#mmsm
How to counsel patients about Cilta Cel using the data from
CARTITUDE-4 and FDA ODAC meeting for earlier use

With data of Cilta cel and Ide cel, assuming having access to both for a given patient, I will personally chose Cilta cel (I explained this before)

🧵 In the first ~6 months after we plan to give you Cilta-cel, you have one out of 12 (8%) chances of dying either of progressive disease or adverse event to Cilta cel, this will depend on the bridging therapy we will use and your response to it (planning is important to ⬇️risk)

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GRIFFIN trial @TheLancetHaem #mmsm

➡️

✅Phase II trial of Dara-RVd vs. RVd
✅Final analysis after all pts had completed at least 1 year of follow-up after end of study ttt, had died, or withdrew from study participation.

Some learning points

🧵 thelancet.com/journals/lanha…
Primary endpoint of the study

➡️stringent complete response rate by end of post-HSCT consolidation
➡️Very important portion of the study 👇
➡️Assumption is 15% difference between Dara-RVd vs. RVd.

Note that statistical significance can be ascertained for 1ry endpoint

Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma | @NEJM #mmsm

➡️

Quick initial look

🧵 www-nejm-org.libproxy.uams.edu/doi/full/10.10…
Mezigdomide was previously known as CC-92480

✅ modulator of E3 ubiquitin ligase complex containing cereblon
✅ binds to cereblon and subsequently induces proteasome-mediated degradation of certain transcription factors➡️ activation of T-cells

#mmsm
Given the approval of talquetamab and AEs specific for this agent, here I provide some counseling tips and maneuvers to help lessen special AEs

✅Dose: 0.8 mg/kg SC every 2 wks: my preferred dosing

✅About 3 out 4 pts had a response per FDA package insert (n=87 pts)

🧵 #mmsm
🛑dysgeusia: unpleasant or altered taste sensation
🛑No Grade III/IV for this condition

G I: Altered taste but no change in diet
G II: Altered taste with change in diet (e.g., oral supplements); noxious or unpleasant taste; loss of taste

Absence of GIII/IV≠don't exist

Check out our correspondence for the real world data on the use of ide cel #mmsm @JCO_ASCO @ASCO @UAMSMyeloma @uamscancer

Intent Matters: Real-World Applicability of ide-cel Usage in the United States

➡️ascopubs.org/doi/10.1200/JC…

Led by @rajshekharucms @columbiacancer

🧵 ✅Violation of intent to treat principle

🛑17 of 196 (~9%) of patients who did not proceed to CAR T-cell infusion because of either disease progression/death (n = 12) or manufacturing failure (n = 5) were excluded from the final efficacy analysis👇

To understand how problematic some of smoldering myeloma trials are, look at the primary endpoint of a single arm study that is currently recruiting👇#mmsm
🛑using IMWG response criteria for multiple myeloma in smoldering myeloma is an inaccurate assumption 🧵 ➡️What is a response definition per 1ry endpoint?
All of:
1️⃣Disappearance of original monoclonal protein from blood and urine
2️⃣<5% plasma cells in bone marrow
3️⃣No increase in size or number of lytic bone lesions
4️⃣Disappearance of soft tissue plasmacytomas

#mmsm How do I treat smoldering myeloma?

Observation

How do I treat “high risk” smoldering myeloma?

Observation

Why don’t I enroll on most clinical trials of smoldering myeloma?

Because they assume that treatment (active control arm) is beneficial

🧵 In clinic, my consultation for smoldering myeloma takes a long time to go over details.

Patient must have completed comprehensive workup including advanced imaging

I yet to have a patient telling me they want a treatment after discussion

Patients appreciate uncertainty

Why peripheral neuropathy incidence is lower and cardiac toxicity is higher with carfilzomib when compared to bortezomib in multiple myeloma?

