General MM

Impact of abnormal pulmonary function on outcomes in patients with newly diagnosed multiple myeloma

The improvements in novel therapeutic approaches have significantly improved the survival rates of patients with multiple myeloma (MM) in recent years.1 However, the presence of pre-existing pulmonary disease may affect treatment availability and survival in patients with MM; with retrospective studies demonstrating patients with MM and lung disease have worse outcomes.2

Associate Professor Georgia Trakada from the National and Kapodistrian University of Athens, Athens, GR, and colleagues, published findings from a prospective non-interventional trial examining the prognostic value of pulmonary function tests (PFTs) in patients with newly diagnosed, symptomatic MM.3 At the time of diagnosis, prior to anti-MM therapy, the lung function of consecutive enrolled patients (n = 121; median age = 67 years; range, 37–90) was evaluated using PFTs. The aim of the study was to assess the association of lung function and outcome over time.

Key findings:

  • Median follow-up: 32 months
  • Median hemoglobin levels: 10.4 g/dl
  • Primary treatments:
    • Bortezomib-based therapy: 69%
    • Lenalidomide-based therapy: 31%
    • High-dose melphalan with autologous stem cell transplantation at first-remission: 35%
  • Assessment of pulmonary function:
    • Normal PFTs outcomes: 49.6% (n = 60)
    • Restricted breathing patterns following PFTs analysis: 23.9% (n = 29)
    • Obstructive breathing pattern following PFT analysis: 18.2% (n = 22)
    • Mixed results following PFT analysis: 2.5% (n = 3)
  • Three-year progression-free survival (PFS) in all patients: 47%
  • Three-year overall survival (OS) in all patients: 64%
  • Patients with an obstructive breathing pattern had significantly worse median OS compared to other patient groups: 32.8 months (obstructive pattern) vs 5 months (restrictive pattern) vs not reached (normal pattern), P = 0.013
  • Death within the first year from the start of therapy was associated with an obstructive pattern: HR = 8 (95% CI, 2.1–30), P < 0.001
  • A clinical predictor for survival included a peak expiratory flow (PEF) rate of < 65% versus ≥ 65%: 33 months vs not reached at three years (HR = 2.8; 95% CI, 1.47–5.5; P = 0.001)
  • Median OS differed based on carbon monoxide diffusion capacity (DLCO) rate, with < 65% versus ≥ 65%: 33 months vs not reached (HR = 2.54; 95% CI, 1.3–5.1; P = 0.005)
  • Independent prognostic factors for OS included: PEF < 65% and/or DLCO < 65%
    • For patients with none or one of these prognostic factors, median survival was not reached
    • For patients with both prognostic factors, median survival was 7 months

The authors concluded that the results from this first prospective analysis on the prognostic value of pulmonary function assessment in patients with MM demonstrated lung dysfunction independently affects the outcomes of patients with MM. Moreover, the integration of pulmonary function analysis at diagnosis, with consideration of results in the treatment pathway of patients with MM, may allow for further improvements to survival and reduce treatment-related complications.

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. [Epub 2013 Oct 25]
  2. Kleber M. et al. Validation of the Freiburg Comorbidity Index in 466 multiple myeloma patients and combination with the international staging system are highly predictive for outcome. Clin Lymphoma Myeloma Leuk. 2013 Oct; 13(5): 541–551. DOI: 10.1016/j.clml.2013.03.013. [Epub 2013 Jun 27]
  3. Trakada G. et al. Pulmonary function abnormalities are common in patients with multiple myeloma and are independently associated with worse outcome. Ann Hematol. 2019 Mar 5. DOI: 10.1007/s00277-019-03641-x.
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