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Myleoma (MM) is characterised by frequent disease relapse with the need to introduce further lines of therapy (LoTs). How often all these theoretical options (Dimopoulos et al, 2021) are actually used in "Real World (RW) settings is considered controversial. In recent studies MM patients were found to have attriction rates (ARs) of up to 57% from LoT-1 to LoT-2. (Yong et al, 2016; Fonseca et al, 2020). We aim to assess ARs inside the Austrian Multiple Myeloma Registry and verify treatment patterns in the RW. Methods:Patients with an index diagnosis made between JAN 2009 and AUG 2021 were eligible. Baseline data and treatment patterns were collected. Attrition was defined as being either deceased, progressive without receiving a further LoT, or being lost to follow up for 5 years or more. Results: 571 pts. (n) were identified, of whom 57.1% were men. Median age at FD was 72 years (SD 12.7 y) with a median follow-up of 50.8 months (SD 44.1 m). 507 patients (88.1%) received the first LOT. In 1st LoT 43.2 % (n 219) received stem cell transplantation (SCT), 39.4% (n 200) received maintenance therapy (55.9 % of transplanted patients). The most common treatment in both transplanted and non-transplanted patients was VRD with 20.5 %. AR was nearly constant across LoT 1 to 4 pending between 19.9-27 %. Summarized ARs across all LoTs without SCT was 36% (n 98) compared to 27.7% in the SCT cohort (n 65). A further LoT was instituted in 37.7-48.6 % of pts. in LoT 1-4. Treatment duration (DoT) decreased with a mean of 12.4months in LoT-1 (SD 15.8) to 4 months (SD 15.4) in LoT-5. The exception is LoT-2 with a DoT of 18.4 months (SD 22.1). The latter may be explained by the short observation window with many patients in the 1st line not yet completed. The depth of remission decreases with each subsequent LoT, as PD is present in 10.5% of patients after 1st LoT compared to 29.7% of patients in LoT-5. The risk of attrition decreases by 32.1% in SCT pts. (CI95% 0.679: 0.47-0.99; p=0.045), and follow-up time becomes significantly longer at 53.8 months versus 47.2 months (p=0.007). Patients defined as being victims of attrition were significantly older at 75 years (SD 10.52months, p=0.003). Both factors influence each other, since patients with SCT were significantly younger (64 years, p=0.003). Frontline regimens with a PI and DEX alone increased the risk of falling into AR by 80% (95%CI 1.802:1.09-2.99; p=0.022) compared to triplet and quadruplet inductions. This might mirror the difference between fixed duration vs continuous therapies. Maintenance (nearly uniformly with LEN) in frontline regimens reduces the risk of attrition by 51.5% (95%CI 0,485:0.33-0.73; p<0.001). Conclusions: Overall, our analyses demonstrated ARs significantly lower that than previously reported (Yong et al, 2016; Fonseca et al, 2020). This indicates that issues like drug access and reimbursement might also play major roles with respect to long term results in MM. Our results confirm a negative impact of doublet 1st treatments vs. more intensive ones. The ...

Based on ISS (n ISS I/ II/ III = 48/ 92/ 46) and SKY92, 186 patients were classed into four risk groups: SKY92 high-risk combined with any ISS stage (13%), SKY92 standard-risk and ISS III (21%), SKY92 standard-risk and ISS II (45%) and SKY92 standard risk and ISS I (21%; Kuiper et al., 2015; Blood, 126: 1996 Blood, 126: -2004. The median PFS of these respective groups was 11, 21, 22 and 25 months and the median OS was 18, 49, 56 and 88 mo (PFS: LR p-value = 5x10 -3 ; OS: LR p-value = 2x10 -4 ). Classifying in R-ISS stages (n R-ISS I/II/III = 12/129/28) demonstrated a median PFS of 13, 20 and 30 months (LR p-value = 5x10 -3 ) and a median OS of 25, 54 and 78 months (LR p-value = 1x10 -3 ). Factors independently associated with OS in the multivariate analysis were SKY92-ISS, R-ISS and del17p, whereas only SKY92-ISS and R-ISS remained independently associated with PFS. Eleven SKY92 high-risk patients were treated with lenalidomide and demonstrated a median OS of 55 months compared to 17 months for thalidomide treated high-risk patients (n = 15). The median OS in standard-risk patients was 59 months (lenalidomide) vs 61 months (thalidomide). Using an interaction term in the Cox regression model, a significant difference in OS (p = 0.04) was found between the treatment arms conditional on SKY92 risk status. Summary/Conclusion: Also in non-transplant eligible MM patients, the SKY92 classifier is a robust marker to identify high-risk patients. The SKY92-ISS has prognostic value independent of the revised ISS. In addition, SKY92 high-risk patients appear to have a survival benefit of lenalidomide treatment over thalidomide treatment, which is not found for SKY92 standard risk patients.

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