Comparison of Debulking Regimens (EPOCH and DCEP) for the Treatment of Relapsed or Refractory Multiple Myeloma

Background: Despite recent advancements in management, relapsed and refractory multiple myeloma (RRMM) remains challenging to treat. At the time of aggressive relapse, a debulking regimen consisting of traditional infusional chemotherapy is often necessary to gain control of the disease and bridge patients to continuous treatment-based therapies. These RRMM regimens have commonly included: dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) as well as variations of bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide and etoposide (VTD-PACE). These aggressive combinations are limited to a few cycles and are associated with severe toxicities including myelosuppression, infection, neuropathy, and renal dysfunction. Of particular interest is RRMM patients with anaplastic histology which is rare and associated with poor prognosis when managed with standard RRMM therapy. Case reports have demonstrated successful use of the lymphoma combination regimen etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH) in patients with anaplastic multiple myeloma (Ichikawa et al. Leuk Res Rep 2021; Ichikawa et al. J Clin Exp Hematop 2018). There is very limited data to support the safety or efficacy of EPOCH in RRMM. We were motivated to evaluate our patients treated with EPOCH or DCEP in RRMM with and without anaplastic histology.

Methods: This single-center study includes all RRMM patients treated with either DCEP or EPOCH at the University of Miami Hospital and Clinics, Sylvester Comprehensive Cancer Center between June 1, 2021, and data cutoff (June 21, 2024). The primary aim was to investigate the safety and efficacy of EPOCH. Adverse events were graded according to CTCAE V5.0 and responses were assessed using the IMWG uniform response criteria. P-values were calculated using Fisher's Exact test.

Results: At the time of data cutoff, 41 patients received DCEP and 14 received EPOCH. Patients who received EPOCH vs DCEP had a median age of 61.5 vs 63 years, of which 7% vs 12% were Black, and 71% vs 37% of Hispanic ethnicity, respectively. The median lines of prior therapy for EPOCH vs DCEP were 5 vs 5, while the presence of high-risk disease as defined as the presence of del17p, t(4;14) or t(14;16) was 54% vs 50%, respectively. Of the patients who received EPOCH vs DCEP, 79% vs 44% had extramedullary disease with soft tissue involvement, 50% vs 15% had ≥ 90% bone marrow plasmacytosis, and 86% vs 46% had anaplastic plasma cell morphology, respectively. Serious adverse events requiring readmission to the hospital or prolongation of hospitalization occurred in 43% of patients receiving EPOCH and 51% of patients receiving DCEP. Grade ≥3 hematologic events included thrombocytopenia (79%), anemia (86%), and neutropenia (86%) in patients receiving EPOCH and 79%, 76%, and 90% in patients receiving DCEP, respectively. Moreover, bleeding events occurred in 21% of patients receiving EPOCH or DCEP. Documented infections were observed in 36% of patients in the EPOCH and 54% in the DCEP group. At the 1-year survival landmark, 36% of patients who received EPOCH and 33% of patients who received DCEP were alive. The majority of patients in the EPOCH arm (57%) received either autologous stem cell transplant, bispecific antibody or chimeric antigen receptor T-cell therapy as the next line of therapy. The overall response rate (ORR) was higher for EPOCH but did not reach statistical significance (69% vs 50%; p=0.3667). Among patients with anaplastic histology the best ORR was also higher for the EPOCH group but not statistically significant (64% vs 56%; p=0.7167).

Conclusions: Our findings suggest that EPOCH may be a reasonable alternative debulking option for patients with RRMM, particularly in patients with baseline renal or other organ dysfunction making administration of platinum-based chemotherapy challenging or with extensive extramedullary disease. Larger studies are needed to confirm and expand on our results in comparison to DCEP.

Kowalski:Pfizer: Consultancy. Diamond:Janssen: Honoraria. Hoffman:Syndax: Other: stock and other ownership interests. Maura:Sanofi: Consultancy, Honoraria; Medidata: Consultancy, Honoraria. Rosen:Janssen: Speakers Bureau. Verducci:Pfizer: Consultancy. Landgren:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Membership on independent data monitoring committees; Adaptive: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Membership on independent data monitoring committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Membership on independent data monitoring committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Membership on independent data monitoring committees; Theradex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Membership on independent data monitoring committees.; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Membership on independent data monitoring committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Membership on independent data monitoring committees. Kazandjian:MMRF: Honoraria; Aptitude Health: Honoraria; Bridger Consulting Group: Consultancy; Curio Science: Honoraria; Karyopharm Therapeutics: Honoraria, Research Funding, Speakers Bureau; Alphasights: Consultancy; Plexus: Honoraria; Dedham Group: Consultancy; MJH Life Sciences: Honoraria; Arcellx: Honoraria, Other: served on independent data monitoring committees (IDMC); Aperture Medical Technologies: Honoraria, Other: served on independent data monitoring committees (IDMC); Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; NCI/NIH, FDA, MMRF, DoD-PROMETHEUS (Murtha Cancer Center Research Program), Amgen, BMS/Celgene, Janssen,: Research Funding; MJH Life Sciences: Honoraria; BMS: Honoraria; Magnolia: Honoraria.

Combination EPOCH and DCEP for the treatment of relapsed or refractory multiple myeloma