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

Parameswaran Hari, Dorothy Romanus, Antonio Palumbo, Katarina Luptakova, Robert M. Rifkin, Linh Mai Tran, Aditya Raju, Eileen Farrelly, Stephen J. Noga, Marlo Blazer, Ajai Chari

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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. 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.

Original languageEnglish
Pages (from-to)152-160
Number of pages9
JournalClinical Lymphoma, Myeloma and Leukemia
Volume18
Issue number2
DOIs
StatePublished - Feb 2018

Keywords

  • DOT
  • Overall survival
  • Progression-free survival
  • RRMM
  • Time to next therapy

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