2) This program, intended for #HCPs, is supported by an independent educational grant from Bristol Myers Squibb. Follow this 🧵for 🆓1.0h CE/#CME! Statement of accreditation & faculty disclosures at https://t.co/8oShcATovC. FOLLOW US for expert-led #MedEd in #hemeonc.
— @onc_ce (@onc_ce) June 1, 2026
3b) Survival with #MM has improved substantially in the era of triplets, quadruplets, cellular therapy, and T-cell engagers, but most patients ultimately develop treatment-refractory disease.
— @onc_ce (@onc_ce) June 1, 2026
5) That’s why next-gen therapies aim for deeper remissions, longer disease control, activity in refractory disease, ⬇️toxicity. New tx e.g. #CELMoD agents, bispecific antibodies, novel targeted degraders may extend survival while improving quality of life for patients with #MM.
— @onc_ce (@onc_ce) June 1, 2026
6b) . . . and redirecting the CRL4-CRBN ubiquitin ligase complex to degrade key transcription factors, especially #Ikaros (IKZF1) and #Aiolos (IKZF3).
— @onc_ce (@onc_ce) June 1, 2026
See 🔓https://t.co/MxK9rWYqLn 🔓https://t.co/R5yGfDGjk2 pic.twitter.com/0XApDTm2mL
7b) . . . enhanced T-cell and NK-cell activation, increased IL-2 production, and improved immune-mediated killing of #MM cells. See 🔓https://t.co/PfbSPyhoMM pic.twitter.com/BBLO27DoHy
— @onc_ce (@onc_ce) June 1, 2026
9) So what do you know already?#Iberdomide & #mezigdomide are best described as:
— @onc_ce (@onc_ce) June 1, 2026
A. BCMA #ADCs
B. Proteasome inhibitors
C. Oral #CELMoDs that enhance cereblon-mediated Ikaros/Aiolos degradation
D. Anti-CD38 mAbs
11) Which statement is accurate for #CELMoDs in heavily pretreated #RRMM?
— @onc_ce (@onc_ce) June 1, 2026
A. #Mezi-d showed #ORR ~41% in triple-class refractory pts
B. #Iber-d showed ORR ~80%
C. Both are approved frontline regimens
D. Neither is oral
13) But 1st we’ll focus on #mezigdomide (CC-92480), gen viewed as even more potent #CELMoD than #iberdomide, w/particularly deep IKZF1/3 degradation & activity in heavily pretreated #RRMM. Early & phase 3 studies ➡️meaningful efficacy even in highly refractory disease settings. pic.twitter.com/8gzzlv4Biu
— @onc_ce (@onc_ce) June 1, 2026
15) Compared with earlier #IMiDs, #mezigdomide was designed for potent and sustained Ikaros/Aiolos degradation, with pharmacodynamic data showing maximal #Aiolos degradation around 3 hours & suppression through 24 hours.
— @onc_ce (@onc_ce) June 1, 2026
17) Early clinical data with #mezigdomide+#dexamethasone in triple-class-refractory #RRMM showed an ORR of 40.6%, median PFS of 4.4 months, & median DOR of 7.6 months, with neutropenia & infection among the key toxicities.
— @onc_ce (@onc_ce) June 1, 2026
🔓 https://t.co/hiBAioMTr3 pic.twitter.com/TXFWSoAh1N
19) Your faithful correspondent and #MM expert faculty @SagarLonialMD was in the room at #ASCO26 on behalf of @onc_ce as Paul G. Richardson, MD (@DanaFarber) presented the Ph 3 #SUCCESSOR_2 primary analysis! pic.twitter.com/d1ZwyNWEd7
— @onc_ce (@onc_ce) June 1, 2026
21a) As shown, both drugs are being actively studied in #RRMM; #Iberdomide in combo with #daratumumab, a targeted monoclonal antibody #MAb used to treat #MM & #AL_amyloidosis.#Mezigdomide is primarily used in combo with dexamethasone & a proteasome inhibitor …
— @onc_ce (@onc_ce) June 1, 2026
22) Why does this trial matter? More #MM pts arrive at relapse already exposed to anti-CD38 mAbs AND lenalidomide. That dual exposure carries a median PFS of just 6.3 mo, so highly effective, convenient options for these pts are urgently needed. #ASCO2026 #SUCCESSOR2 pic.twitter.com/peQorfA8y5
— @onc_ce (@onc_ce) June 1, 2026
24a) #SUCCESSOR2 design: a 2-stage phase 3 trial. Stage 1 optimized the #Mezi dose; Stage 2 randomized 479 pts 3:2 to #MeziKd (1.0 mg Mezi PO daily D1–21 + weekly IV #carfilzomib) vs #Kd.