#mmsm
🧵 Peripheral neuropathy with proteosome inhibition:

❓likely caused by inhibition of a serine protease that is critical for neuronal cell survival called HtrA2/Omi

✅ carfilzomib has lower levels off-target protease inhibition (including activity at HtrA2/Omi protease)

Blood smears @ASH_hematology 🧵Heme boards
🩸Malignant Hematopoietic Neoplasms🩸
#mmsm #lymsm #leusm #bmtsm
1⃣ classic Hodgkin's lymphoma
🩸Reed-Sternberg cell👇
🩸Most common: Nodular sclerosis 👇(fibrosis)
🩸Usually:CD30+, CD15+, weak PAX5 +. CD20-, CD45-
🩸9p24.1 alteration Blood smears @ASH_hematology 🧵Heme boards
🩸Malignant Hematopoietic Neoplasms🩸
#mmsm #lymsm #leusm #bmtsm
2⃣ Nodular lymphocyte-predominant Hodgkin lymphoma
🩸popcorn cell (from germinal center B-cell)👇
🩸CD20+ (different than cHL),Rituxan used in ttt
🩸can transform(DLBCL)

#MedTwitter #HemeBoards @HemOncFellows
🧵Summary of erythrocytes inclusion bodies:

1️⃣Howell-Jolly body
➡️composition: DNA
🔬associations: splenectomy, hyposplenism, megaloblastic anemia, hemolytic anemia, sickle cell disease 2️⃣Basophilic stippling
➡️composition: RNA
🔬associations: lead intoxication, thalassemia, abnormal heme synthesis

#mmsm Hematologica published 3 articles for sub-group analysis for Isatuximab recently:
1-IKEMA pts with renal failure-Full article
2- ICARIA-MM elderly pt-letter to editor
3-IKEMA+ICARIA-MM: 1q-letter to editor
🛑All used 1-2 medical writers
Was this all the story ? 🧵 Same medical writers helped in a review of key subgroup analysis of ICARIA-MM 👇

Also in doing another subgroup analysis in high risk cytogenetics

#ASH21 Oral abstract:Ciltacabtagene Autoleucel for Triple-Class Exposed MM:Adjusted Comparisons of CARTITUDE-1 Patient Outcomes Versus Therapies from Real-World Clinical Practice from the LocoMMotion Prospective Study #mmsm 🧵
➡️ash.confex.com/ash/2021/webpr…
🛑some important issues👇 #ASH21 #mmsm
➡️Cilta Cel is effective in difficult to ttt pts, this is not the aim of the discussion
➡️In this abstract,authors compared a prospectively matched triple class ref MM pts who received diff ttt vs Cilta cel
➡️ what did they find? 👇 (Cilta Cel better) but wait🛑

Analyzing this study of defibrotide in VOD after transplant from Spain @amarkelkar @AkshaySharmaMD @hmgcoa2
➡️Link:tandfonline.com/doi/full/10.10… (accepted, not final)
➡️ Price data from Spain with €2019
➡️ FDA approved (March 30, 2016): fda.gov/drugs/resource… ➡️ VOD (~15% ,all types): a bad complication with high mortality (severe type, historically >80%)
➡️ Diagnosis &grading(see tables👇) (nature.com/articles/bmt20…)
➡️Authors question: is defibrotide cost-effective using price input from Spain (note this is likely different from US)

Summary of cytoplasm/nucleus changes in leukocytes:
1️⃣ Hyposegmentation of neutrophils(peanut shaped, bilobed,or non-segmented nucleus with coarse chromatin)
🔬associations: Pelger–Huët anomaly(inherited) or pseudo-Pelger–Huët anomaly(acquired)

#MedTwitter @ASH_hematology #Heme ➡️Pelger–Huët anomaly(inherited):affect majority of granulocytes: autosomal dominant- mutations in the lamin B receptor gene
➡️Pseudo-Pelger–Huët anomaly(acquired): <50% of granulocytes: usually occurs with other morphological changes of malignancy: can see in MPNs or MDS
#Heme