Is There a Preferred Infusional Regimen for Patients with Relapsed/Refractory Multiple Myeloma?
Authors: Griffin Patrick T. , Ho Viet Q. , Fulp William , Nishihori Taiga , Shain Kenneth H. , Alsina Melissa , Baz Rachid 
Published: October 2019

Introduction:

Despite the impact of novel agents, many patients with multiple myeloma (MM) still require intensive infusional chemotherapy regimens, such as dexamethasone, cyclophosphamide, etoposide, cisplatin (DCEP), bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide and etoposide (VDT-PACE), or cyclophosphamide, vincristine, adriamycin, and dexamethasone (CVAD), especially in the setting of proliferative relapsed/refractory disease. To our knowledge, there are no published data comparing the different infusional regimens. Here, we present a retrospective analysis comparing the efficacy and safety of the three most commonly used MM salvage regimens in the era of novel agents.

Methods:

Patients with a diagnosis of relapsed/refractory MM who received one of the three chemotherapy regimens (DCEP, VDT-PACE, or CVAD) between 01/2005 and 12/2013 were identified through the Moffitt Total Cancer Care Database. Clinical variables were abstracted from the patient records. The IMWG criteria were used to assess response. Transplant eligibility was determined based on the assessment of the treating physician. Progression-free survival (PFS) and overall survival (OS) for each group were estimated from the initiation of salvage therapy using the Kaplan-Meier method. Multivariate predictors of survival were assessed using the Cox proportional hazards model by backward elimination.

Results:

A total of 107 patients receiving one of the 3 regimens for relapsed/refractory MM were identified (DCEP 52, VDT-PACE 22, CVAD 33). Relevant patient characteristics, treatment outcomes, and adverse events are described in Table 1. Prior therapy history was similar between the 3 groups in regard to lenalidomide (77.6%), bortezomib (88.8%), and autologous transplant (53.3%). An analysis of treatment outcomes revealed no statistically significant differences in response, PFS, or OS between the 3 regimens. There appeared to be a trend towards more FN in the VDT-PACE group, as well as prolonged hospitalization in the CVAD group. On multivariate analysis of the entire cohort, transplant eligibility prior to salvage treatment was the only significant predictor of OS (HR 0.22, p<0.001), whereas the treatment regimen was not significant (p=0.411). In fact, for the non-transplant eligible population, the median OS was only 3.09 months (95% CI, 2.17-4.02), versus 16.70 months (95% CI 11.45-21.97) for those patients deemed transplant eligible. On multivariate analysis of the transplant eligible population, performance status (HR 2.10, p=0.012) and extramedullary disease (HR 3.71, p=0.002) were significantly correlated with OS.

Conclusions:

In this retrospective analysis, there were no statistically significant differences in outcomes between the three MM salvage regimens. Of note, the more intensive regimen, VDT-PACE, did not demonstrate superior disease response or survival. For patients in whom a bridge to transplant was not planned, infusional chemotherapy was associated with poor outcomes, and should not be considered in that setting given the significant toxicities. There was a trend towards fewer adverse events in the DCEP treated patients. Abstract 4757. Table 1.Characteristics, N (%) DCEP n=52 VDT-PACE n=22 CVAD n=33 p-value Age (yrs), median (range)57.6 (43-73)54.5 (29-68)56.9 (41-73)0.054Creatinine (mg/dL), median (range)0.90 (0.6-2.8)1.25 (0.6-6.6)2.20 (0.6-12.9)<0.001Extramedullary Disease, N (%)15 (28.8)7 (31.8)3 (9.1)0.056Circulating Plasma Cells >5%, N (%)4 (7.7)4 (18.2)7 (21.2)0.169High Risk Cytogenetics, N (%)18 (34.6)6 (27.3)8 (24.2)0.803+1q219 (17.3)1 (4.5)2 (6.1)t(4;14)5 (9.6)02 (6.1)-17p11 (21.2)6 (27.3)4 (12.1)Prior Regimens, N (%)3 (1-9)3 (1-13)3 (1-7)0.514Transplant Eligible, N (%)32 (61.5)14 (63.7)17 (51.5)0.578OutcomesVGPR or better, N (%)9 (17.3)7 (31.8)4 (12.1)0.284PR or better, N (%)27 (51.9)16 (72.7)16 (48.5)0.386Successful Bridge to Transplant, N (%)20/32 (62.5)8/14 (57.1)11/17 (64.7)0.907Median PFS, mo. (95% CI)3.78 (1.96-5.60)4.54 (1.67-7.41)5.79 (2.10-9.48)0.801Median OS, mo. (95% CI)8.26 (5.52-10.99)8.52 (3.16-13.87)8.22 (0.00-18.46)0.835Adverse Events, N (%)Prolonged Hospitalization4 (7.7)1 (4.5)7 (21.2)0.084Re-Hospitalization for Adverse Event15 (29.4)8 (36.4)13 (40.6)0.563Febrile Neutropenia15 (29.4)11 (50.0)13 (39.4)0.230Treatment Related Mortality3 (5.8)1 (4.5)3 (9.1)0.762

Disclosures

No relevant conflicts of interest to declare.