— @onc_ce (@onc_ce) June 1, 2026
Primary endpoint: #PFS per #IRC.
Key secondary: #OS. #ASCO2026 #RRMM pic.twitter.com/gn41Lb1Ep8
24b) Note: More patients were randomized to #mezigdomide. There were 2 additional key eligibility criteria:
— @onc_ce (@onc_ce) June 1, 2026
👉Minimal response or better to ≥1 prior therapy
👉K- and Mezi-naïve
26) Treatment exposure was encouraging. At median follow-up of 10.6 months, 52% of #MeziKd pts remained on therapy vs 31% on #Kd. Mezi relative dose intensity held at 83%, with discontinuations due to AEs infrequent at 9.7%. #ASCO2026 #SUCCESSOR2 #RRMM pic.twitter.com/cii1kAIMEi
— @onc_ce (@onc_ce) June 1, 2026
28) The #PFS benefit was consistent across ALL prespecified subgroups, regardless of age, #ISS stage, #cytogenetic risk, refractory status (anti-CD38, #LEN, or both), number of prior LOTs, or presence of extramedullary disease. No subgroup favored Kd. #ASCO2026 #SUCCESSOR2 pic.twitter.com/3qaNXPsKSs
— @onc_ce (@onc_ce) June 1, 2026
30) Beyond 1st progression: #MeziKd also showed superior #PFS2 (23.6 vs 13.0 mo; HR 0.53), w/only 24% of MeziKd pts requiring subsequent therapy vs 50% on #Kd. #OS data remain immature (HR 0.79), with no crossing of curves at this early futility analysis. #ASCO2026 #SUCCESSOR2 pic.twitter.com/0H3qm9jeiV
— @onc_ce (@onc_ce) June 1, 2026
32) Bottom line from Richardson et al #ASCO2026: #MeziKd significantly improves #PFS with a manageable safety profile in anti-CD38 mAb– and LEN-exposed #RRMM. Oral #mezigdomide + weekly IV carfilzomib represents a potential new standard of care, including in community practice. pic.twitter.com/yBUPGZIFT4
— @onc_ce (@onc_ce) June 1, 2026
34) From a pt safety aspect, awareness for #neutropenia (not new or unexpected) is 🔑, but the use of #G_CSF early on can mitigate this side effect & does not interfere with treatment or efficacy. There is no concern for giving #Mezi and G-CSF at the same time.
— @onc_ce (@onc_ce) June 1, 2026
36) But wait, there's more! As teased before, there has been new data presented on #iberdomide in #MM at #ASCO26 as well! pic.twitter.com/sYd2OALCOK
— @onc_ce (@onc_ce) June 1, 2026
38) Why swap #lenalidomide for #iber in #NDMM? Iber has been shown to have superior synergy with #daratumumab compared to #LEN. Current #DVRd is given continuously; can a CELMoD change that? #ASCO2026 #IDEAL pic.twitter.com/Qm7i843gQG
— @onc_ce (@onc_ce) June 1, 2026
39b) Ph 1 identified the #RP2D; Ph 2 tested 12 cycles of #Iber_DVd induction → fixed-duration #iber maintenance (C13–36). Primary Ph 2 endpoint: #CR rate by mass spectrometry. #ASCO2026 #IDEAL pic.twitter.com/kyKLly44S9
— @onc_ce (@onc_ce) June 1, 2026
41a) Responses were deep & kept deepening. #ORR 100%. At end of induction: #CR 43%, #MRD-neg (10⁻⁵) 34%. At deepest assessment: CR 57%, MRD-negative 52%.
