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EPOCH-F: a novel salvage regimen for multiple myeloma before reduced-intensity allogeneic hematopoietic SCT.

ABSTRACT: There exists a need for effective salvage regimens for multiple myeloma patients being considered for reduced-intensity allogeneic hematopoietic SCT (RI-alloHSCT). We developed EPOCH-F, a regimen consisting of infusional etoposide, VCR and adriamycin with prednisone, CY and fludarabine to achieve both tumor control and host lymphocyte depletion to facilitate engraftment before RI-alloHSCT. In all, 22 multiple myeloma patients were treated with EPOCH-F before RI-alloHSCT. The median age was 53 years (range 36-65), and the median number of previous therapies was 2 (range 1-8). Patients received a median of three cycles (range 1-5) of EPOCH-F. Toxicities were primarily hematologic and manageable. Median lymphocyte counts decreased from 1423/?L (range 335-2788) to 519/?L (range 102-1420; P=0.0002). The overall response (?PR) to EPOCH-F was 22 with 13% achieving a CR/near-complete response (nCR); only 1 patient progressed while on therapy. A total of 20 patients underwent RI-alloHSCT. Median day +100 donor chimerism was 100% (range 60-100). In all, 70% of patients achieved very good partial response or better response after transplant; 40% of patients achieved CR/nCR. TRM at 100 days and 5 years was 5 and 30%, respectively. Median OS after RI-alloHSCT was 46.1 months. EPOCH-F provides disease control and host lymphocyte depletion with consistent full donor engraftment in multiple myeloma patients undergoing RI-alloHSCT.

SUBMITTER: Jamshed S

PROVIDER: S-EPMC6944431 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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EPOCH-F: a novel salvage regimen for multiple myeloma before reduced-intensity allogeneic hematopoietic SCT.

Jamshed S S Fowler D H DH Neelapu S S SS Dean R M RM Steinberg S M SM Odom J J Bryant K K Hakim F F Bishop M R MR

Bone marrow transplantation 20100726 5

There exists a need for effective salvage regimens for multiple myeloma patients being considered for reduced-intensity allogeneic hematopoietic SCT (RI-alloHSCT). We developed EPOCH-F, a regimen consisting of infusional etoposide, VCR and adriamycin with prednisone, CY and fludarabine to achieve both tumor control and host lymphocyte depletion to facilitate engraftment before RI-alloHSCT. In all, 22 multiple myeloma patients were treated with EPOCH-F before RI-alloHSCT. The median age was 53 ye ...[more]

PMID: 20661232

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Project description:Allogeneic hematopoietic stem cell transplantation for patients with a hemoglobinopathy can be curative but is limited by donor availability. Although positive results are frequently observed in those with an HLA-matched sibling donor, use of unrelated donors has been complicated by poor engraftment, excessive regimen-related toxicity, and graft-versus-host disease (GVHD). As a potential strategy to address these obstacles, a pilot study was designed that incorporated both a reduced-intensity conditioning and mesenchymal stromal cells (MSCs). Six patients were enrolled, including 4 with high-risk sickle cell disease (SCD) and 2 with transfusion-dependent thalassemia major. Conditioning consisted of fludarabine (150 mg/m(2)), melphalan (140 mg/m(2)), and alemtuzumab (60 mg for patients weighing > 30 kg and .9 mg/kg for patients weighing <30 kg). Two patients received HLA 7/8 allele matched bone marrow and 4 received 4-5/6 HLA matched umbilical cord blood as the source of HSCs. MSCs were of bone marrow origin and derived from a parent in 1 patient and from an unrelated third-party donor in the remaining 5 patients. GVHD prophylaxis consisted of cyclosporine A and mycophenolate mofetil. One patient had neutropenic graft failure, 2 had autologous hematopoietic recovery, and 3 had hematopoietic recovery with complete chimerism. The 2 SCD patients with autologous hematopoietic recovery are alive. The remaining 4 died either from opportunistic infection, GVHD, or intracranial hemorrhage. Although no infusion-related toxicity was seen, the cotransplantation of MSCs was not sufficient for reliable engraftment in patients with advanced hemoglobinopathy. Although poor engraftment has been observed in nearly all such trials to date in this patient population, there was no evidence to suggest that MSCs had any positive impact on engraftment. Because of the lack of improved engraftment and unacceptably high transplant-related mortality, the study was prematurely terminated. Further investigations into understanding the mechanisms of graft resistance and development of strategies to overcome this barrier are needed to move this field forward.

Dataset Information

EPOCH-F: a novel salvage regimen for multiple myeloma before reduced-intensity allogeneic hematopoietic SCT.

Publications

EPOCH-F: a novel salvage regimen for multiple myeloma before reduced-intensity allogeneic hematopoietic SCT.

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