KEY TAKEAWAYS
- The SWOG phase III trial aimed to identify how reducing dexamethasone dosage affects post-induction outcomes in newly diagnosed multiple myeloma patients.
- The result demonstrated that the dexamethasone dose reductions during induction didn’t affect long-term survival in newly diagnosed MM, supporting the potential for dose de-escalation and personalized therapy.
Dexamethasone (Dex) is crucial for initial therapy in newly diagnosed multiple myeloma (NDMM), though often reduced due to side effects like insomnia and anxiety. While 40 mg weekly was established as a standard by the E4A03 trial, clinical practice frequently sees dose reductions, prompting an investigation of its impact.
For a study, researchers aimed to identify how reducing dexamethasone dosage affects post-induction outcomes in newly diagnosed MM patients.
The secondary analysis involved data from two completed studies on newly diagnosed multiple myeloma (NDMM): S0777(comparing VRd vs Rd) and S1211 (comparing Elo-VRd vs VRd). The subset for analysis included patients who completed all eight 3-week induction cycles (or six 4-week cycles in the S0777 Rd arm). DEXfullDose identified patients with no changes to the initial dex dose(either 40 mg once per week or 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of 21-day cycles). At the same time, DEXlowered included those with a lower end-of-induction dex dose and/or frequency than the initial values.
As an exploratory analysis, they compared progression-free survival (PFS) and overall survival (OS) between the DEXfullDose(no changes to dex strength during induction) DEXveryLow (dex dosing reduced ≥50% during induction) subgroups. Landmarking from the end of induction (24 weeks from registration) accounted for the time-dependent nature of dex treatment, and survival curves were generated using the Kaplan-Meier method, with comparisons assessed by the log-rank test.
Of 541 assessable patients (n = 441 from S0777, n = 100 from S1211), 76% (n=410) experienced a reduction in dex during induction. Compared to DEXfullDose patients, those with DEXlowered were more likely to exhibit anemia (37% vs. 26%, P=0.02). However, the two groups had similar distributions in terms of age ≥70 (24% of DEXlowered vs. 26% for DEXfullDose), Performance Status >1 (15% vs. 12%), ISS stage 3 disease condition (33% vs. 27%), ≥60% bone marrow plasma cell burden (37% vs. 31%), M-spike >3 g/dL (48% vs. 48%), platelets <150,000 cells/mm3 (18% vs. 14%), LDH ≥190 U/L (36% vs. 41%), & baseline CRP ≥8 mg/L (27% vs. 30%).
PFS demonstrated no significant difference between DEXlowered (median 36 months, 95% CI 29 to 39 months) & DEXfullDose (median 33 months, 95% CI 24 to 48 months) with P=0.90. Similarly, overall survival (OS) was comparable between DEXlowered (median 77 months, 95% CI 68 months to NR) and DEXfullDose (median 92 months, 95% CI 65 months to NR) with P=0.93. Within the DEXveryLow subgroup (≥50% reduction in dex dosing during induction), the median PFS was 39 months (95% CI 34 to 50 months), the median OS was NR (95% CI NR to NR). and 1E show comparable PFS and OS between these patients and DEXfullDose patients.
The result demonstrated that the dexamethasone dose reductions during induction didn’t affect long-term survival in newly diagnosed MM, supporting the potential for dose de-escalation and personalized therapy.
Source: https://ash.confex.com/ash/2023/webprogram/Paper181744.html
Clinical Trial: https://clinicaltrials.gov/study/NCT00644228
Banerjee R, Sexton R, Cowan AJ, Ailawadhi S, Rajkumar SV, Kumar SK, Lonial S, Barlogie B, Durie BGM, Usmani SZ, Hoering A, Orlowski RZ. Impact of Dexamethasone (Dex) Dose Strength on Outcomes in Newly Diagnosed Multiple Myeloma (NDMM): A Secondary Analysis of SWOG Studies S0777 and S1211. Abstract 1066.ASH Annual Meeting and Exposition 2023.
