Introduction Infusional chemotherapies remain vital yet under-studied in multiple myeloma (MM). They continue to serve important roles in therapy with their use in rapid cytoreduction for debulking, as salvage therapy in relapsed-refractory disease, and as bridge to definitive treatment. Despite emergence of novel agents, the use of traditional multi-agent infusional regimens such as DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin) and V(T)D-PACE (bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide) remain critical in select clinical scenarios. Limited data exists regarding current use and the associated outcomes of infusional chemotherapy in the modern-day treatment landscape, and to date no extensive head-to-head comparisons between infusional chemotherapy regimens have been made. In this single-center study, we characterize the real-world application and clinical outcomes of infusional chemotherapy regimens in MM with the goal of informing future treatment strategies.

Methods Patients who underwent treatment for biopsy-confirmed diagnosis of MM or plasma cell leukemia between January 2018 and May 2025 at a northeastern university cancer center were identified. Data points were stratified by chemotherapy regimen and further described by purpose of regimen, line of therapy (LOT), timing of definitive therapy (including CAR-T, BiTE, and autologous stem cell transplantation, also known as ASCT), and patient demographics including ISS/RISS prior to therapy and ethnicity. International Myeloma Working Group (IMWG) criteria was used to assess response to therapy. Overall response rate (ORR) was defined as partial response to treatment or better. Progression free survival (PFS) was measured in months from start of therapy to progression.

Results A total of 26 lines of therapy were identified among 14 patients: 4 CED, 7 (V)(T)-DCEP, 6 V(T)D-PACE, 6 HD CY, 1 Hyper-CVAD, 1 Hyper-CDT, 1 CPD. 73.1% of LOT were administered to males, 84.6% to Caucasians (11.5% to nonwhite Hispanic, 3.8% to other), and median age was 65 years, mean 61.8 years (range 39-70). The majority of LOTs were administered in patients with ISS/RISS stage II disease (52.0%) and for debulking (53.8%). (V)(T)-DCEP was most commonly utilized, was used as a bridge to definitive therapy in 71.4% of cases, and resulted in mean ORR 42.9% and mean PFS 7.2 months. V(T)D-PACE resulted in ORR of 66.7% and mean PFS of 3.9 months and was used for debulking in 66.7% of cases. CED had a mean ORR of 25.0% and mean PFS 4.6 months. HD CY was almost exclusively used for debulking (83.3% of LOT), had an ORR of 50%, and mean PFS 14.3 months. Sample size was too small for Hyper-CVAD, Hyper-CDT, or CPD to determine adequate estimates of ORR or PFS. When combining cyclophosphamide-etoposide-dexamethasone regimens, with or without bortezomib, thalidomide, or cisplatin, mean ORR was 36.4% with mean PFS 6.4 months.

Conclusion Additional studies are required to further describe the utility of infusional chemotherapy regimens in the present day. These regimens continue to be valuable in providing rapid cytoreduction or as a bridge to definitive therapy. Larger sample sizes are required in order to perform statistical analysis on subgroups to better characterize differences in therapy with respect to progression free survival, overall response rate, and time to response.

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2025
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