Characteristics and Outcomes of Non-Transplanted Patients with Newly Diagnosed Multiple Myeloma (NDMM) Initiating Treatment with Bortezomib, Lenalidomide, and Dexamethasone (VRd) As First-Line of Therapy
Authors: Medhekar Rohan , Ran Tao , Fu Alex Z. , Patel Sharmila , Kaila Shuchita 
Published: November 2021

Abstract
Introduction: In the US, bortezomib, lenalidomide, and dexamethasone (VRd) is one of the preferred treatment regimens in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) based on the results from the phase 3 Southwest Oncology Group (SWOG) S0777 study. Although the efficacy of VRd in transplant-ineligible or -deferred NDMM patients was demonstrated in SWOG S0777, clinical trials have strict eligibility criteria that may not translate to the real-world. There is limited real-world data on the characteristics and outcomes of non-transplanted patients with NDMM treated with VRd, especially in older, frail patients with comorbidities. This study aimed to address these knowledge gaps by evaluating the characteristics and outcomes of patients with NDMM who received VRd as first-line of therapy (LOT) in US oncology practice.
Methods: This retrospective observational study included patients from the Flatiron Multiple Myeloma Core Registry who received VRd as first LOT between November 1, 2015 and February 28, 2021. The index date was defined as the first observed record of the VRd regimen. Non-transplanted patients were defined as those who did not receive a stem cell transplant (SCT) from the diagnosis date to the index date. Patients were excluded if they were &lt;18 years of age on index date; were enrolled in a clinical trial; had other malignancies prior to the index date; had a diagnosis of amyloid light-chain amyloidosis prior to the index date; or had a SCT prior to index date. Demographics, clinical characteristics, and outcomes were assessed in the overall study cohort and among specific subgroups: older adults (≥75 years of age on index date); frail patients (frailty score ≥2, calculated using age on index date, Charlson Comorbidity Index during the pre-index period, and Eastern Cooperative Oncology Group performance status [ECOG PS] score on the closest date to the index date ≤90 days prior to and ≤7 days after the index date, patients with missing ECOG were not excluded); patients with high-risk cytogenetics, and patients with acute renal impairment ([RI], serum creatinine &gt;2 mg/dL on the closest date to the index date or having diagnosis codes of ICD-9-CM 584.5-584.9, ICD-9-CM 586, ICD-10-CM N17.0-2, N17.8-9, and N19, measured ≤90 days prior to and ≤7 days after the index date). Duration of therapy was measured as the time between the index date and end of the LOT. Progression-free survival (PFS) was measured as time between the index date and disease progression or death, whichever occurred first. PFS did not account for treatment discontinuation for reasons other than progression or death. Disease progression was defined as a clinically meaningful increase in serum M-protein, urine M-protein, or the free light chain ratio according to the International Myeloma Working Group criteria. PFS was analyzed using the Kaplan-Meier method.
Results: A total of 2342 eligible NDMM patients treated with VRd as first LOT were identified, with a median follow-up of 21.0 months. A majority of patients were ≥65 years (64.3%), with the mean (SD) age at index date being 67 (±10) years. Most patients were male (53.3%), had International Staging System [ISS] stage I/II (48.4%; 33% missing) and the ECOG PS score 0/1 (63.5%; 22% missing). Of the 2342 patients, 597 (25.5%) patients were categorized as older adults (≥75 years of age); 1122 (47.9%) as frail; 374 (16.0%) as patients with high-risk cytogenetics; and 250 (10.7%) as patients with RI. About 28% of the patients received a SCT within 1-year of the index date. The median duration of therapy was 5.6 months. The median PFS for the overall study group was 33.2 months. Median PFS was substantially shorter for patients who were ≥75 years of age (22.8 months), were frail (28.7 months), had high-risk cytogenetics (25.1 months), or had RI (25.1 months) (Figure).
Conclusions: The majority of patients with NDMM treated with VRd in the real-world setting were aged ≥65 years, were ISS stage I or II, had an ECOG PS score of 0 or 1, and had standard-risk cytogenetics. Median PFS observed in the real-world setting was shorter than that observed in the SWOG S0777 clinical trial. Patients who were ≥75 years of age, were frail, had high-risk cytogenetics, or had RI demonstrated shorter median PFS than patients in the overall study population. Alternate treatment options with demonstrated efficacy in the older, frail, and transplant ineligible patients are available.
Figure 1 Figure 1.

Disclosures
Medhekar: Janssen: Current Employment. Ran: Janssen Scientific Affairs, LLC: Current Employment. Fu: Janssen: Current Employment. Patel: Janssen: Current Employment. Kaila: Janssen Scientific Affairs, LLC: Current Employment.

OffLabel Disclosure:
Bortezomib, and lenalidomide are both FDA approved agents for treating multiple myeloma. The combination of bortezomib, lenalidomide, and dexamethasone is commonly used in clinical practice and is listed as a preferred regimen in NCCN guidelines.