In this episode, we explore the emerging entity of CAR Transgenic T-cell Lymphoproliferative Neoplasms (CTTLN), a rare but important complication of CAR T-cell therapy. Dr. Piers Blombery from Peter MacCallum Cancer Center joins us to dissect two cases from the CARTITUDE-4 trial where patients developed T-cell lymphomas expressing the chimeric antigen receptor following cilta-cel treatment for multiple myeloma. As a bonus, we also briefly discussed Dr. Blombery’s paper on menin inhibitors in UBTF tandem duplicated AML. Here are the papers we discussed: 

1. CTTLN cases from CARTITUDE-4: https://pubmed.ncbi.nlm.nih.gov/39938094/

2. CTTLN case from MSKCC with insertional mutagenesis: https://pubmed.ncbi.nlm.nih.gov/39908432/

3. Other CTTLN cases in myeloma:
https://pubmed.ncbi.nlm.nih.gov/38865661/
https://pmc.ncbi.nlm.nih.gov/articles/PMC8417502/

4. Response and resistance to menin inhibitors in UBTF tandem duplication AML: https://pubmed.ncbi.nlm.nih.gov/38924737/

In this episode, we delve into the key clinically relevant abstracts in leukemia and myeloid neoplasms with Dr. Jayastu Senapati from the MD Anderson Cancer Center. Here are the links to the abstracts we discussed: 

Older AML: Ven+HMA vs 7+3

Abstract 450: https://ash.confex.com/ash/2024/webprogram/Paper210320.html

Abstract 971: https://ash.confex.com/ash/2024/webprogram/Paper202801.html

Abstract 969: https://ash.confex.com/ash/2024/webprogram/Paper199267.html

Venetoclax resistance mechanisms

https://pubmed.ncbi.nlm.nih.gov/39478230/

FLAG-GO vs FLAG-IDA 

https://ashpublications.org/blood/article/144/Supplement%201/1513/532742/Gemtuzumab-Ozogamicin-Added-to-Fludarabine

 CPX-351: 

Abstract 55: https://ash.confex.com/ash/2024/webprogram/Paper207094.html

Abstract 60: https://ash.confex.com/ash/2024/webprogram/Paper200413.html

Menin Inhibitors 

Abstract 211 https://ash.confex.com/ash/2024/webprogram/Paper194384.html

Abstract 212 https://ash.confex.com/ash/2024/webprogram/Paper207106.html

Abstract 213 https://ash.confex.com/ash/2024/webprogram/Paper194827.html

Abstracts 214 https://ash.confex.com/ash/2024/webprogram/Paper198218.html

Abstract 215 https://ash.confex.com/ash/2024/webprogram/Paper198218.html

Abstract 216 https://ash.confex.com/ash/2024/webprogram/Paper204375.html

FLT3 inhibitors
Abstract 221: https://ash.confex.com/ash/2024/webprogram/Paper201595.html

MDS

 Abstract 349: https://ash.confex.com/ash/2024/webprogram/Paper194510.html

ATRA in MDS:  

https://ash.confex.com/ash/2024/webprogram/Paper200433.html 

In this episode, we discuss the management of CML with Dr. Hagop Kantarjian from MD Anderson Cancer Center. Here are the key articles we discussed: 

1. ASC4FIRST RCT: Asciminib in newly diagnosed CML. 

https://pubmed.ncbi.nlm.nih.gov/38820078/

2. 5-year follow-up of ENESTnd RCT (nilotinib): 

https://pubmed.ncbi.nlm.nih.gov/26837842/

3. 10-year follow-up of ENESTnd RCT (nilotinib): 

https://pubmed.ncbi.nlm.nih.gov/33414482/

4. 10-year follow-up of CML-IV RCT (imatinib): 

https://pubmed.ncbi.nlm.nih.gov/25676422/

5. MD Anderson data on low-dose dasatinib (50 mg): 

https://pubmed.ncbi.nlm.nih.gov/36054032/

https://pubmed.ncbi.nlm.nih.gov/31553487/

6. CML: 2025 update on diagnosis, therapy, and monitoring: 

https://pubmed.ncbi.nlm.nih.gov/39093014/

In this episode, we dive into the hottest updates in myeloma and amyloidosis at ASH 2024 annual meeting with Dr. Rakesh Popat. Here are the abstracts we discussed:

1. AQUILA Trial in High-Risk SMM

• Overview of the AQUILA trial testing single-agent daratumumab for high-risk smoldering multiple myeloma (HR-SMM) versus active monitoring.
•  Discussion on patient characteristics, primary endpoints, and results showing significant progression-free survival (PFS) benefit with Dara.
•  Insights into modes of progression, adequacy of active surveillance, and post-protocol therapy in control arm.
•  Read the abstract.
•  Read the simultaneous publication at NEJM. 

