Tuesday was the final day of ASH with a Late-Breaking Abstract, and Monday had many myeloma talks presented simultaneously. As such, the rest of Tuesday I spent watching replays of many Monday talks. Now it’s Wed-Thu and, to be honest, I’m a bit brain-fried. There were Education Programs, so many abstracts, and even a live Facebook ASH update forum presented by IMF Chief Medical Officer Dr. Joseph Mikhael.

Now to some of those most impactful abstracts. [Dr, Abstract#]:

1. I’m starting with the Late-Breaking Abstract because it was deemed quite important. This was a phase III study or Darzalex (daratumumab), plus Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone, or Dara+RVd vs RVd followed by stem cell transplant (SCT), consolidation, and maintenance (DR or R, and minimal residual disease negativity, or MRD-, after 12 months, Dara was deleted. This was put on by the European Myeloma Network (EMN) made up of 130 institutions, and 11 countries (including Australia). For N=709, the Dara arm exceeded the non-Dara arm in every measure: 4 yr median progression-free survival (mPFS): 84% v 68%; CR 88% v 70%; MRD- (10-6 ) 65% v 32%. And 64% of the Dara maintenance arm was able to stop the Dara, although I don’t know the relapse rate. (It’s pretty clear that between this and the Plenary talk, the 4-drug regimen is here to stay for Transplant-eligible patients…that is until CAR-T’s take over.) [Sonneveld, LBA-1]
2. In an Education Program, Dr. Surbhi Sidana (Stanford University — Stanford, CA) reviews toxicities associated with Bispecifics (BsAbs). If Cytokine Release Syndrome (CRS) is experienced, she encouraged the use of Tocilizomab, which itself does not add to other side effects. If ICANS (neurotoxicity) is experienced (20% CAR-T, 5-10% BsAbs) both steroids and Anikinra are effective. About 3-4 weeks out, about 6% of Abecma patients experience Parkinsonism (don’t really know how to treat…maybe steroids, cytoxin?); and 6% of Carvykti patients experience Bells Palsy (facial droop), which tends to resolve itself. Finally, both CAR-T and BsAb’s cause high rates of cytopenias (blood count reductions) and Infections, except lower rates in GPRC5D cell therapy. Expect to take prophylactics for infection and IVIG. GPRC5D also causes side effects to skin (both rash, non-rash), nails, and dysgeusia (loss of or altered taste).
3. Eque-cel, another BCMA CAR-T from China, showed good results in a phase II trial (FUNMANBA-1) for N=88 pts, with 3 or more prior LOTs. The focus of this study was on outcomes and characteristics of patients who achieved sustained MRD- (10-5). Overall 94% achieved MRD- and 81% had sustained MRD- for >= 12 months. Factors that impacted sustained MRD were High Risk, BCMA expression, and bridging therapy. There was only a weak correlation between persistence and MRD- duration. [Li, 761]
4. We saw earlier studies called DETERMINATION and IFM2009 that delayed SCT to first relapse resulted in similar efficacy to up-front SCT. The GMMG Relapse trial is randomized to compare Salvage SCT to continuous Rd. However, after an 8-yr follow-up, there was no significant progression-free survival (PFS) or overall survival (OS) difference. [Baertsch, 782]
5. This study examined low-risk smoldering multiple myeloma (SMM) (M-protein <2g/dL and Free Light Ratio <20). Their results showed that patients with an evolving MP (>=0.4g/dL) and eFLR (>= 40 increase) was associated with a median time to progression of 25 months, the same as high-risk patients at baseline. [Akhlaghi, 877]
6. A study of focal lesions at diagnoses for N=194 pts showed no Free Lights (FLs) 20%, FLs by DW-MRI 12%, and FLs by MRI & PET 69%. Post-SCT results show 69%, 25%, and 6% respectively. FLs after SCT are prognostic for poorer outcomes, and treatment should be more than standard maintenance even if the response is excellent. [Schinke, 882]
7. I mention this study because it’s the first trial result to come out of the Asian Myeloma Network (AMN) established in 2011 by the IMF. Today it consists of 10 countries and 160 members. They compared Pomalyst (pomalidomide), Cytoxan (cyclophosphamide) and dexamethasone (PCd) vs Pd for N=122 relapsed/refractory multiple myeloma (RRMM) patients with a median of three lines of treatment (LOT). The results were that PCd improved mPFS (11 v 6mos), overall response rate or ORR (61 v 38%), and Duration of Response. [Chng, 1009]
8. Dr. Ajai Chari (University of California — San Francisco) presented efficacy and safety results of lower Talvey (talquetamab) dosing. Today, the approved recommended dose is 0.4 weekly or 0.8 every other week. Side effects from this MonumenTAL-1 study included dysgeusia=77%, skin (such as peeling)=73%, nail=63%, and skin (rash)=40%. Interestingly, these side effects were not seen when talquetamab was being tested at lower doses. N=25 dose-reduced to 0.4 every 2 weeks or N=10 dose-reduced to 0.8 every 4 weeks. Responses compared favorably versus original dosing: ORR (79 v 72%); 12mos PFS (50 v 54%). And side effects decreased across the board, and no new side effects. [Chari, 1010]
9. Sonrotoclax is a next-generation Venetoclax inhibiting BCL2 with a potency >10x. Sonrotoclax 640mg plus dex was given to N=10 R/RMM pts harboring t(11;14). ORR was 70% (7 of 10) for this small group of patients.[lQuach, 1011]
10. HPN217 is a tri-specific, targeting CD3 on the T-cell and both BCMA and albumin on the multiple myeloma cell, the latter for increased half-life extension (longer persistence). In this phase 1 trial for N=97 R/RMM pts, 12 mg dose resulted in ORR=63% so will be the recommended phase II dose. [Madan, 1012]
11. Mezigdomide (a CELMoD, known as Mezi) plus dex plus either Darazalex (daratumumab) or Emplicit (elotuzumab) were compared. For RRMM patients with 2-4 prior lines of treatment. For N=79 on varying dosages of Mezi, the MeziRd and MeziEd ORR’s were 75% (although one of the doses was 89%) and 45% respectively. However grade 3/4 AE’s MeziRd and MeziEd were 77% and 95% respectively, with neutropenia and infection having the highest impact. [Richardson, 1013]
12. First results of the phase Ib MonumenTAL-2 study were shown. Talquetamab and pomalidomide were given to N=35 RRMM patients. As was shown earlier, talquetamab is either given weekly (QW) or every other week (Q2W). ORR was 94% and 84%, >=CR was 63% and 37%, and >=VGPR was 88% and 69% respectively. There was 23% grade 3/4 infections. [Matous, 1014]
13. We now have longer study results for CARTITUDE-2 CAR-T trial with a follow-up of 29 months, Cohort A N=20 Rev-refractory 1-3 LOTs and Cohort B N=19 1 prior LOT. Originally reporting 95% and 100% ORR for the 2 groups, MRD- at 10-5 shows 100% and 93% respectively. And sustained MRD >12 mos was 52% and 62% respectively. Finally, 2 yr PFS was 75% and 73% while 2 yr OS was 75% and 84%. Neutropenia Grade 3/4 was about 95% and 90%. [Hillengass, 1021]
14. Updated results were also provided for GC012F FasTCAR-T (24-hour production) targeting BCMA and CD-19 for N-22 first-line newly diagnosed multiple myeloma (NDMM) patients. They achieved 100% ORR and complete response (CR) as well as 100% MRD- at 10^-6. No grade 3/4 CRS or ICANS. [Lu, 1022].
15. Another new CAR-T study presented CART-Ddbcma for N=38 for RRMM with >=3 LOTs. The “Dd” apparently stands for “domain” reflecting a more stable binding. With 1 yr of follow-up, ORR=100% (>=VGPR 92%), and 2yr PFS of 56%. MRD at 10-5 was 89%. Importantly, the efficacy rates were similar for high-risk patients. As a phase II trial, this will come from Kite Pharma and be called iMMagine-1, now enrolling. [Frigault, 1023]
16. And, we have yet another new BCMA CAR-T ARI0002h that included a booster dose at day 100 for N=60, >=2 LOTs but no prior BCMA. ORR was 95% within first 3 months and MRD at 10^-6 on days 28, and 100 were 98% and 96% respectively. The estimated mPFS was 16 months, which was also the case for HRMM. [Oliver-Caldes, 1026]
17. Dr. Sidana (Stanford University — Stanford, CA) showed real-world results for Ide-cel using the CIBMTR database with 821 RRMM patients, three-fourths of whom would have been ineligible for the ide-cel trial. Overall, both efficacy and ASE results were very similar to the KarMMa trial. ORR was 78%, mPFS was 9 mos and 1yr OS est=67%. It should be noted that prior use of BCMA (ADC or BsAb) resulted in lower PFS and OS by a few months. [Sidana, 1027]
18. Here’s a very interesting study that examine dex dose reduction in the large SWOG trials S0777 and S1211 which both had pts using dex at the 40mg dosage. However, more than half the patients dose-reduced without changing their PFS and OS outcomes. Perhaps 40mg of dex is not needed for the entire length of induction. [Banerjee, 1066]
19. We know that infection rates are high with immunotherapy treatments. This study looked at RRMM patients treated with either anti-BCMA (N=200) or anti-GPRC5D (N=29) bispecifics. Overall infection types are bacterial (56%), viral (38%), fungal (5%) and parasitic (1%). BCMA v GPRC5D infection rates were 73 v 53%. To reduce infection rates, minimize steroid use and space out injections. [Cellerin, 1005]
20. This CAR-T study focuses on patients with extramedullary (tumors separated from the bone) and paramedullary (tumors attached to the bone) disease. It compared N=134 pts, 75 with neither, 34 with EMD, and 25 with PMD. It runs out that the presence of extramedullary, but not paramedullary, was associated with significantly worse PFS and OS. For example, mPFS was 24mos, 12 mos, and 26 mos respectively. And the OS risk was 4 times as great. [Pan, 1006]

