Today began at 6:30 a.m. PST for the privilege of being able to attend the International Myeloma Working Group (IMWG) meeting. The IMWG has about 300 myeloma specialists who meet twice a year. Whenever you see a phrase such as “…responses per IMWG guidelines,” writing consensus guidelines (e.g. defining “Very Good Partial Response”) is one of the IMWG tasks along with taking on research projects. Dr. Brian G.M. Durie of the IMF started IMWG which now has an esteemed board consisting of Chairman Durie along with MM doctors S. Vincent Rajkumar, Philippe Moreau, and Jesus San Miguel. Today’s agenda consists of previewing some ASH abstracts, embargoed until their ASH presentation, reviewing current projects, and discussing 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 15-minute talks is for the primary investigator of the abstract to present their slides for 10 minutes and allow 5 minutes for questions. Given the hybrid nature of ASH, 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 talks categorized:

• Redirecting Therapy Outcomes and Associated Complications
• Prospective Trials: Smoldering and Newly Diagnosed Myeloma
• MRD and Alternative Non-invasive Bio Marker Evaluations
• A few key posters

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. [Dr, Abstract#]

Redirecting Therapy Outcomes and Associated Complications

1. This abstract examined “real-world” safety and efficacy of Teclistamab. You’ll see the term “real-world” used to mean patient results after FDA approval who are taking the treatment commercially approved. In fact, many of these patients (83% in this case) would have not qualified to be in the registration trial (MajesTEC-1) that resulted in Teclistamab’s approval. For N=106 pts, overall response rate (ORR) was 66% (ORR for MajesTEC-1 was 63%]. Further ORR’s for prior BCMA usage were 50%, 57%, 80%, and 33% for patients who had an antibody drug conjugate (ADC), CAR-T, ADC + CAR-T, or ADC+other respectively. [Dima, 91]
2. Health-Related Quality of Life (HRQoL) analysis of the large KarMa 3 study which randomizes patients into Abecma arm (N=254) or Standard of Care arm (N=132). Using several Patient Reported Outcomes (PROs) studies, fatigue, pain, and physical and cognitive functioning were all better in the CAR-T arm. [Delforge, 96]

Trials for Smoldering and Newly Diagnosed Myeloma

Immuno-PRISM: A small study (N=19, 12 evaluable) where Teclistamab is given the high-risk smoldering multiple myeloma (HR-SMM) (2-3 factors using 20-2-20) patients. Complete response (CR) for 10 of 12, very good partial response (VGPR) for other 2. 100% MRD- at 10-6. Longer-term results will be interesting. [Nadeem, 206]

This study looked a newly diagnosed HR MM pts (N=50) who received Darzalex (daratumumab), Kyprolis (carfilzomib) Revlimid (lenalidomide), and dexamethasone (DKRd) induction followed by a tandem stem cell transplant (SCT) plus consolidation (on between transplants as well as after the 2nd one) followed by 2 yrs Dara-Rev maintenance. This is an aggressive treatment for patients and resulted in 42% discontinuation. Efficacy results showed 94% MRD- (10-6), 30mo PFS = 80% and 30mo OS=91%. [Touzeau, 207]

For N=120 (40 per dosage cohort), Iberdomide (an oral Celmod) may well be an effective maintenance treatment following an SCT. During the first 6 cycles of maintenance, at the 1.3mg dose, CR improved from 28% to 53%. At the 1.0mg dose, CR increased from 25 to 40%. [van de Donk, 208]

Multiple Myeloma: Minimal Residual Disease (MRD) and Alternative Non-invasive Biomarker Evaluations

1. For N=54 HR SMM pts, this effective treatment of KRd (8 cycles) followed by Rev maintenance (2 years) showed sustained MRD negativity. With a median follow-up of 5 years, 93% of patients show no progression and 40% are MRD- (10-5) for at least 2 years. [Hill, 337]
2. Venetoclax (Ven), not yet approved for Myeloma but available off-label, continued to show good results for t(11;14) RRMM pts. For N=55 pts in the Ven-Dara-dex (VenDd) arm vs N-26 in the Dara-Vel-dex (DVd), VenDd showed superior ORR (96% v 65%) and mPFS (46 v 15 months). MRD negativity at 10-5 and 10-6 respectively were 40 v 24% and 24 v 6%. [Bahlis, 338]
3. This study focused on 3 different serum studies that could possibly replace MRD measured via bone marrow aspirates. BloodFlow, CloneSight, and QIP-MS (Mass Spec) can detect MRD with sensitivity to PB (Peripheral blood), cfDNA (circulating-free DNA), and serum respectively. There’s a 79% concordance between BloodFlow and Bone Marrow. Can’t wait till a blood draw becomes a standard way to measure MRD. [Gonzalez, 339]

Other Orals

1. BMS-986393 is a GPRC5D CAR-T about to enter ph 2 with a dosage of 150M reengineered t-cells. Overall results from ph 1 with varying dosages for N=84 pts (including 41% High Risk, 46% prior BCMA) 88% ORR as well as 83% ORR for HR pts. At the RP2D with N=26, ORR was 91% (CR 48%) and infections were relatively low at 35% and 12% for grades 3/4. [Bal, 219]
2. This presentation actually discussed the development of a CAR-T to increase persistence and long-term efficacy. Out of this came 2 CAR-T’s: a) BCMA D8 Fab CAR and 2) a dual targeting B cell maturation antigen (BCMA) and CD19 AUTO8 CAR. They are tested against each other in the MCARTY study, which is still recruiting for phase I (11 patients have in induced so far). At a median follow-up of 6 months, there were no reported cases of ICAN, no grade 3/4 cytokine release syndrome (CRS), 100% ORR with 2 cases of ongoing stringent Complete response, or sCR>12 months. Something to watch. [Lee, 350]

Posters

1. This poster updates Phase 1 results for Alnuctamab, a BCMAxCD3 bispecific from BMS. For N=73 (44 pts at 30mg or >30mg) subcutaneous (subQ) ALNUC appears safe with a low rate of severe infections at 62%/16% of patients. Across doses, responses were durable and deepened over time, with 100% of CR responders achieving MRD negativity (10−5 ). High antitumor activity was observed at target doses ≥ 30 mg (ORR 63%) and specifically at the 30-mg target dose (ORR 69%). [Bar, 2011]
2. Blenrep + Kd was given in a Ph I/II N=65 relapsed/refractory multiple myeloma (RRMM) patients. Blenrep was only given once every 2 mos. Treatment-related adverse events (AEs) were reported in 93% of pts (Gr3 60%, Gr4 13%), including blurred vision (40%, 7.3%, 0%). Ocular AEs occurred in 42 (79.2%) out of 53 evaluable pts including a decline in best corrected visual acuity (BCVA) (total 77.2%, Gr1 9.4%, Gr2 33.9%, Gr3 33.9%) and keratopathy (K) (total 75.4%, Gr1 5.6%, Gr2 22.6%, Gr3 47.2%). The preliminary efficacy data is encouraging with deep responses observed after only 2 cycles of therapy. ORR and ≥ VGPR by the end of cycle 2 were 80% and 40% respectively. [Lasica, 2012]

That’s it for tonight, and my first meeting tomorrow isn’t till 7:30 a.m. PST, so I get to sleep in a bit.

Be your own best patient advocate.

— Jack Aiello, on Twitter @JackMAiello