Carfilzomib in Combination with Dexamethasone, Cyclophosphamide, Etoposide, and Cisplatin (KDCEP) for the Treatment of Relapsed/Refractory Aggressive Plasma Cell Dyscrasias
Authors: Wagner Charlotte B , Julian Kelley , Bryan Baylee , Steinbach Mary Nicole , Shewan Samuel , Maxwell Lindsay , Vigil Meghan , Mohyuddin Ghulam Rehman , Godara Amandeep , McClune Brian , Sborov Douglas 
Published: December 2023

Background: Dexamethasone with Cyclophosphamide, Etoposide and Cisplatin (DCEP) is an effective regimen in aggressive relapsed/refractory MM (RRMM) with overall response rates (ORR) as high as 58% [Dadacaridou, M. et al JBUON 2007]. ORR is lower (35 - 45%) in patients (pts) exposed to novel therapeutics such as immunomodulatory agents (IMiD), proteasome inhibitors (PI), and anti-CD38 antibodies (mAb) [Park, Silvia et al Ann. Hematol 2014; Goldsmith, Scott et al. Blood2021]. The addition of bortezomib (V) to DCEP demonstrated ORR of 47% [Valla, Kelly et al. Blood 2014]. Due to common use of V front-line, most pts are V exposed by the time treatment for relapse is indicated; therefore, we began using carfilzomib (K) with DCEP. K has been utilized with DPACE with ORR of 77% [Alsouqi, A. et al. Clin Lymphoma Myeloma Leuk 2021], however an anthracycline may not be feasible in heavily pretreated pts. We present the first reported outcomes of RRMM pts treated with KDCEP.

Methods:This is a case series from the University of Utah Huntsman Cancer Institute of all consecutive pts treated with KDCEP from 2017-2022, conducted under IRB approval. Demographic, disease, treatment, and response data were retrospectively collected. Responses were assessed by IMWG criteria, and adverse events were graded by CTCAE v.5. Descriptive statistics were utilized; a Kaplan-Meier estimate was used for the time to event analysis.

Results:Six pts received KDCEP (Table 1). The median age was 63.5 years (range 47 - 73). All pts had ECOG performance status of 1-2, and 67% were male. Median prior treatment lines were 2.5 (range 2 - 7) with 33% undergoing prior autologous stem cell transplant (autoHCT). All pts were exposed to V with 67% refractory. Thirty-three percent had prior K exposure, however none were considered refractory to K, and 67% were refractory to a PI, IMiD and mAb. Two pts received KDCEP as chemo-mobilization prior to autoHCT. All pts had IgG or IgA disease with 67% having high risk cytogenetics (33% 17p del, 50% gain 1q21) and 1 pt had primary plasma cell leukemia. R-ISS stage at diagnosis was: stage 3 (n=2), stage 2 (n=1) unknown (n=3). All pts had baseline echocardiograms with ejection fractions prior to treatment ranging from 57 - 78%. Pts received K on Days 1 and 8 of each 28-day cycle, prophylactic growth factor, and standard antimicrobial prophylaxis. Two pts received 2 cycles, all others received 1. The overall response rate was 100% and included the following best responses: PR (n = 4), VGPR (n = 1), CR (n = 1). One patient that initially achieved a PR relapsed within 60 days and died awaiting enrollment on a clinical trial, however all other pts were successfully bridged to their next line of therapy. Five pts had MRD data available after treatment, each demonstrating detectable MRD. Median progression free survival was 6.7 months. Median time to ANC nadir was 11 days (range 9-14) and to ANC recovery, defined as ANC &gt; 1000/uL, was 18 days (range 14 - 23). Median time to platelet nadir was 12.5 days (range 9-23) and to platelet recovery, defined as platelets &gt; 100 k/uL, was 25 days (range 20 - NR). Median time to next cycle or treatment was 43 days (range 31-54). Sixty-seven percent of pts had a grade ≥ 3 toxicity including neutropenic fever (n=2), sepsis due to pseudomonas bacteremia (n=1), and septic thrombophlebitis (n=1). No cardiac toxicities or treatment related deaths were observed.

Discussion:In this cohort of heavily pre-treated pts who received KDCEP, ORR was high indicating the regimen is active in this population. KDCEP may be a viable option for RRMM pts, particularly in those who are triple class refractory or with high risk cytogenetic abnormalities. Our data suggests that KDCEP may be an effective regimen to bridge patients to the next line of therapy; however all patients should be monitored closely for infection.