2/Multiple Myeloma trials: Industrial trials constitute the largest proportion of MM trials (40%), followed closely by AS trials (37%).
Phase 2 trials are also the most common (61%), with AS leading in this phase (44%). However, industry significantly dominates both Phase 1 (54%) and Phase 3 (62%) MM trials. This suggests a greater industry focus on early-stage exploration and late-stage validation.
3/A much larger number of patients (112,419) enrolled in MM trials. IS trials accounted for the overwhelming majority of patient enrollment (65%), demonstrating a substantial dominance in this area. AS, NIHS, NS, and MS trials enrolled significantly fewer patients. Enrollment in IS trials has consistently led since 2001.
🧵Intrathecal chemotherapy for ciltacabtagene autoleucel-associated movement and
neurocognitive toxicity
1/ Cilta-cel-associated parkinsonism is a rare but serious delayed toxicity
*🚨Incidence reported in this study was 8% (5 cases out of the first 60 consecutive patients).
♾️ Previous studies cited show varying incidence rates: 6% in CARTITUDE-1, 1% in CARTITUDE-4, and 2% in commercial cilta-cel treatment.
#mmsm #myeloma #MedEd #medtwitter #USMIRC @USMIRCNEWS @OncoAlert #المايلوما #سرطان_الدم
2/🌡️ Characteristics of Cilta-cel-associated Parkinsonism: The onset is typically subacute, emerging approximately 1-2 months after CAR T-cell infusion.
**The median time to onset in this study was 26 days (range 9-36).
⚛️ Common symptoms observed in all 5 pts included personality changes (flat affect, anhedonia, avolition), difficulty with word finding, masked facies, anosmia, resting tremor, rigidity, impaired swallowing, micrographia, bradykinesia, & shuffling gait.
3/🧪 The study highlights the presence of CSF lymphocytosis, primarily comprised of T-cells, in patients experiencing MNTs.
- The median CSF WBC count was 42/μL (range 2-140), with 80% of patients showing CSF pleocytosis (>5 WBC/μL).
- The median CSF lymphocyte percentage was 90% (range 89-95%), with FC confirming these were almost exclusively T-cells.
- 🚦 This finding is significant as it suggests CAR T-cells are trafficking into the CSF.
🚨🚨Very important Concept: ISB 2001, a novel BCMAxCD38xCD3 trispecific antibody from the first-in-human phase 1 study in RRMM:
1/ ISB 2001 is a novel trispecific TCE Ab designed to target three key antigens: BCMA & CD38 (on myeloma cells), & CD3 ( T-cell receptor complex)
#mmsm #myeloma #MedEd #MedTwitter #USMIRC @USMIRCNEWS @OncoAlert #سرطان_الدم #المايلوما
2/ ⚜️Study Design: ISB 2001 is administered weekly SC with a step-up dosing strategy (D1 & D4) followed by the full target dose (D8 onwards).
- Patient Population and Doses: 21 pts have been treated across 7 dose levels (5-1200 µg/kg).
- Across the effective dose levels (50-1200 µg/kg), the ORR was remarkably high at 89.5% (n=19).
ORR in patients previously treated w T-cell-directed therapy was 78% (n=9), suggesting efficacy even in this difficult-to-treat subgroup
3/⚛️ PK data up to 1200 µg/kg showed a dose proportional increase in serum exposures. A tentative half-life of > 10 days was observed, which "supporting the potential for less-frequent dosing
- Pharmacodynamics & Biomarkers:Rapid Reduction in Serum sBCMA levels & circulating B-cell counts were reduced rapidly within the first 2 treatment cycles
🧵Anti-GPRC5D CAR T-cell therapy as a salvage treatment in patients with progressive multiple myeloma after
anti-BCMA CAR T-cell therapy: a single-centre, single-arm, phase 2 trial
1/🚨Study Design: Single-centre, single-arm, phase 2 trial
• 37 patients with RRMM who had progressed after previous anti-BCMA CAR T-cell therapy, aged 18–70 years, with a Karnofsky Performance score ≥ 50.
