Contemporary Use of VTD-PACE As Bridge Therapy in Patients with Heavily Pre-Treated Relapsed/Refractory Multiple Myeloma

Background:

Despite availability of novel agents, treatment options in relapsed or refractory multiple myeloma (RRMM) patients are limited. The safety and efficacy of VTD PACE (bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide) and VTD PACE-like regimens (VPLRs) have been evaluated at two institutions (Lakshman et al, Am J Hematol 2018 and Abdallah et al, Clinical Lymphoma, Myeloma and Leukemia 2021). In these studies, the median number of prior lines of treatment were 4 (Lakshman et al, Am J Hematol 2018) and 3 (Abdallah et al, Clinical Lymphoma, Myeloma and Leukemia 2021) with the majority of patients naïve to daratumumab and carfilzomib. Here, we present a retrospective analysis of safety and efficacy of VTD PACE in heavily pre-treated RRMM at Cleveland Clinic.

Methods:

Sixty-seven RRMM patients were identified who received at least one cycle of VTD PACE or VPLR from December 2014 to April 2022. Dose adjustments were made based on physician discretion, comorbidities, and organ function. Responses were evaluated using IMWG Uniform Response Criteria. Data collection included demographic information such as age at treatment, gender, risk category, as well as prior lines of therapy, chemotherapy dose adjustments, re-admission rate, incidence of febrile neutropenia, time to disease progression, and subsequent therapy. The primary endpoint was overall response rate (ORR) after cycle one (evaluated at day 28 +/- 14 days) and secondary endpoints included overall survival (OS), progression free survival (PFS), and re-admission rate following chemotherapy.

Results:

The median age at the start of treatment was 59 years (range, 42-84). Other notable baseline characteristics included gender (57% male), high risk disease (61%), extramedullary disease (30%), IgG isotype (63%), and prior stem cell transplant (64%). Twenty-eight (42%) patients received full dose VTD PACE. The median prior lines of therapy was five (range, 1-17) with a majority of patients being refractory to carfilzomib (64%) and daratumumab (73%). Of the 67 patients, 26 (39%) were penta-refractory. Patient characteristics can be found in Table 1. Response was evaluated in 56 of the 67 patients; 4 (6%) passed away immediately following VTD PACE, 5 (8%) enrolled in hospice and 2 (3%) were missing follow-up labs. The ORR following cycle one was 55% (31/56) with complete remission achieved in 1 (2%) patient, very good partial response in 12 (21%) and partial response in 18 (32%) patients. Response rates following cycle one are summarized in Table 2. Thirty-six patients (54%) were readmitted following cycle one with febrile neutropenia in 21 patients (58%) being the most common reason for readmission. Among 42 patients who had minimal response or better to VTD PACE, five patients (12%) proceeded to chimeric antigen receptor (CAR) T-cell therapy and seven patients (17%) proceeded to autologous stem cell transplant (ASCT). Among 67 patients treated with VTD PACE, 42 patients (63%) were bridged to subsequent therapy and 25 patients (37%) were transitioned to hospice during or immediately following VTD PACE chemotherapy. The median PFS was 2.2 months (IQR 0.1 - 15.2) and median OS was 5.2 months (IQR 0.1 - 45.2).

Conclusions:

This retrospective cohort study demonstrated that VTD PACE is a feasible treatment option for patients with RRMM, especially those with previous exposure to multiple lines of therapy requiring bridge therapy to other novel agent(s), ASCT or CAR-T. Patient factors, such as performance status, and availability of post-VTD PACE therapies should be considered prior to selecting patients for treatment with VTD PACE based on the high rate patients progressing to hospice shortly after one cycle of treatment.

Kurish:Market Access Transformation: Honoraria. Valent:Alexion, AstraZeneca Rare Disease: Research Funding. Anwer:BMS: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy; Allogene Therapeutics: Research Funding.