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Tec-dara or tec alone at first relapse? In Europe that's now a real choice,. The EC just extended teclistamab monotherapy to RRMM after at least one prior therapy, based on MajesTEC-9. That comes about two months after tec-dara got its 2L approval off MajesTEC-3. Reminder on the trial: tec vs PVd or Kd in 1-3 prior lines, all pts len and anti-CD38 exposed. We saw the results fo this by Dr Mina and colleagues at ASCO. - PFS HR 0.29, OS HR 0.60. 18-mo PFS 69.8% vs 26.9%. An OS benefit at first relapse against a PI-based control is not something we see often - ≥CR 65.9% vs 16.8%. That depth in a len- and dara-exposed population is what changes the convesation in clinic - The new label moves to monthly dosing from month 7, and as early as month 3 for eligible pts. For a drug given until progression, that matters more than people think. Fewer chair visits, maybe fewer infections, though that still needs to be shown - The cost: grade 3/4 infections 41.6% vs 29.0%, grade 5 AEs 6.5% vs 3.5%. Median time on tec was 13.1 vs 7.0 mo, so some of that is exposure, but probaly not all of it The operational piece is infection prevention. IgG checks, IVIG thresholds, antiviral and PJP ppx, and someone who actually owns that for years of therapy. In a 2L population that is fitter and expected to live longer, an infection death costs more. Then sequencing. Use BCMA at first relapse and you are shaping what CAR-T can do later. Cilta-cel after a BCMA bispecific is not the same drug as cilta-cel in a BCMA-naive pt. #MultipleMyeloma #mmsm #Bispecifics

MajesTEC-9 phase 3 trial evaluates teclistamab monotherapy vs investigator’s choice of PVd or Kd in relapsed/refractory multiple myeloma, aiming to redefine treatment standards in RRMM. #mmsm #ASCO26 Congratulations to @RobertoMinaMD et all, patients and their families - 74% https://t.co/Aoost9RjSo

MajesTEC-9 just landed in NEJM, and it's worth more than the headline. Teclistamab — a BCMA bispecific — was tested as a SINGLE agent at first-or-later relapse, in myeloma already exposed to anti-CD38 + lenalidomide, against investigator's choice of PVd or Kd. The topline is a

The proliferative, MYC-driven clones were the ones that cleared best with quad induction. Not what I would have guessed. Nature Medicine, the Nantes/Toulouse IFM group: 423 tumor samples from the MIDAS cohort, all treated with Isa-KRd induction, with genomics, transcriptomics and DNA methylation profiled on the same pts and tied to post-induction MRD. - Expression subtype mattered. HP1/HP3 and MS did better on MRD, MF and CD2 did worse - Proliferation and MYC programs tracked with MRD negativity, B-cell differentiation with MRD positivity. Validated in CASSIOPEIA, which makes me take it more seriously - An integrated random forest model predicted MRD with an AUC of 0.77, beating clinical and genomic models - New driver alterations held up across 1,451 external cases (MMRF, MANHATTAN, CASSIOPEIA) Right now nearly everyone gets the same quad, and we find out months later who responded. A baseline signature that flags the pt unlikely to reach MRD-neg would let us think about escalation before induction is over, not after. In a trial, that could mean adding a T-cell engager early for the predicted MRD-positive group rather than waiting for a positive marrow at the end of induction. Post-induction MRD is an early read, not the finish line. WGS plus RNA-seq plus methylation at diagnosis is not something most centers can order today. Still, this is the kind of biology that should eventualy decide who gets what up front. Great work by Magrangeas, Moreau, Touzeau, Avet-Loiseau, Minvielle, Letouzé and colleagues. #mmsm #Myeloma #MRD

Isa-Iber for maintenance in MRD+ pts in MIDAS trial. Early thoughts - for MRD+ after esp after quad and Tx need novel options - 40% of pts were 11:14; again role of BCL2 targeting - inhibition or degradation Congratulations to team. https://t.co/fDeWaFezdZ

There's a real cluster of MRD-driven trial design in this year's program — PERSEUS at 6+ years, MIDAS testing MRD-adapted maintenance, GEM2014MAIN's long-term data on stopping therapy after sustained MRD-negativity. The question isn't "do quadruplets work" anymore. It's how deep and how long you actually have to treat before it's safe to stop; 🛑; a question not just for T-cell engagers. looking forward to the debate ! #Myeloma #MRD #IMS26

