Dorothy Romanus

Prolonged Duration of Therapy Is Associated With Improved Survival in Patients Treated for Relapsed/Refractory Multiple Myeloma in Routine Clinical Care in the United States

Background In clinical trials, an extended therapy duration has been associated with better outcomes in patients with newly diagnosed multiple myeloma (NDMM). However, data on how the therapy duration affects the outcomes for patients with relapsed/refractory multiple myeloma (RRMM) are limited. We conducted a large, retrospective study in the United States to evaluate the effect of the duration of second‐line therapy on overall survival. Patients and Methods Adults with NDMM from January 2008 to June 2015 were followed up to identify their second‐line therapy. The duration of therapy (DOT) and time to next therapy (TTNT), as a proxy for progression‐free survival, were estimated using the Kaplan‐Meier method. The relationship between the duration of second‐line therapy and overall survival was evaluated with a logistic marginal structural model to mitigate the risk of treatment selection and survival bias. Results A total of 628 NDMM patients developed a relapse after initial therapy. The median DOT for second‐line therapy was 6.9 months (95% confidence interval [CI], 5.9‐7.7 months), which was shorter than the corresponding TTNT (median, 15.1 months; 95% CI, 13.4‐17.3 months). Each additional month of second‐line therapy was associated with a reduced adjusted risk of death at 1 year (odds ratio, 0.78; 95% CI, 0.77‐0.83; P < .001). Conclusion In a large database capturing a heterogeneous patient population and varied treatment patterns reflecting routine clinical care, we found a clinical benefit for continued longer DOT at first relapse. Despite the emerging paradigm favoring continuous therapy, second‐line progression‐free survival (utilizing TTNT as the proxy) was more than twofold longer than the DOT. Understanding the barriers to extended DOT could help to improve the outcomes for RRMM patients. Micro‐Abstract Despite the emerging paradigm favoring continuous therapy, we found that in routine clinical care, myeloma patients at first relapse frequently discontinue treatment before progression, resulting in a therapy duration that is significantly shorter than the interval to the next therapy. We further describe the association between the length of second‐line therapy and improved overall survival for patients with relapsed/refractory multiple myeloma.

Factors associated with second-line triplet therapy in routine care in relapsed/refractory multiple myeloma

Second‐line therapy (SLT) trials in relapsed/refractory multiple myeloma (RRMM) report superior outcomes with triplet combinations. We sought to determine factors associated with triplet SLT in routine practice.

The impact of age and comorbidities on practice patterns and outcomes in patients with relapsed/refractory multiple myeloma in the era of novel therapies

OBJECTIVES One-third of patients with multiple myeloma (MM) are diagnosed at age≥75years. Older patients have increased incidence of cardiovascular disease (CVD) and renal insufficiency (RI), hallmark complications of MM. We examined cumulative incidence of CVD and RI in relapsed/refractory MM (RRMM) and outcomes by age and RI/CVD. MATERIALS AND METHODS Retrospective cohort study using a large US electronic medical records database of adult patients with RRMM initiating first- and second-line therapy (2LT) between 1/2008-06/2015. RI and CVD comorbidities were based on diagnosis codes and/or lab values. RESULTS Among 628 patients, 37.1% were ≥75years. Cumulative incidence of CVD and/or RI increased from 47.7% at MM diagnosis to 67.8% at first relapse. Age≥75years had a trend toward higher risk of relapse post 2LT, proxied by time to next treatment (TTNT), (adjusted HR: 1.28; 95% CI: 1.00, 1.65; P=0.05). TTNT was significantly higher with comorbid CVD+RI (adjusted HR: 1.50; 95% CI: 1.11, 2.02; P<0.01). Age≥75years, RI, CVD, and CVD+RI were associated with increased mortality risk from 2LT initiation; adjusted HR: 1.66 (95% CI: 1.19, 2.33; P<0.01), 1.51 (95% CI: 1.01, 2.26; P=0.04), 1.75 (95% CI: 1.03, 2.96; P=0.04), and 1.95 (95% CI: 1.29, 2.93; P<0.01), respectively. CONCLUSION Despite treatment with novel agents for RRMM in 86% of patients, an outcome gap persists for older patients and those with RI and/or CVD. Personalized treatment approaches that account for age and comorbidities, and further evaluation of innovative regimens and dosing schedules, are needed to improve outcomes for these patients.