P-354: Real-world comparison of progression free survival and time to next therapy endpoints in newly diagnosed patients with multiple myeloma

Introduction: The IMWG 2016 progression criteria are used to determine the progression free survival (PFS), a common clinical trial endpoint. Real-world health administrative databases studies lack the granular biomarker data required to assess disease progression, and therefore often use time to next treatment (TTNT) as a proxy for PFS. However, the timing of next-line treatment initiation can vary based on a patient’s demographic or disease characteristics or treatment tolerability, and this may lead to discrepancies between the PFS and TTNT. Therefore, we aimed to assess how first-line PFS and TTNT compare in real-world patients, and whether these endpoints differed among high cytogenetic risk, transplant eligible, or transplant ineligible patients with newly diagnosed MM (NDMM).

Methods: This single-center Canadian retrospective cohort study included patients diagnosed with MM after January 2015 treated with standard of care novel agent regimens in a non-clinical trial setting. PFS was defined as the time between first line treatment initiation and disease progression (as per the IMWG 2016 criteria) or death, and patients were censored if treatment was changed reasons other than progression. TTNT was defined as the time between first line treatment and initiation of next line therapy for any reason or death. High risk cytogenetics was defined as the presence of del(17p), t(4;14), t(14;16) or amplification 1q. Time to event analysis was conducted using the Kaplan Meier method.

Results: A total of 483 NDMM patients were included in this study. The median age at diagnosis was 69.1 (interquartile range 62.2-76) years, 83 (17%) patients had high risk cytogenetics at diagnosis, and 242 (49%) patients underwent an upfront autologous transplant. During study follow up, 198 (41%) patients met IMWG progression criteria, 9 (5%) of whom did not receive second line treatment (n=1 was lost to follow up, n=8 were palliated). Overall, 27 (6%) patients transitioned to second line treatment without meeting IMWG progression criteria (n=11 due to toxicity on first line therapy, n=10 to deepen disease response, and n=6 for unknown reasons). In the overall cohort, the median PFS was 40.1 (95% CI 34.8-47.3) months whereas the median TTNT was 39.2 (95% CI 34.8-43.8) months (p =0.573). There was no significant different in the median PFS or TTNT among patients with baseline high risk cytogenetics (mPFS 27.8 [95% CI 16.7-49] months vs mTTNT 23.8 [95% CI 15-38.3] months, p=0.545), transplant eligible patients (mPFS 61.9 [95% CI 49-80] months vs mTTNT 64 [95% CI 54.6-76.3] months, p=0.874), or transplant ineligible patients (mPFS 26 [95% CI 20.9-30.1] months vs mTTNT 23.9 [95% CI 20.2-28.5] months, p=0.456).

Conclusions: This was the first study to compare the PFS and TTNT of real-world NDMM patients treated with novel agents. We showed that PFS and TTNT were comparable endpoints, which supports the use of TTNT as a surrogate measure of PFS in real-world studies.