General MM,   Relapsed/refractory patients

Clinical characteristics and the pattern of progression are important prognostic factors for post-progression survival in multiple myeloma

Multiple relapses requiring several lines of therapy characterizes multiple myeloma (MM), with the durability of remissions improved over recent years by the development of novel agents such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (MoAbs).1 The International Myeloma Working Group (IMWG) categorizes disease relapse into progressive disease, an increase in measurable monoclonal protein by 25%, and clinical relapse, new end-organ dysfunction.2,3 Rajshekhar Chakraborty from the Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA, and colleagues, conducted a retrospective cohort study which aimed to evaluate survival following clinical progression (CP), with and without extramedullary (EM+/EM-), as a measure of biochemical progression (BP) in patients with MM.4 

All consecutive newly diagnosed MM patients (n = 527) treated at the Cleveland Clinic between 1 January 2008 and 31 December 2015 were analyzed for treatment course and progression pattern, with follow-up for relapse continuing until 28 February 2018. Throughout this time period, induction, maintenance, and subsequent therapies routinely consisted of PIs and IMiDs.

Key findings

All data are shown as BP vs CR/EM- vs CR/EM+, where applicable

  • Patients experiencing first relapse by February 2018 and requiring further therapy, n = 252
  • Median age at first relapse: 64 years (range, 27–87)
  • Median time from diagnosis to first relapse: 24 months (range, 2–84)
  • No significant difference in relapse patterns in patients who received PIs and/or IMiDs vs traditional cytotoxic agents as first-line therapy
  • At time of disease progression, 134 patients (53%) had BP and 118 patients (47%) presented with CP, of which 35% had CP/EM- and 12% had CP/EM+ 
  • High-risk cytogenetics at diagnosis were found in a greater proportion of patients presenting with CP/EM+ compared to CP/EM- or BP: 45% vs 35% vs 22%, P = 0.09, respectively
  • Median time from diagnosis to first relapse was shorter in patients presenting with CP/EM+ compared to CP/EM- or BP, respectively: 13 months vs 25 months vs 25 months, P = 0.003
  • Median follow-up of patients: 27 months vs 23 months vs 32 months
  • Median overall survival: 49.5 months vs 19.2 months vs 10.2 months, P < 0.001
  • Median progression-free survival: 16.7 months vs 6.3 months vs 5.1 months, P < 0.001

In conclusion, this retrospective analysis illustrates that clinical characteristics and the pattern of progression are important prognostic factors in post-progression survival for MM patients. The authors added that these findings highlight the importance of reporting the pattern of progression for relapsed MM patients at entry into clinical trials. To validate the prognostic significance of the pattern of progression, prospective trials are needed.

References
  1. Kumar S.K. et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014 May; 28(5): 1122–1128. DOI: 10.1038/leu.2013.313.
  2. Kumar S. et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016 Aug; 17(8): 328–346. DOI: 10.1016/S1470-2045(16)30206-6.
  3. Laubach J. et al. Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group. Leukemia. 2016 May; 30(5): 1005–1017. DOI: 10.1038/leu.2015.356.
  4. Chakraborty R. et al. Progression with clinical features is associated with worse subsequent survival in multiple myeloma. Am J Hematol. 2019 Jan 21. DOI: 10.1002/ajh.25415. [Epub ahead of print]
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