(PA-419) Retrospective Analysis of Newly Diagnosed Multiple Myeloma Patients with Partial or Worse Response to First-line Induction Therapy

Introduction:  A small proportion of newly diagnosed multiple myeloma (NDMM) patients do not respond to initial treatment and show adverse outcomes even in the absence of traditional high-risk factors. This study aimed to examine the clinical characteristics, prognosis and factors affecting survival of patients who did not respond adequately to induction therapy.

Methods:   Between January 2015 and December 2022, a total of 176 patients had been diagnosed MM and initially treated with bortezomib and 52 of them had a partial (PR) or worse response to first-line induction therapy containing bortezomib and were included in the study. Information on demographics, laboratory results, imaging, pathology, response and survival was recorded and analysed retrospectively.

Results:   Fifty two patients with PR or worse (34 male and 18 female) had a median age of 60. The overall response rate (ORR) to induction therapy was 84.6%; PR and worse response rate was 29.6% and primary refractory disease rate was 7.3%. The mean overall survival (OS) from start of therapy was 67.4 months (95% CI: 56.5 – 78.3) and the mean progression-free survival time (PFS) was 27 months (95% CI: 19.5 – 34.6). The mean OS was shorter in patients who progressed under first-line induction therapy (76.1, 76.9, 58.7 and 30.6 months for PR, MR, SD and PD, respectively; p=0.005). The mean OS of patients who achieved worse than PR and ≥PR after lenalidomide containing therapy was 43 months and 79 months, respectively (p=0.012) and the mean PFS was 10 months and 33 months, respectively (p=0.001). Overall and progression-free survival (OS-2 and PFS-2) after autologous stem cell transplantation (ASCT) were also found to be shorter in lenalidomide-refractory patients (p=0.015 and p=0.042, respectively). The presence of secondary extramedullary disease (EMD) and high risk cytogenetic abnormalities were associated with decreased overall survival (p=0.052 and p =0.006, respectively). Age over 65 years and secondary extraosseous EMD were independently associated with mortality (HR: 5.2; 95% CI: 1.7 – 16.4; p=0.004 and HR: 12.4; 95% CI: 3.3 – 46.6; p< 0.001, respectively). Increased complete response rates (p=0.016) and improvement in overall survival were demonstrated in the ASCT group (p=0.007).

Conclusions:   Fifty two patients (29.6% of patients) had ≤ PR and 7.3% of patients had refractory disease under bortezomib based induction therapy. Failure to respond to induction therapy negatively affected survival. ASCT is an effective treatment option in this group.