219TiP - Randomised controlled study to compare efficacy & safety of KRd versus VRd regimens in newly diagnosed multiple myeloma using weekly schedule of generic carfilzomib

Background

Multiple myeloma is the second most common hematological malignancy in the west. In India, it accounts for 1.1% of all malignancies. Here the epidemiology and treatment outcome is often observed to be different than in the west, mainly due to higher proportion of patients with advanced stage at diagnosis, renal failure and presence of extramedullary disease. This study was designed as to our best understanding there has been no head to head comparison between KRd and VRd in India. We are using generic form of carfilzomib with weekly dosing as current data shows better results with weekly regimen. Results from the ENDURANCE trial using biweekly regimen of carfilzomib could not show 3-year survival benefit with KRd in newly diagnosed myeloma patients despite a better response rate with KRd. However, discontinuation rate was more due to adverse events in the VRd arm. Hence it is suggested that comorbidities and toxicity profiles should guide the choice of therapy. The ARROW trial in relapsed myeloma and the MANHATTAN trial in newly diagnosed myeloma patients, both showed superior survival and response with weekly dosing of carfilzomib than the biweekly regimen with comparable toxicity profile. The aim of first-line therapy is to induce a deep, rapid and sustainable response which directly correlates with longer survival and reduced treatment toxicity. With the above data, we reviewed KRd using generic carfilzomib with weekly scheduling in comparison with VRd in our patient cohort.

Trial design

Key inclusion criteria is newly diagnosed multiple myeloma patients as per the IMWG diagnostic criteria aged ≥ 18 years without coronary artery disease. The coprimary endpoints are response rate, safety profile and imaging plus MRD-response in the induction phase in both arms. Sample size is 446 subjects (223 in each arm) with 80.0% power at a 0.05 significance level to detect a difference of 12% with the response in VRd arm being 65%. With a 10% attrition rate, we aim to accrue 490 patients (245 in each) for the whole study. Enrolled patients will be randomly assigned using simple randomisation method using online random table. Table: 219TiP

Response will be assessed as per IMWG criteria and chemotherapy adverse events will be defined as per CTCAE 5.0. Data will be entered in Microsoft Excel spreadsheet. Categorical variables will be described as frequency and proportion. Continuous variables will be described as mean ± standard deviation or median with inter-quartile range as applicable. Categorical primary outcome will be measured using Chi square test or Fisher exact test or multiple logistic regression analysis.

Clinical trial identification

CTRI/2022/05/042759.

Legal entity responsible for the study

Dr. Jasmine Porwal.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.