Treatment of First Relapse of Multiple Myeloma in Australia and New Zealand (ANZ): Treatment Patterns and Outcomes: An ANZ Myeloma and Related Diseases Registry (ANZ MRDR) Analysis

Aim: There remains lack of consensus regarding whether relapsed multiple myeloma should be treated at clinical progression (CP) or biochemical progression (BP), and the ensuing clinical outcome. We described practices in Australia and New Zealand (ANZ) and the outcomes in these cohorts. Method: We conducted a retrospective review of ANZ Myeloma and Related Diseases Registry (ANZ MRDR) patients across 5 sites, that had progressed following first line therapy. Additional information was sought regarding timing of treatment at myeloma relapse (BP or CP) and presence of end organ damage (EOD) at 3-6 months. We determined progression free survival (PFS) and overall survival (OS) in these cohorts using Kaplan Meier methods. Results: Among 258 patients, 52% were treated at BP and 48% at CP. There was no significant difference in age, gender, ECOG, stage (ISS-3) or high-risk cytogenetics at diagnosis between groups. There was no significant difference in time to first progression (CP=20.6 months vs BP=21.7 months) or time between progression and initiation of therapy (CP=1.7 vs. BP=2.1 months). Patients treated at CP had a higher rate of persistent opioid requirement at 6 months (CP=32% vs BP=13.9%, p=0.001) and need for a mobility aid at 6 months (CP=12.7% vs. BP=3.5%, p=0.012), but there was no difference in fracture rates between the groups at 6 months (CP=10.6% vs. BP=10.5%, p=0.99). 68% of patients with renal EOD had no renal response as per IMWG at 3 months. There was a trend toward longer PFS and improved OS from initiation of second line therapy for those treated at BP versus those treated at CP however no statistical significance recognised at this study power (PFS: CP=8.5 months vs. BP=11.2 months, p=0.203, OS: CP=23.5 months vs. BP=33.7 months, p=0.06). Conclusion: Initial disease characteristics, time to first progression and time from progression to initiation of second line therapy did not differ between patients treated at BP versus those treated at CP. Treatment at CP was associated with more persistent EOD measured by requirement for opioids and mobility aids and the majority of those with renal EOD failed to have a renal response. Those treated at BP showed a trend towards improved PFS and OS compared to treatment at CP. This trend may be related to persistent EOD or more aggressive disease biology. The lack of statistical significance likely reflects poor power and warrants further investigation.