma. EPOCH is an infusional chemotherapeutic regimen consisting of etoposide, vincristine and adriamycin, with prednisone, cyclophosphamide and fludarabine and given in 21 day cycles prior to RI-alloSCT. Patients received at least 1 and no more than 5 cycles of EPOCH-F gudied by peripheral blood CD4+ T cell count. Pts achieving adequate lymphodepletion proceeded to RI-alloSCT; otherwise patients proceeded to RI-alloSCT after 5 cycles or if there was disease progression during EPOCH-F, regardless of CD4 count. Median age was 53 years (range, 36–65); median time from initial therapy to transplant was 12 months (range, 2–168). Median number of prior therapies was 2 (range, 1–8), while 63% had chemotherapy sensitive disease. 68% of patients had received a novel agent. Patients received a median of 3 cycles (range, 1–5) of EPOCH-F. Therapy was well tolerated with manageable toxicities, mostly hematologic. Neutropenia (grade IV) was the most common toxicity seen in 77% of the administered cycles with only 6 episodes of neutropenic fever. Median lymphocyte count decreased from 1423/μL (range, 335–2788) to 519/μL (range, 102–1420); CD4 count decreased from 320/μL (range, 130–1366) to 115/μL (range, 30–309). In 21 evaluable patients, the overall response rate to EPOCH-F was 22% and 68% had stable disease. 13% of patients achieved CR/nCR. Only 1 patient progressed while on therapy. 20 patients received allograft from HLA matched sibling donors and were evaluable for engraftment. Median Day 100 chimerism was 100% (range 60–100, mean 95). 70% of patients achieved ≥VGPR including CR/nCR, while CR/nCR was seen in 40% of the patients. Median overall survival was 46.1 months. 10 (50%) patients are currently alive. Acute GVHD (grade II–IV) was seen in 47% and chronic GVHD (grade III–IV) was seen in 52% of patients. Treatment-related mortality at 100 days was 5% and 30% at 60 months. EPOCH-F is an active regimen which facilitates consistent and rapid full donor engraftment following RI-alloHSCT from related donors in patients with advanced multiple myeloma.