Attrition Rates in Multiple Myeloma - A Report from indian Patients at A Tertiary Cancer Center

Abstract Because of its relapsing-remitting nature, patients with multiple myeloma 1,2 require extended therapy with chemotherapy, novel agents, autologous stem cell transplants (ASCT), monoclonal antibodies and/or immune therapies for optimal outcomes. Attrition during treatment can negatively impact long-term outcomes and factors influencing the same may be important clues to achieve optimal patient outcomes. This study aims to examine attrition rates and the factors influencing them.We analysed 244 consecutive newly diagnosed patients of multiple myeloma from January 2017 to December 2017 registered at Tata Memorial Hospital, Mumbai. The patient factors such as age, comorbidities, clinical and laboratory evaluations were recorded along with the lines of therapy (LOTs) received, best response and use of ASCT. Attrition was defined as failure to receive a subsequent line of therapy despite progression of the disease or death from disease according to similar stringent definitions used in similar studies elsewhere. Factors influencing attrition were analyzed using the chi-square test for categorical variables, and either the t-test or logistic regression for continuous variables. An odds ratio greater than 1 and a p-value less than 0.05 were considered as statistically significant. The median age of study cohort was 57.11 years, with 66.4% being male. CRAB (Hypercalcemia, renal dysfunction, anemia, bony lesion) features were noted in most patients with following frequencies: 42 (17.3%) patients with hypercalcemia, 70 (28.9%)-renal dysfunction, 15 (6.2%) of the patients received dialysis,139 (56.9%) patients had anaemia at presentation and 213 (87.2%) patients had bony lesions. R-ISS was available for 199 patients with 19 (9.5%), 128 (64.3%) and 45 (22.6%) of them having R-ISS I, II, and III respectively. 26.2% patients had high-risk cytogenetics (as per the IMWG consensus criteria 2016) at presentation. The most common 1st line therapy given was bortezomib, cyclophosphamide and dexamethasone combination (77.5% of patients). 8.2% of patients had stem cell transplants done & 22.63% patients had received maintenance post first-line therapy. The median progression free survival (PFS) and overall survival (OS) was 3.337 years and 5.043 (Range = 4.143–5.943) years respectively.The median OS in the attrited group was 2.87 years (Range 2.37–3.37 years) while those with attrition to second line therapy showed even poorer median OS of 1.08 years (Range 0.67–1.49 years). The attrition rates for individual lines of therapy were 28.6% for the second LOT, 34.2% for the 3rd LOT, and 45.3% for the subsequent LOTs. The overall attrition rate at the end of follow up was 62.9% (141 patients). Among the factors analysed for attrition, on univariate analysis higher age, ECOG scores of 2 or more, renal dysfunction at presentation, ISS stage 3, and not receiving ASCT showed a significantly higher likelihood of attrition. On multivariate analysis (Overall regression model significant with p < 0.001) only having an ECOG of 2 or higher was significantly associated with higher risk of attrition. Our study shows a high proportion of patients do not receive subsequent lines of therapy in our clinical setting highlighting the importance of first-line treatment including ASCT and maintenance. Most effective therapies should be used in earlier lines so that patients can benefit from all available treatment modalities.