Well, that’s it for 2023 ASH, although I feel there are topics that need to be more completely shared such as genomics, diversity, nutrition, frailty, and more. Still, the amount of coverage on CAR-T, bispecifics, real-world comparison, and transplants dominated the coverage for me. Fortunately, I know there will be webinars offered by the wonderful myeloma advocacy organizations that help us stay informed about myeloma. This “virtual” hybrid platform worked for the most part, though I do miss connecting face-to-face with others. I hope this will happen at the 2024 ASH conference, also in San Diego. I’m sincerely grateful to our pharma partners BMS, Janssen, Karyopharm, Regeneron, and Takeda for sponsoring the IMF and enabling me to attend!

At the public Facebook event at the end of ASH, I asked Dr. Joe Mikhael “When will we have personalized medicine for multiple myeloma patients?” His answer expressed that we’re already there in this respect. When he sees a patient, he studies the patient’s myeloma, past treatments, treatment responses, comorbidities, and goals/desires. Only after that is it appropriate to discuss and consider a treatment option. And with 19 FDA-approved multiple myeloma treatments in the last 20 years, and many more combination therapies as well as so many trials, we have a better chance than ever before of providing the patient with an excellent treatment.

Be your own best patient advocate.

— Jack Aiello, on Twitter @JackMAiello