🧵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.

#mmsm #myeloma #MedEd #medtwitter #USMIRC @USMIRCNEWS @OncoAlert #المايلوما #سرطان_الدم

🚨🚨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

#mmsm #myeloma #MedEd #MedTwitter #USMIRC @USMIRCNEWS @OncoAlert #سرطان_الدم #المايلوما

🧵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) ⚛️

#mmsm #myeloma #MedEd #MedTwitter #USMIRC @USMIRCNEWS @OncoAlert #سرطان_الدم #المايلوما 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

#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.

#mmsm #myeloma #USMIRC @USMIRCNEWS @OncoAlert #MedTwitter #MedEd #سرطان_الدم #المايلوما

💰💲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.

#mmsm #MedTwitter #MedEd #USMIRC @USMIRCNEWS @OncoAlert #سرطان_الدم #المايلوما

🧵Primary Cell Leukemia ⏳Outcomes of hematopoietic stem cell transplantation in primary plasma cell leukemia: A systematic review and meta-analysis

1/ The study, which analyzed data from 12 original articles encompassing 1757 pPCL patients, highlights that while HCT remains a crucial treatment modality for this rare & aggressive hematologic malignancy, significant challenges persist
#mmsm #myeloma #MedEd #MedTwitter @OncoAlert #USMIRC @USMIRCNEWS @US_HMC 2/Auto-HCT demonstrates improved overall survival compared to historical outcomes, but is limited by high relapse rates. GO TO POST 4 ♦️
Allo-HCT carries a higher risk of treatment-related mortality and GVHD GO TO POST 5 ♣️

#mmsm #myeloma #MedEd #MedTwitter @OncoAlert #USMIRC @USMIRCNEWS @US_HMC

🚨Efficacy and safety of daratumumab in intermediate/ high-risk smoldering multiple myeloma: final analysis
of CENTAURUS 🧵

Find the Card ♠️ That indicates most important post in this thread!

1/ 👑The CENTAURUS study was a randomized, open-label, multicenter phase 2 trial designed to evaluate
if daratumumab monotherapy could delay the progression from intermediate- or high-risk SMM to symptomatic MM & to inform the optimal dosing schedule for the phase 3 AQUILA study

#USMIRC #MedEd #MedTwitter @OncoAlert @USMIRCNEWS #mmsm #myeloma #سرطان_الدم #المايلوما 2/⏳123 eligible patients with intermediate/high-risk SMM were randomized (1:1:1) to 3 intravenous (IV) daratumumab 16 mg/kg dosing schedules: long-intense, intermediate, and short-intense. 🛣️
•Long-intense: Weekly (cycle 1), WOQ (cycles 2-3), every 4 weeks (cycles 4-7), q8 weeks (cycles 8-20), with an optional extension phase of q8 weeks (SC) or IV daratumumab
•Intermediate: Weekly (cycle 1), then q8 weeks (cycles 2-20), with an optional extension phase of q8 weeks SC or IV daratumumab.
•Short-intense: Weekly for cycle 1 only

#USMIRC #MedEd #MedTwitter @OncoAlert @USMIRCNEWS #mmsm #myeloma #سرطان_الدم #المايلوما

MGCS: Monoclonal Gammopathy of clinical significance #mmsm #myeloma #MedEd #MedTwitter 🧵 #USMIRC @USMIRCNEWS Many differential diagnosis; mostly dependent on clinical diagnosis:
- Schintzler’s Syndrome
- Scleromyxedema
- TEMPI syndrome
- Cryoglobunemia
- NXG
- Clarkson disease

#mmsm #myeloma #MedEd #MedTwitter #USMIRC @USMIRCNEWS

1/Treatment of Myeloma:
- Transplant Eligible: (HR/SR)Dara/RVd
- Ineligible SR (DRd preferred)
Ineligible HR (VRd)
- Maintenance SR: lenalidomide
- Maintenance HR: VR (less evidence)
- 1st Relapse (HR/SR)Dara based therapy
- post triple RRMM: CAR-T then BCMA TCE then GPRC5D
#mmsm #myeloma #MedTwitter #MedEd #USMIRC @USMIRCNEWS @OncoAlert 2/Although 1q is considered as a High risk I still treat it as standard risk till I see more studies to show the impact of treatment on the outcomes!
- Regarding EMD (soft tissue) they are considered HR and treated within that group #mmsm #myeloma #MedTwitter #MedEd #USMIRC @USMIRCNEWS @OncoAlert

Hematology and Medical Oncology conference/ Kansas: Updates from ASCO 2023 #mmsm #myeloma #MedTwitter #MedEd #USMIRC Relapse myeloma still a challenge! 3 classes (IMiDs, PI and CD38 MoA) played a role to improve survival & we are looking to see BCMA Directed therapy added





BCMA CAR-T based on 2 RCT showed improved PFS compared to SOC and that is enough for me to change SOC to either Ide-Cel/Cilta-Cel #mmsm #myeloma #MedTwitter #MedEd #USMIRC

Flame Cells: These are plasma cells with vermillion-staining glycogen-rich overstuffed fibrils. Although these cytoplasmic features are suggestive of neoplastic plasma cells, can also be found in reactive cells. imagebank.hematology.org/image/3230/fla… #mmsm #myeloma #MedTwitter #USMIRC #MedEd Mott cell is a plasma cell characterized by an accumulation of multiple Russell bodies, globular cytoplasmic inclusions composed of immunoglobulin imagebank.hematology.org/image/61837/mo… #mmsm #myeloma #MedTwitter #MedEd #USMIRC