(PA-497) Real World Survival Outcomes of Relapsed and Refractory Multiple Myeloma Patients Receiving Second Line Therapy and Beyond in Asia

Multiple myeloma(MM) is the 2nd most common hematological cancer in Asia. Global studies in relapsed/refractory MM(RRMM) lack adequate Asian representation. AMN010, a multi-country, real world retrospective study, aimed to assess treatment patterns and survival of Asian RRMM patients after 1 (2L), 2 (3L) or 3 (4L) prior lines of therapy

Methods:

Patients receiving 2L, 3L or 4L treatment from 25 sites across 6 Asian countries/regions between January 2020 and February 2022 were consented and recruited if they fulfilled IRB approved protocol specific inclusion/exclusion criteria. Primary endpoint was progression-free survival (PFS) analyzed by Kaplan-Meier method; secondary endpoints were overall response rate (ORR), duration of response, time to next treatment or death (TTNTD), prognostic factors and overall survival (OS). Subgroup analyses by age, sex, ECOG, ISS, country and ASCT status were performed. Cox regression was performed to determine prognostic factors and correlation with PFS

Results:

Patients receiving 2L (n = 626), 3L (n = 341) or 4L (n = 156) therapy were analyzed. The most common regimens for 2L, 3L and 4L were carfilzomib/lenalidomide/dexamethasone(KRd); pomalidomide/dexamethasone(Pd); & daratumumab monotherapy, respectively. Overall, median PFS (mPFS) was 16.4 months (mo) (2L), 9.1 mo (3L), 5.3 mo (4L). ORR was 71.6% (2L), 59.2% (3L), 43.6% (4L), with deep responses (sCR/CR) falling from 23.3% (2L) to 5.2% (4L). TTNTD shortened from 26.3 mo (2L) to 15.1 mo (3L). Median OS was not estimable in 2L/3L but was 18.2 mo in 4L. Prior ASCT improved median mPFS (18.7 vs. 14.9 mo) and 24-mo OS (85.9% vs. 75.8%) in 2L. Across lines, longer PFS was observed with ECOG 0, ISS I/II, younger age, and better renal function. IMiD and double class refractory (PI + IMiD) patients in 2L and 3L had mPFS of 5.3-6.6 mo. By the end of the study, 15.5% of 2L, 21.7% of 3L and 51.3% of 4L patients had died.

Focusing on the cohort in China, PFS in 2L, 3L, and 4L were 10.7, 10.3, and 5.7 mo respectively.  ORR was 58.4% vs 59.4% Vs 34% whereas sCR/CR rates were 21.6%, 18.8% and 1.9% across 2L, 3L and 4L groups. Median OS was not evaluable in all groups. Limitations of the study include retrospective nature, heterogenous population and treatment patterns and selection bias.

Conclusions:

In this largest to date RW study from Asia, survival outcomes of RRMM (notwithstanding the differing treatment patterns) are broadly similar to published earlier western data, with declining ORR / CR / PFS and higher attrition with increasing lines of therapy. Quadruplets and monoclonal antibody-based triplets are used less often in front-line and early relapses, in keeping with the regulatory approvals / reimbursements. Whilst further analysis is being planned, survival outcomes highlight the need for earlier adoption of innovative therapies.

We acknowledge and thank patients, research teams, Singapore Clinical Research Institute & International Myeloma Foundation for study support & GSK for funding.