Today, I began at 4 a.m. PST for the privilege of being able to attend the International Myeloma Working Group (IMWG) meeting. The IMWG has more than 260 myeloma specialists who meet twice a year. Whenever you see a phrase such as “…responses per IMWG guidelines,” writing consensus guidelines (eg. defining “Very Good Partial Response”) is one of the IMWG tasks along with taking on research projects. IMF Chariman of the Board and Chief Scientific Officer Dr. Brian G.M. Durie started IMWG, which now has an esteemed board consisting of Chairman Durie along with multiple myeloma Drs. S. Vincent Rajkumar, Philippe Moreau, and Jesus San Miguel. Today’s agenda consists of previewing some ASH abstracts, embargoed until their ASH presentation, review of current projects and discussion of possible proposals…specifically producing future guidelines for myeloma treatment.
Then it was off to “virtually” attend a number of first day oral abstract presentations. The format of these fifteen-minute talks is for the primary investigator of the abstract to present their slides for 10 minutes and allow 5 minutes for questions. The hybrid nature of this year’s ASH where facilitators, presenters, and the audience is a blend of in-person and virtual makes a bit of a challenge. On the other hand, I’ll be watching both live talks as well as replays, so in fact, some of what gets presented today may not get reported by me until a later blog or saved for my ASH summary.
After the IMWG meeting, I attended an Education Program, this one providing talks on frail patients (it’s not just an age thing), high-risk (consider 1q gain (3 copies) and amp (4 copies) of 1q alone to both be HR), and Minimal Residual Disease testing. And, later in the day, I attended a second Education Program, “Immunotherapy in Multiple Myeloma,” which reviewed all the immunotherapy treatments for myeloma.
These are my highlights from today’s abstract presentations. I understand they’re fairly technical but that’s my style. You should consider checking out other patient blogs for more descriptive explanations.
Bispecific Antibodies
There continues to be bispecific updates and more will come on Sunday and Monday. The bispecifics often use 1-2 “step-up” doses (start with lower amounts) to mitigate potential Cytokine Release Syndrome (CRS). TECVAYLI™ (teclistamab-cqyv) was recently approved by the FDA, and talquetamab was just submitted to the FDA for approval. Typically, these bispecifics have high single-agent overall response rates (ORR), typically in the ranges of 60-80%. Yet, they also have common side effects, such as Cytokine Release Syndrome (CRS) and Infections.
Bispecific abstracts presentations consisted of:
1) Talquetamab-MonumenTAL-1 (GPRC5D x CD3) given subQ to N=105 patients across 3 cohorts…2 different dosages and a group of previous BCMA treatment recipients. Resulted in ORR 63-74% and importantly low infection rates (All:50-57%, G3/4:12-17%) compared with other bispecifics. [See ASH Abstract 157.]
2) Elranatamab-MagnetisMM-1 (BCMA x CD3) given every week or every other week subQ at dosages 215-1000mg/kg to N=55 patients heavily pre-treated (including prior BCMA) in the study. This resulted in ORR of 64% (ORR 54% for patients with prior BCMA therapy), mDoR of 17.1 months. When step-up dosing and pre-meds were implemented, CRS decreased from 87% to 67% with no G3/4, while G3/4 infections occurred in 21% and 5% respectively. [See ASH Abstract 158.]
3) Elranatamab-MagnetisMM-3 (BCMA x CD3) given weekly subQ 76mg with 2-step-up doses to N=123 patients. So far, the first week requires hospitalization like teclistamab-cqyv. After 2×28-day cycles, dosed every 2 weeks. ORR 61%, 9-mth DoR and 9-mth PFS were 84% and 63% respectively. All CRS (58%) were G1/2. Infections 67% (G3/4 35%). [See ASH Abstract 159.]
4) (Look familiar?) Elranatamab-MagnetisMM-5, Part 1 (BCMA x CD3). Elranatamab (44 or 76mg) + Dara (no dex!), both subQ, n=34. ORR 71%, All CRS (47%) G1/2. Part 2 will be Elra+Dara vs DaraPd for RRMM >= 1 LOT. [See ASH Poster 1921.]
