Paper Details

ABSTRACT

Background: Despite unprecedented advancements in the management of relapsed or refractory multiple myeloma (RRMM) in recent years, management of aggressive disease may still require a traditional chemotherapy debulking regimen to gain control of the disease. This aggressive and toxic approach facilitates the use of subsequent therapies that often achieve more durable responses with less toxicity, such as bispecific antibodies or chimeric antigen receptor T-cell therapy. Historical infusional chemotherapy based debulking regimens include: dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) as well as variations of bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide and etoposide (VTD-PACE). The toxicity of these combinations limit use to less than three cycles and myelosuppression, infection, neuropathy, and renal dysfunction can complicate management. RRMM patients with anaplastic histology represent a rare and unique population with a 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 are very limited data to support the safety or efficacy of EPOCH in RRMM (Kowalski et al. Blood 2024). The authors were motivated to review our single institution experience of patients treated with EPOCH or DCEP in RRMM with and without anaplastic histology.

Methods: This single-center retrospective 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 (July 30, 2026). 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, we identified 92 patients of whom 57 patients received DCEP and 35 received EPOCH. The median age for both groups was 62 years. In the EPOCH vs DCEP groups 20% vs 12% were Black race and 51% vs 39% of Hispanic ethnicity, respectively. The median lines of prior therapy for EPOCH vs DCEP were 5 (range 1-20) vs 5 (range 1-13), while the presence of high-risk disease as defined as the presence of del17p, t(4;14) or t(14;16) was 48% vs 51%, respectively. Among the patients who received EPOCH vs DCEP, 69% vs 44% had validated soft tissue extramedullary disease, 48% vs 52% had ≥ 60% bone marrow plasmacytosis, and 49% vs 39% had anaplastic plasma cell morphology, respectively. Among the DCEP group, 8 patients (14%) received a modified regimen without cisplatin due to renal impairment or peripheral neuropathy. The overall response rate (ORR) was higher for EPOCH when compared to DCEP (77% [95% CI 62.1% to 86.1%] vs 50% [95% CI 36.1% to 63.9%]; p=0.015). Serious adverse events requiring readmission to the hospital or prolongation of hospitalization occurred in 49% of patients receiving EPOCH and 54% of patients receiving DCEP. Grade ≥3 hematologic events included thrombocytopenia (74%), anemia (71%), and neutropenia (77%) in patients receiving EPOCH and 81%, 75%, and 91% in patients receiving DCEP, respectively. Moreover, bleeding events occurred in 14% of patients receiving EPOCH vs 18% of patients receiving DCEP. Documented infections were observed in 43% of patients in the EPOCH and 51% in the DCEP group. Febrile neutropenia specifically was less common in the EPOCH group (29% vs 46%). At the 1-year survival landmark, 48% of patients who received EPOCH and 41% of patients who received DCEP were alive. The majority of patients in the EPOCH arm (63%) received either autologous stem cell transplant, bispecific antibody or chimeric antigen receptor T-cell therapy as the next line of therapy.

Conclusions: In this retrospective analysis, EPOCH appears to be a reasonable alternative debulking option for patients with RRMM, particularly in patients with baseline organ dysfunction (e.g. renal) that complicates the use of platinum-based chemotherapy or in the setting of extensive extramedullary disease. Larger studies are needed to confirm these findings and rigorously compare EPOCH to DCEP prospectively.