— @onc_ce (@onc_ce) June 1, 2026
42) Survival data at 22.8 months median follow-up are striking. Median #PFS not reached; 18-month PFS 88.9%. Median #OS also not reached; 18-month OS 94.5%. These are the FIRST survival data reported for a #CELMoD-based quadruplet in #NDMM.#ASCO2026 #IDEAL #multiplemyeloma pic.twitter.com/Xnev31PAnw
— @onc_ce (@onc_ce) June 1, 2026
44a) Bottom line from @MyelomaDrKapoor et al at #ASCO2026: Fixed-duration #Iber_DVd → #iber maintenance is effective in TD & TIE #NDMM.#RP2D: 0.75 mg/day.
— @onc_ce (@onc_ce) June 1, 2026
45) Here’s the #IDEAL perspective of @SagarLonialMD:
— @onc_ce (@onc_ce) June 1, 2026
Very important evidence that you can move #iber to front line therapy as part of a quad and demonstrate ⬆️efficacy & tolerability compared w/the same quad using #lenalidomide.
47) Also, Tanya Wildes MD from @unmc presented "Iberdomide Maintenance Following Upfront #ASCT in MM" on June 1. pic.twitter.com/mSoIjp36n7
— @onc_ce (@onc_ce) June 1, 2026
49) 38 pts with #MM, ≥PR at day 80–110 post-#ASCT, received #iber 1.0 mg PO D1–21 of 28-day cycles until PD or toxicity. In this group, 97% had rec'd LEN and 84% DARA during induction. At enrollment, 87% were already MRD-negative. A high bar to clear . . . but . . .
— @onc_ce (@onc_ce) June 1, 2026
51) Primary tolerability challenge: #neutropenia. Most common gr 3/4 #TEAE (gr 3 n=19, gr 4 n=5; 🚫G-CSF per protocol). Within yr 1, 29% d/c'd, for neutropenia (n=5) PD (n=3) & rash (n=1). Authors note lower starting dose, G-CSF use, & flex neutropenia mgmt could ⬆️retention. pic.twitter.com/bKrFt4Jw8f
— @onc_ce (@onc_ce) June 1, 2026
53a) Comments from @SagarLonialMD:
— @onc_ce (@onc_ce) June 1, 2026
This is really important & adds to the evidence from the #EMN26 study (see 🔓https://t.co/ov9lqJ2Sih) that #iber maintenance can enhance depth of response & is a good option, also w/⬆️ safety profile & tolerance when compared with #len.
54) Let's start to wrap up with a practical comparison of these (still investigational CELMoD) agents:
— @onc_ce (@onc_ce) June 1, 2026
👉#Iberdomide → broader clinical development footprint, earlier-line combinations, strong immune stimulation profile
56) At #ASCO26 @SagarLonialMD says we gained imp't new insights into their potential best use in #MM: After yrs of early trials showing ⬆️efficacy, ⬆️immune stimulating effects, & a better safety profile for #CELMoDs vs #IMIDs, we see the approval lights at the end of the road.
— @onc_ce (@onc_ce) June 1, 2026
58a) In this era of immune treatments, having agents that not only directly target #MM through a different mechanism, but also enhance #immunity (making other immune targeted treatments more effective) . . .
— @onc_ce (@onc_ce) June 1, 2026
59) And . . . congratulations! You are not only up to date from #ASCO26 on #CELMoD therapy for #MM, you also just earned 1 hour of 🆓CE/#CME credit! Claim your certificate now at https://t.co/3p9nd2Sa9I.
— @onc_ce (@onc_ce) June 1, 2026
Many thanks to our 🏆expert faculty @SagarLonialMD @EmoryMedicine!