Heading to #IMS26 ! Going through all the amazing abstracts, A few things on my radar this year so far: — CERVINO: first phase 3 readout for a BCMA bispecific vs standard-of-care in triple-class exposed RRMM — PERSEUS at 6+ years — does the PFS advantage for quad induction hold up long-term, and is there finally an OS signal? — Two separate first-in-human reports of in vivo CAR-T generation — no apheresis, no lymphodepletion. If this works, it changes how we think about access to cellular therapy entirely. — CARTITUDE-2 5-year data on cilta-cel in earlier-line RRMM — EXCALIBER-RRMM: iberdomide's first phase President of IMS - Prof Phillip Moreau and his executive team, @myelomaMD @mvmateos @NoopurRajeMD @NikhilMunshiMD have put together an amazing meeting with 669 abstracts and many amazing talks ! I will be tweeting important practice changing abstract through rest of week; excited for busy week :) #Myeloma #HemOnc #IMS2026 #glasgow

There's a real cluster of MRD-driven trial design in this year's program — PERSEUS at 6+ years, MIDAS testing MRD-adapted maintenance, GEM2014MAIN's long-term data on stopping therapy after sustained MRD-negativity. The question isn't "do quadruplets work" anymore. It's how deep and how long you actually have to treat before it's safe to stop; 🛑; a question not just for T-cell engagers. looking forward to the debate ! #Myeloma #MRD #IMS26

New IMS/IMWG NGS-based risk criteria from the PERSEUS study showed daratumumab benefit across both high- and standard-risk multiple myeloma patients, supporting broader efficacy regardless of risk status. #mmsm #ASCO26 This is a great reassurance to see DaraVRD combo continues https://t.co/pj0VnUS0sG

One shot a month, one step-up dose, dex only in the first 2 cycles. And no transplant planned. That's Arm G of MajesTEC-5 (GMMG-HD10/DSMM-XX), the first data for a trispecific in NDMM, oral at #ASH26 (abstract 110). Ramantamig hits BCMA and GPRC5D through CD3, given with dara-len for 6 cycles, then ram-dara maintenance in place of ASCT. Quick thoughts - 21 TE-NDMM pts, median age 61. ORR 100%, ≥CR 81%, and all 20 MRD-evaluable pts were MRD-neg (10^-5, NGF) after just 3 cycles - CRS in 17/18 who didn't get prophylactic toci, all grade 1-2. None in the 3 who did. No ICANS, no ataxia - The GPRC5D tax is still there but mild: taste changes 16/21, oral AEs 16/21, none above gr 2. 10 pts lost 5-20% of body weight - Only 3 gr 3 infections, nothing gr 4+. But 15/21 had an IgG <400 and 18/21 got IgG replacement - Stem cell collection after C3 worked, median 5.6 x10^6/kg in 19 pts Dual antigen targeting upfront is the most direct shot we have at antigen escape, and a Q4W schedule with almost no steroid is something community sites could actualy run. 21 pts, 7.1 mo median f/u, only 3 high-risk by IMS-IMWG. MRD-neg at 10^-5 is near the ceiling for every quad-plus-immunotherapy arm now, so it can't seperate regimens anymore. What matters is durability without ASCT, and only the maintenance readout tells us that. There's a practical cost too. IVIG in nearly every pt, for who knows how long, is chair time and money we tend to wave off in early phase data. Nice work by Marc Raab, Leo Rasche, Hermann Einsele and the GMMG/DSMM team. Exciting days ahead for all. #mmsm #MultipleMyeloma #ASH26

Talquetamab in newly diagnosed myeloma, before transplant. MajesTEC-5 (GMMG/DSMM) at #IMS26, 20 patients on Tal-Dara-Len induction: 90% MRD-negative before maintenance. 20% stopped talquetamab because of side effects. https://t.co/FpnDqIfD2q

Tec-dara or tec alone at first relapse? In Europe that's now a real choice,. The EC just extended teclistamab monotherapy to RRMM after at least one prior therapy, based on MajesTEC-9. That comes about two months after tec-dara got its 2L approval off MajesTEC-3. Reminder on the trial: tec vs PVd or Kd in 1-3 prior lines, all pts len and anti-CD38 exposed. We saw the results fo this by Dr Mina and colleagues at ASCO. - PFS HR 0.29, OS HR 0.60. 18-mo PFS 69.8% vs 26.9%. An OS benefit at first relapse against a PI-based control is not something we see often - ≥CR 65.9% vs 16.8%. That depth in a len- and dara-exposed population is what changes the convesation in clinic - The new label moves to monthly dosing from month 7, and as early as month 3 for eligible pts. For a drug given until progression, that matters more than people think. Fewer chair visits, maybe fewer infections, though that still needs to be shown - The cost: grade 3/4 infections 41.6% vs 29.0%, grade 5 AEs 6.5% vs 3.5%. Median time on tec was 13.1 vs 7.0 mo, so some of that is exposure, but probaly not all of it The operational piece is infection prevention. IgG checks, IVIG thresholds, antiviral and PJP ppx, and someone who actually owns that for years of therapy. In a 2L population that is fitter and expected to live longer, an infection death costs more. Then sequencing. Use BCMA at first relapse and you are shaping what CAR-T can do later. Cilta-cel after a BCMA bispecific is not the same drug as cilta-cel in a BCMA-naive pt. #MultipleMyeloma #mmsm #Bispecifics

One framing point: don't line MajesTEC-9 up against MajesTEC-3. Different experiment — monotherapy vs a tec+DARA doublet, CD38-exposed vs CD38-refractory-EXCLUDED, 17 vs 34 mo follow-up. The matched comparator is MonumenTAL-6 (talquetamab, same CD38-exposed population, PVd arm).