5) Teclistamab Majestic-2 (one cohort) (BCMA x CD3): Tec+Dara+Rev (no dex!) for N=32 with 1-3 prior LOT. Tec dose was either .72 or 1.5 mg/kg, then 3mg/kg at cycle 3. ORR 94% (>= VGPR 90%). All CRS (81%) were G1/2. Infections 91% (G3/4 38%). Early data. Majestic-7 planned: TecDR vs DRd in NDMM. [See ASH Abstract 160.]
6) Forimtamig (RG6234) (GPRC5D x CD3): N=51 (IV) + 57 (subQ), 20% prior BCMA. ORR 67% (>=VGPR 56%). Treatment duration plan is 1 year. ORR for prior BCMA is 52%. mDoR 11 mos. (I’ve average IV and subQ results when small individual differences.) All CRS (80%) G1/2 (2 patients G3). Infections IV all 61%, (G3/4 22%); subQ all 46%, (G3/4 26%). [See ASH Abstract 161.]
7) Alnuctamab (BCMA x CD3). 2 years ago Celgene/BMS presented results for IV but CRS was high. Developed subQ to lower CRS. RRMM patients with >= 3 LOT. Dose expansion doses are 10 and 30mg. N=68. ORR 53% (>= VGPR 40%), although 30mg ORR 65%. All CRS (53%) were G1/2. Infections all 34%, (G3/4 9%). [See ASH Abstract 162.]
Other Abstracts
8) iStopMM (Iceland). [See www.myeloma.org for full explanation of iStopMM.] IgA MGUS behaves in contrast to other immunoglobulin subtypes with prevalence rising slowly with advancing age, if at all after age 70. [See ASH Abstract 103]
9) iStopMM (Iceland). After examining 1,814 MGUS mtg, there was no evidence of MGUS progression after Covid vaccination. [See ASH Abstract 105]
10) iStopMM (Iceland). They have developed a model to predict >= 10% Bone Marrow Plasma Cell (BMPC). Predictors are all accessed via blood (e.g. M-protein, IgG, IgA, IgM, FLC ratio). As such, many MGUS patients could defer Bone Marrow Sampling. [See ASH Abstract 107.]
11) From the Canadian Myeloma Group database, they examined 3821 myeloma patients who had an ASCT (8% had tandem) as frontline therapy during 2007-2021. Most induction was CyBorD (72%). mPFS about 36 mos (std-45; HR-28). 54% of patients received maintenance (mostly Rev). With Rev maintenance, mPFS=54 mos and mOS=159 mos (that’s 13+ yrs), which is a 4 yr OS improvement over no maintenance. HR maintenance had mOS 97 mos (64 mos with no maintenance). [See ASH Abstract 117.]
12) GEM-CESAR for HR SMM: N=90 patients did KRdx6-> SCT -> KRdx2 -> R up to 2 years. 23% of these patients were MRD- (NGF 10-5) 4 years after the SCT and 2 years after completing treatment. Could these patients be cured? [See ASH Abstract 118.]
13) KarMMa-2/Ide-cel/Abecma: CAR-T treatment for HRMM patients in cohort 2a (relapse within 18 mos after frontline SCT and maintenance). Treatment 150-450M (median dose 425M cells) Car-T cells. N=37 became 22 evaluable patients. ORR=84%, DoR 15.7mos (23,5 mos for CR patients). mPFS 11.4 mos, 2yr OS 85% was event-free. MRD- at 10-5 was 68% in all patients (85% in CR patients). All CRS (84%), only 1 pt grade 3/4. Infections 60% (G3/4 22%, 2 patients G5 who died). All in all, a favorable benefit-risk. [See ASH Abstract 361.]
14) BMS-986393 CAR-T that targets GPRC5D(!): RRMM patients, Ph1 first results, 5 dose levels 25M-450M, N=33 (>half prior BCMA, 39% previous BCMA CAR-T). ORR 90% but 100% at the higher doses. Prior BCMA ORR 80%. [See ASH Abstract 364]
15) GC012F is a BCMA/CD19 dual-targeting FasTCAR-T as first-line TE-eligible High Risk NDMM. N=16. ORR 100%, all >= VGPR (88% sCR). And 14 of 16 MRD- at 10-6 through month 12, long persistence. Only 25% CRS, all G1/2. Impressive data. [See ASH Abstract 366.]
That’s it for tonight. While my first meeting tomorrow isn’t till 7:30 a.m. PST, one benefit of a virtual ASH is that many sessions are recorded and available for replay.
Be your own best patient advocate.
— Jack Aiello, on Twitter @JackMAiello