PB2121 POST‐TREATMENT IMMUNE RECONSTITUTION IN MYELOMA IS ASSOCIATED WITH IMPROVED PROGRESSION FREE SURVIVAL IN THE ERA OF NOVEL THERAPY; A RETROSPECTIVE ANALYSIS IN AN AUSTRALIAN HAEMATOLOGY DEPARTMENT
Authors: Agrawal S. , Presgrave P. , Warburton P. , Cartwright K. , Desai S. , King K. , Parmar G. 
Published: June 2019

Background:

Immunoparesis in myeloma has been defined as suppressed levels of uninvolved polyclonal immunoglobulin (Ig). The association between immunoparesis at diagnosis and an unfavourable prognosis has been inconsistently reported. This discrepancy might be due to population factors, treatment factors or even due to immune reconstitution during treatment. Polyclonal Ig recovery post autograft has been associated with increased progression free survival (PFS) but these reports largely analyse populations from the pre‐novel therapy era. The influence of immune recovery on survival in the era of novel agents such as proteasome inhibitors and immunomodulatory imide drugs (IMiDs) is not well documented.

Aims:

The primary goal of this study was to assess whether recovery of uninvolved polyclonal Ig after first line treatment with novel therapy was associated with improved survival. We also aimed to assess the disease and treatment characteristics that may influence Ig recovery.

Methods

A retrospective analysis of newly diagnosed symptomatic myeloma patients who presented with immunoparesis and were treated upfront with novel agents at Wollongong Hospital between the years 2011 and 2016 was performed. A total of 48 patients were identified who met these criteria. Analysis was performed in December 2018 allowing for a minimum two year follow up period after diagnosis. Survival curves were constructed according to the Kaplan‐Meier method. A p‐value of < 0.05 was considered significant. All statiscal analyses was perfomed using GraphPad Prism version 7 software.

Results:

The median age of our population was 64 years (see attached table for more detailed patient characteristics). Of these patients, 6/48 (12.5%) had complete recovery of their uninvolved polyclonal Ig measured at a mean of 16 months post initiation of therapy. All six patients had an IgG paraprotein, and all six received up‐front autograft. 5 of 6 patients received Bortezomib based therapy whilst one received Thalidomide. The remaining 42 of 48 patients (88%) had incomplete or no recovery of their uninvolved polyclonal Ig at a mean of 14 months post therapy initiation. Only 60% (25/42) of this group had an IgG paraprotein and 67% (28/42) received an autograft up‐front. 64% (27/42) received Bortezomib whilst 29% (12/42) received IMiD therapy. There was a significantly (p = 0.0449) longer PFS seen in the group who had complete Ig recovery (49 months) when compared with the group with incomplete Ig recovery (28.5 months). There was also a trend towards enhanced overall survival (OS) in the complete Ig recovery group (68.7 months) compared with the incompletely recovered group (47.9 months) but statistical significance could not be shown (p = 0.075). The rates of infective episodes within the first six months of treatment were similar in the recovered (1.3 episodes) and incompletely recovered (1.1 episodes) groups. On further analysis of the incompletely recovered group, there was no significant difference in OS or PFS when comparing those with recovery of one uninvolved Ig subtype (10/42 patients) with those who had no Ig recovery (32/42 patients).

Summary/Conclusion:

Early complete recovery of polyclonal uninvolved immunoglobulin in myeloma patients treated with novel agents is associated with longer PFS with a trend towards increased OS also noted. A reduced incidence of early infections was not seen in those who had early immune recovery suggesting other mechanisms are likely to account for the increase in survival. Further comparison including multivariate analysis will be presented in the meeting.

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