The proliferative, MYC-driven clones were the ones that cleared best with quad induction. Not what I would have guessed. Nature Medicine, the Nantes/Toulouse IFM group: 423 tumor samples from the MIDAS cohort, all treated with Isa-KRd induction, with genomics, transcriptomics and DNA methylation profiled on the same pts and tied to post-induction MRD. - Expression subtype mattered. HP1/HP3 and MS did better on MRD, MF and CD2 did worse - Proliferation and MYC programs tracked with MRD negativity, B-cell differentiation with MRD positivity. Validated in CASSIOPEIA, which makes me take it more seriously - An integrated random forest model predicted MRD with an AUC of 0.77, beating clinical and genomic models - New driver alterations held up across 1,451 external cases (MMRF, MANHATTAN, CASSIOPEIA) Right now nearly everyone gets the same quad, and we find out months later who responded. A baseline signature that flags the pt unlikely to reach MRD-neg would let us think about escalation before induction is over, not after. In a trial, that could mean adding a T-cell engager early for the predicted MRD-positive group rather than waiting for a positive marrow at the end of induction. Post-induction MRD is an early read, not the finish line. WGS plus RNA-seq plus methylation at diagnosis is not something most centers can order today. Still, this is the kind of biology that should eventualy decide who gets what up front. Great work by Magrangeas, Moreau, Touzeau, Avet-Loiseau, Minvielle, Letouzé and colleagues. #mmsm #Myeloma #MRD

Cassiopeia trial One of the first trials of Quad therapy and two randomization. Shows some interesting data points Evolving p value signifance from what we knew few yrs ago Certainly an older Imid ; but value in LMIC ? Can we just do quad and not have any Dara afterwords ? https://t.co/gWatWC3UVe

Impressive safety; tolerability while maintaining efficacy for BCMA directed bispecifics. Congratulations @PlasmaCellPete and the CERVINO team ! https://t.co/qKgIj04y92

Heading to #IMS26 ! Going through all the amazing abstracts, A few things on my radar this year so far: — CERVINO: first phase 3 readout for a BCMA bispecific vs standard-of-care in triple-class exposed RRMM — PERSEUS at 6+ years — does the PFS advantage for quad induction hold up long-term, and is there finally an OS signal? — Two separate first-in-human reports of in vivo CAR-T generation — no apheresis, no lymphodepletion. If this works, it changes how we think about access to cellular therapy entirely. — CARTITUDE-2 5-year data on cilta-cel in earlier-line RRMM — EXCALIBER-RRMM: iberdomide's first phase President of IMS - Prof Phillip Moreau and his executive team, @myelomaMD @mvmateos @NoopurRajeMD @NikhilMunshiMD have put together an amazing meeting with 669 abstracts and many amazing talks ! I will be tweeting important practice changing abstract through rest of week; excited for busy week :) #Myeloma #HemOnc #IMS2026 #glasgow

Heading to #IMS26 ! Going through all the amazing abstracts, A few things on my radar this year so far: — CERVINO: first phase 3 readout for a BCMA bispecific vs standard-of-care in triple-class exposed RRMM — PERSEUS at 6+ years — does the PFS advantage for quad induction hold up long-term, and is there finally an OS signal? — Two separate first-in-human reports of in vivo CAR-T generation — no apheresis, no lymphodepletion. If this works, it changes how we think about access to cellular therapy entirely. — CARTITUDE-2 5-year data on cilta-cel in earlier-line RRMM — EXCALIBER-RRMM: iberdomide's first phase President of IMS - Prof Phillip Moreau and his executive team, @myelomaMD @mvmateos @NoopurRajeMD @NikhilMunshiMD have put together an amazing meeting with 669 abstracts and many amazing talks ! I will be tweeting important practice changing abstract through rest of week; excited for busy week :) #Myeloma #HemOnc #IMS2026 #glasgow

The lowest dose won. Check out my article below👇👇👇👇 for a full breakdown FDA-approved iberdomide (first CELMoD) + subcutaneous dara + dex for myeloma after ≥1 prior line, on MRD-negative CR — 41% vs 21% with DVd, p&lt;0.0001. EXCALIBER-RRMM, n=939, phase 3: • Stage 1: 279 https://t.co/rq4WVA95YP https://t.co/fshIO7ZQB8