2. Anito-Cel: New BCMA CAR T Therapy

•  Early data from the iMMagine-1 trial showing strong efficacy and a promising safety profile for Anito-Cel, a novel BCMA CAR T.
•  Discussion of its potential to rival cilta-cel while avoiding neurotoxicity concerns.
•  Read the abstract.

3. CARTITUDE-4 Update

•  Updates on MRD-negativity rates and survival outcomes for cilta-cel in relapsed myeloma, with significant benefits over standard care.
•  Read the abstract.

4. ANDROMEDA OS Data in AL Amyloidosis

•  Long-term data showing an overall survival (OS) benefit of Dara-VCd over VCd in AL amyloidosis.
•  Insights into cardiac responses and crossover impact.
•  Read the abstract.

5. OPTIMUM Trial in Ultra-High-Risk NDMM

• Five-year follow-up of a tailored approach for ultra-high-risk newly diagnosed myeloma patients with continuous therapy incorporating multiple active agents. 
• Subgroup outcomes highlighting both challenges and exceptional results.
•  Read the abstract

6. GMMG-HD7 Trial PFS Update

•  Phase 3 trial results on Isa-VRD vs. VRD induction and risk-adapted tandem ASCT.
•  Discussion on the role of CD38 in maintenance therapy.
•  Read the abstract
•  Read the simultaneous publication at JCO

7. Exciting New Drugs

•  Review of three innovative therapies: inobrodib, a BCMA-CD38 trispecific antibody, and cevostamab, a FcRH5-targeted bispecific antibody.
•  Expert insights into their efficacy and potential to reshape myeloma care.
•  Read the abstract

In this episode, we discussed the top abstracts in lymphoma and CLL presented at the ASH 2024 annual meeting in San Diego with Dr. David A Russler-Germain from Washington University. Here are the key abstracts we discussed: 

1. 3 RCTs in Mantle Cell Lymphoma: 

a) Update on TRIANGLE: https://ash.confex.com/ash/2024/webprogram/Paper200735.html

b) ENRICH Trial (Continuous Ibrutinib-Rituximab vs CIT [R-CHOP or BR]): https://ash.confex.com/ash/2024/webprogram/Paper199710.html

c) ECOG-ACRIN EA4151 Trial (Auto-HCT vs Rituximab maintenance alone in patients with undetectable MRD after induction): https://ash.confex.com/ash/2024/webprogram/Paper212973.html

2. DLBCL: 

a) Update on POLARIX Trial: https://ash.confex.com/ash/2024/webprogram/Paper197938.html

b) Predictive Value of Cell-of-Origin Subtype By Hans Algorithm in DLBCL Patients Receiving Polatuzumab Vedotin: https://ash.confex.com/ash/2024/webprogram/Paper202153.html

c) COALITION trial: https://ash.confex.com/ash/2024/webprogram/Paper204930.html

3. Follicular Lymphoma: 

a) Phase 3 inMIND trial (Tafasitamab + R2 vs Placebo + R2): https://ash.confex.com/ash/2024/webprogram/Paper212970.html

b) Loncastuximab tesirine with rituximab in patients with R/R FL: https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00345-4/abstract

4. CLL: 

a) AMPLIFY Trial (Fixed-Duration Acalabrutinib Plus Venetoclax with or without Obinutuzumab Versus Chemoimmunotherapy in 1st line CLL): https://ash.confex.com/ash/2024/webprogram/Paper200701.html

5. Hodgkin Lymphoma: 

a) Pembrolizumab Maintenance Instead of Auto-HCT for R/R HL: https://ash.confex.com/ash/2024/webprogram/Paper202537.html

In this episode, we discuss the comeback of belantamab mafadotin in multiple myeloma with Dr. Hang Quach, along with some other important abstracts presented at EHA/ASCO 2024. Here are the studies we discussed: 

1. DREAMM-7 RCT: Belantamab-Vd vs Daratumumab-Vd in relapsed MM. https://pubmed.ncbi.nlm.nih.gov/38828933/

2. DREAMM-8 RCT: Belantamab-Pd vs PVd in relapsed MM. https://pubmed.ncbi.nlm.nih.gov/38828951/

3. Long-term follow-up of CASSIOPEIA Trial: https://pubmed.ncbi.nlm.nih.gov/38889735/

4. Update on MRD data from PERSEUS Trial: https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7502

In this episode, we dive into the management of older adults with Hodgkin Lymphoma with Dr. Andrew Evens.
Here are the key articles we discussed:

1. Comparison of ABVD versus Stanford V in older Hodgkin Lymphoma patients: https://pmc.ncbi.nlm.nih.gov/articles/PMC3906856/