*Patients were heavily pre-treated, with a median of 6 previous LOT. 59% had triple-class refractory disease!! (Not totally heavily treated IMO) ⚛️
2/Treatment: Single IV dose of anti-GPRC5D CAR T cells at 2 × 10⁶ cells per kg.
•Primary Endpoint: ORR based on IMWG.
•♦️Key Efficacy Finding: ORR was 84% (95% CI 68–94, 31 of 37 patients).
13 (35%) CR (8 sCR, 5 CR).
^^Response in Biochemical Progression: Responses were observed in 91% (10 of 11) of pts with only biochemical progression after anti-BCMA CAR T-cell therapy, including 64% (7 of 11) w CR
3/🧭 Comparison to Previous Salvage Therapies: In a post-hoc analysis of 14 patients who received subsequent antimyeloma therapies (CD38 antibody-based, carfilzomib-based, or selinexor-based) after anti-BCMA CAR T-cell progression, the ORR was 21% (3 of 14) 👎. The ORR of anti-GPRC5D CAR T-cell therapy in these same 14 pts was 71% (10 of 14), which was significantly higher (p=0·039). 👍🏻
- 20 (54%) of 37 patients achieved MRD-negativity.
- 🍋 mPFS in the entire cohort was 4·5 months (95% CI 2·9–6·2). PFS was not reached in pts with CR
#mmsm #myeloma #MedEd #MedTwitter #USMIRC @USMIRCNEWS @OncoAlert #سرطان_الدم #المايلوما
🧵A German multicenter real‐world analysis of talquetamab in 138 patients with relapsed/refractory multiple myeloma
1/Real-World Effectiveness of Talquetamab:
- In 123 evaluable patients, the overall response rate was 65%, with 26% achieving a nCR or better.
- PFS was 6.4 months
- Median DOR was 12.7 months (95% CI 9.5–NE).
- Median OS was not reached at the time of data cutoff.
#mmsm #myeloma #USMIRC @USMIRCNEWS @OncoAlert #MedTwitter #MedEd #سرطان_الدم #المايلوما
2/High-Risk Patient Population:♣️
•43% had ISS stage III disease.
•37% had extraosseous disease.
•48% had high-risk cytogenetics.
•The median number of prior therapy lines was 6.
•58% of patients would not have been eligible for the MonumenTAL-1 trial based on its inclusion and exclusion criteria, primarily due to cytopenias, renal dysfunction, and recent anti-tumor therapies.
•86% were triple-class refractory, & 47% were penta-drug refractory.
•48% had prior exposure to T-cell redirecting immunotherapy, with 20% having received a prior BTCE (mostly teclistamab) and 34% prior CAR T-cell therapy.
3/♻️Safety Profile in Real-World Practice:
•CRS occurred in 70% of patients, with 5.1% experiencing grade ≥ 3 events.
•ICANS occurred in 9% of patients, with 1.5% experiencing grade ≥ 3 events.
•The rates of severe CRS & ICANS were numerically higher compared to the MonumenTAL-1 trial.
Compared to the trial cohort, lower rate of tocilizumab administrations (35% vs. 55%; p = 0.03) & an increased use of steroids (20% vs. 7%; p = 0.06).
💰💲Economic Impact of Elranatamab for Treatment of Patients with Relapsed or Refractory Multiple Myeloma
💲Erlantamab cost over $19k/month!
1/ The estimated eligible population for elranatamab treatment within a one-million-member health plan is small: 14 patients per year for commercial plans and 60 patients per year for Medicare.
#mmsm #MedTwitter #MedEd #USMIRC @USMIRCNEWS @OncoAlert #سرطان_الدم #المايلوما
2/ The introduction of elranatamab is projected to increase total costs by $553,607 over three years, resulting in a per member per month (PMPM) increase of $0.05.
The total budget impact is estimated at $2,351,515 over three years, with a PMPM increase of $0.20
The primary driver of increased costs is the acquisition and administration of elranatamab, which replaces lower-cost regimens in the PCT basket.