These are the concluding words — for clinicians — from plasma cell dyscrasia expert, outstanding researcher, and friend @rajshekharucms, who explained to us in detail their current approach to patients with high-risk smoldering myeloma @ManniMD1 Check out the full interview +

.@SWOG S2213 Ph3 RCT Dara-VC Induction Followed by ASCT or Dara-VCD Consolidation & Daratumumab Maintenance in Pts w/ Newly Diagnosed AL Amyloidosis [Activated: 12/1/23] https://t.co/OizUfJCJRK #mmsm #bmtsm

4. IMWG study on retrospective study of denosumab efficacy and safety in patients with eGFR<30: N=118. 28% of patients discontinued denosumab due to hypocalcemia!! 33.8% had G3 and 6.2% had G4 hypocalcemia. ⬇️baseline calcium levels (p<0.001) and higher denosumab dose (120 vs.

3. LimiTec Trial: Prospective study of Tec discontinuation after 6-9 months of therapy in patients achieving >=VGPR (BMBx/MRD assessment not required): n=43 with 4 prior LoT, 95% TCR, 44% penta-refractory, 23% with prior BCMA-DT. Median f/u ~11 months. Failure-Free Probability

2. iMMagine-1 Phase 2 trial of Anito-cel (@DrKrinaPatel): >=3 prior LoT, 86% triple-class refractory, 40% penta-refractory, ~40% with high-risk cytogenetics. >=CR rate~70% (79/117 patients) MRD-neg rate (10^-5) among evaluable patients (n=75): 93% At median follow-up ~1 year,

1. MAJESTEC-3 [Tec-Dara vs DPd/DVd]: 1-3 prior LoT including a PI and lenalidomide; prior anti-CD38 exposure permitted (refractory not allowed). Topline results: PFS HR 0.17(!!) and OS HR 0.46 favoring Tec-Dara, with 3-year PFS 83% in Tec-Dara arm! MRD-neg rate (10^-5; NGS)

Here are the top clinically relevant #ASH25 abstract in Relapsed/Refractory #MultipleMyeloma and Supportive Care that I am looking forward to:

7. SEALAND RCT [Seli-R vs R maintenance post-ASCT, with PFS as primary endpoint]: Negative study, stopped early for futility! Grade >=3 AE 85% in Seli-R vs 45% in R arm My thoughts: In the current landscape, Seli does not belong in earlier treatment lines, especially

6. DeRIVE RCT: Dara-Ixazomib-Dex Induction x 8 cycles (Arm A) vs Dara-Bort-Dex x 3 ➡️Dara-Ixa-Dex x 5 (Arm B), with primary endpoint of post-induction >=VGPR rate after C#8. Topline results: Post-Induction >=VGPR rate 28% (Arm A; DId) vs 56.5% (Arm B; DVd➡️DId); p=0.043.

5. JCOG1911/B-DASH study: Dara-VMP induction ➡️Dara-V vs Dara maintenance for 24 cycles in TI MM: While the induction regimen is not relevant in the US, the pre-maintenance randomization provides important evidence on the role of V in maintenance setting. Overall, negative

4. Unique Trajectory of t(11;14) patients in the context of Quad Induction➡️ASCT ➡️MRD-guided consolidation/maintenance: Significantly lower MRD-negativity rate at all time-points (post-induction MRD-neg rate at 10^-5 only 9% ibn t(11;14)! Significantly longer

3. COBRA Trial [KRd vs VRd RCT in both TI and TE NDMM]: KRd arm: KRd Induction x 12 cycles ➡️KR maintenance x 12 cycles; VRd arm: VRd induction x 8 cycles ➡️Rd maintenance x 16 cycles [Co-primary endpoints: MRD-negative CR at 12 mo. and PFS]. Important to note the hard-wired bias

2. Exceptional outcomes in patients with IMS/IMWG standard-risk disease who achieve sustained MRD-negativity (at 10^-5 at least 12 months apart) in the context of Quad Induction➡️ASCT [88% of these patients were monitored off-therapy after 2 sequential MRD-negative tests]:

1. IFM2021-01 Teclille Trial (Tec-Dara in Newly Diagnosed Transplant-Ineligible MM): n=37 with a median follow-up of ~8 months Among 21 MRD-evaluable patients at 6 months, MRD-negativity at 10^-6: 100% PFS/OS @ 7 months: 100% Grade >=3 infections: 14% (100% received IVIG)

Here are the top clinically relevant #ASH25 abstracts in plasma cell disorders that caught my attention. This thread is for abstracts in the newly diagnosed myeloma space:

We are investigating whether Tec-Dara for fixed duration will improve outcomes in dynamic high risk NDMM. Trial available in Washington, Oregon, Colorado, Utah, Tennessee, Wisconsin, Alabama, New York and Texas (Dallas)

Given the emerging data of MajesTEC-3, here is a table of early BCMA based therapies (combination BCMA (Tec-Dara, Belnrep triplet) and Cilta Cel #ASH25 #mmsm @ASH_hematology Efficacy summary

@JoshuaRichterMD @End_myeloma Remarkable results. This will be preferable to CAR T in early line for most patients, especially if we give as a fixed-duration regimen.

Delighted to welcome CMV guru, the fabulous @michyong2 & CAR-T/BsAb infections guru @GemmaKReynolds to the podcast for our premiere infectious diseases in ICH episode!! 🦠 🧫 We talk all things CMV Available wherever you get your podcasts @NCICancer @PeterMacRes

I learnt a lot recording this @BloodCancerTalk episode on CMV in Hematologic Malignancies with the stellar Infectious Disease team at @PeterMacCC @GemmaKReynolds!