2. Outcome of older adults ECHELON-1: https://pubmed.ncbi.nlm.nih.gov/34162178/

3. Sequential BV-AVD in older adults with Hodgkin Lymphoma: https://pubmed.ncbi.nlm.nih.gov/30179569/

4. SWOG S1826 trial (Nivo-AVD vs AAVD in advanced stage classical HL): https://pubmed.ncbi.nlm.nih.gov/39413375/

5. S1826 outcomes in older adults: https://ash.confex.com/ash/2023/webprogram/Paper180114.html

6. Single-agent BV for older adults with Hodgkin: https://ashpublications.org/blood/article/142/Supplement%201/4435/503453

In this episode, we discuss the history of venetoclax in AML, along with key clinical trials that have shaped its current use in AML. Here are the trials discussed in this episode:
 

1. VIALE-A study: https://www.nejm.org/doi/full/10.1056/NEJMoa2012971

2. 10 day Decitabine plus venetoclax for ND AML https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(20)30210-6/abstract

3. Genetic Risk Stratification and Outcomes with AML treated with venetoclax and azacitidine https://ashpublications-org.proxy.library.vanderbilt.edu/blood/article/doi/10.1182/blood.2024024944/517355/Genetic-Risk-Stratification-and-Outcomes-Among

4. Genetic risk classification for adults with AML receiving less-intensive therapies: the 2024 ELN recommendations https://ashpublications-org.proxy.library.vanderbilt.edu/blood/article/doi/10.1182/blood.2024025409/517356/Genetic-risk-classification-for-adults-with-AML

5. AGILE study: Ivosidenib and azacitidine in IDH1-mutated AML https://www.nejm.org/doi/full/10.1056/NEJMoa2117344

6. MRD response and prognosis in treatment naïve AML with AZA/VEN https://ascopubs.org/doi/10.1200/JCO.21.01546?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

7. Monocytic subclone confer resistance to venetoclax-based therapy in patients with AML https://aacrjournals.org/cancerdiscovery/article/10/4/536/2403/Monocytic-Subclones-Confer-Resistance-to

8. VEN/DEC vs 7+3 https://ashpublications.org/blood/article/142/Supplement%201/970/503790/Comparing-the-Efficacy-and-Safety-of-Venetoclax

9. FILO study: Outcomes of AML  https://onlinelibrary.wiley.com/doi/10.1002/ajh.27417

10. Treatment-free remission after ceasing venetoclax-based therapy in patients with AML https://ashpublications-org.proxy.library.vanderbilt.edu/bloodadvances/article/6/13/3879/485175/Treatment-free-remission-after-ceasing-venetoclax

11. Targeting molecular MRD and low-blast relapse in AML with Venetoclax and LDAC (VALDAC) https://ascopubs-org.proxy.library.vanderbilt.edu/doi/10.1200/JCO.23.01599?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

12. INTERCEPT trial: https://ashpublications.org/blood/article/140/Supplement%201/3341/492722/ALLG-AMLM26-Phase-1B-2-Study-Investigating-Novel

In this episode, we discuss the management of newly diagnosed transplant in-eligible multiple myeloma with Dr. Timothy Schmidt, with a special focus on IMROZ and BENEFIT RCTs testing quadruplets in this space. 

Here are the key papers we discussed: 

1. MAIA trial (Daratumumab-Lenalidomide-Dexamethasone [DRd] vs Rd in newly diagnosed transplant ineligible myeloma): https://pubmed.ncbi.nlm.nih.gov/34655533/

2. S0777 trial (VRd vs Rd in newly diagnosed myeloma [transplant-ineligible or transplant-deferred]): https://pubmed.ncbi.nlm.nih.gov/32393732/

3. IMROZ trial (Isatuximab-VRd vs VRd in newly diagnosed transplant-ineligible myeloma): https://pubmed.ncbi.nlm.nih.gov/38832972/

4. IFM-2020/BENEFIT trial (Isatuximab-VRd vs Isatuximab-Rd in newly diagnosed transplant-ineligible myeloma): https://pubmed.ncbi.nlm.nih.gov/38830994/

5. GEM2017FIT trial (VMP-Rd vs KRd vs Dara-KRd in newly diagnosed transplant-ineligible myeloma): https://ashpublications.org/blood/article/142/Supplement%201/209/500199

In this episode, we discuss updates on low-risk MDS with Dr. Maximilian Stahl with a focus on imetelstat and luspatercept. 
Here are the trials we discussed: 
1. IWG 2019 response criteria

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042664/ 

2. MEDALIST trial: Luspatercept

https://www.nejm.org/doi/10.1056/NEJMoa1908892?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed 

3. COMMANDS trial : Luspatercept 

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00874-7/abstract

https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00203-5/abstract 

4. IMerge trial: Imetelstat 

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01724-5/abstract