Outcomes with Early Response to First Line Treatment in Patients with Newly Diagnosed Multiple Myeloma

Introduction

One of the most important prognostic factor associated with improved survival in patients with newly diagnosed multiple myeloma (NDMM) is quality of response to first line treatment, especially attainment of complete response (CR) or very good partial response (VGPR). Studies prior to routine use of novel agents had suggested an inferior outcome associated with very rapid response. We designed the current study to evaluate the prognostic impact to the kinetics of response in newly diagnosed myeloma.

Methods

Data from 2,707 consecutive patients with NDMM seen at Mayo Clinic, within 90 days of diagnosis, between 2004 and 2015, was analyzed retrospectively. Of these, 381 (14.1%) patients were lost to follow-up. The data for response assessment was available for 1,086 patients after 2 cycles, 1,207 patients after 4 cycles and 1,636 patients overall. The progression free survival (PFS) was calculated from the date of start of first line therapy till progression or death from any cause or the date of last follow up. The overall survival (OS) was calculated from the date of start of first line therapy till death from any cause or the date of last follow up. The survival curves were generated using Kaplan-Meier method and their differences were estimated using log rank test.

Results

Patients with ≥ VGPR [292 (26.9%) after 2 cycles, 497 (41.2%) after 4 cycles and 983 (60%) overall best response] were compared with those who achieved < VGPR [794 (73.1%) after 2 cycles, 710 (58.8%) after 4 cycles and 653 (40%) overall best response].

The comparison of the patients with ≥ VGPR and < VGPR after 2 cycles is provided in Table 1, along with baseline characteristics and details of first line treatment. Overall, early responders (≥ VGPR by 2 cycles) appear to have higher rate of light chain only disease and high risk cytogenetics, especially t(4;14).

The median follow-up for the entire cohort was 68.2 months (95% CI; 65.3, 70.7) from the start of first line treatment. The PFS as well as OS were not significantly different among patients who achieved ≥ VGPR and < VGPR after 2 cycles (Figure 1A and 2A, respectively) and after 4 cycles (Figure 1B and 2B, respectively), though both are significantly improved among those who achieved VGPR or better as the overall best response to first line treatment (Figure 1C and 2C, respectively).

Conclusion

The quality of response with attainment of CR / VGPR and the kinetics of response with increasing depth of response over time is an important favorable prognostic factor for survival in patients with NDMM. Patients with high risk disease appear to achieve early response (≥ VGPR by 2 cycles). A rapid achievement of a deep response does not affect long term outcomes.

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