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

In this episode, we discussed the diagnosis and management of polycythemia vera with Dr. Aaron T. Gerds. Here are the shownotes with the key studies discussed: 

1.     MIPS PV scoring system

https://pubmed.ncbi.nlm.nih.gov/31945802/

2.     REVEAL study

https://ashpublications.org/blood/article/143/16/1646/506717/Association-between-elevated-white-blood-cell

3.     MAJIC PV study

https://ascopubs.org/doi/10.1200/JCO.22.01935?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

4.     Cyto-PV Study

https://www.nejm.org/doi/full/10.1056/NEJMoa1208500

5.     PROUD-PV and CONTINUATION-PV trials

https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(19)30236-4/abstract

6.     RESPONSE clinical trial

https://www.nejm.org/doi/full/10.1056/NEJMoa1409002

7.     Rusferitide in PV

https://www.nejm.org/doi/10.1056/NEJMoa2308809?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

In this episode, we reviewed the hottest updates in lymphoma from ASCO and EHA 2024, held in Chicago and Madrid respectively, with Dr. Gloria Iacoboni, a haematologist from University Hospital Vall d'Hebron, in Barcelona, Spain. Here are the key abstracts we discussed: 

1.      STARGLO: Glofit-GEMOX vs R-GEMOX in relapsed/refractory DLBCL

https://library.ehaweb.org/eha/2024/eha2024-congress/4136516

2.     Epco-Pola-R-CHP for 1st line DLBCL (EPCORE NHL-5 study):

https://library.ehaweb.org/eha/2024/eha2024-congress/422343

3.     3-year follow-up of TRANSFORM (Liso-Cel vs CITàASCT in R/R DLBCL): https://meetings.asco.org/abstracts-presentations/232740

4.     ECHO RCT: Acalabrutinib-BR vs Placebo-BR in previously untreated elderly MCL: https://library.ehaweb.org/eha/2024/eha2024-congress/4136515

5.     HD21: escBEACOPP vs BrECADD in 1st line classical HL: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01315-1/fulltext

6.     Combination pirtobrutinib, venetoclax, and obinutuzumab in 1st line CLL: https://library.ehaweb.org/eha/2024/eha2024-congress/422268

7.      Single-agent epcoritamab in Richter’s transformation: EPCORE CLL-1: https://library.ehaweb.org/eha/2024/eha2024-congress/422267

In this episode, we dive into updates in Minimal Residual Disease (MRD) in multiple myeloma, along with the FDA ODAC meeting in April 2024 to decide on MRD as a surrogate endpoint for accelerated approval. Our guests are Dr. Benjamin Derman and Dr. Manni Mohyuddin. Here are the key papers we discussed:

1.      Recording of FDA ODAC meeting: https://www.youtube.com/watch?v=pooME9gMaL0

2.     EVIDENCE meta-analysis on individual-level and trial-level correlation between MRD and PFS/OS in multiple myeloma: https://pubmed.ncbi.nlm.nih.gov/38768337/

3.     Predictors of un-sustained MRD-negativity in multiple myeloma: 

a)     Secondary analysis of FORTE trial: https://pubmed.ncbi.nlm.nih.gov/38048557/

b)     Secondary analysis of GEM2012MENOS65 and GEM2014MAIN trials: https://pubmed.ncbi.nlm.nih.gov/38048552/

4.     Kinetics of MRD resurgence and subsequent relapse in multiple myeloma: https://pubmed.ncbi.nlm.nih.gov/34807986/

5.     MRD2STOP trial (MRD-guided maintenance discontinuation): https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.106

6.     MRD-guided maintenance discontinuation in myeloma (Secondary analysis of GEM2012MENOS65 trial): https://pubmed.ncbi.nlm.nih.gov/37506339/

In this episode, we discuss updates in primary myelofibrosis with Dr. Ayalew Tefferi from the Mayo Clinic. 
The key studies and trials discussed are as follows:

·       GIPSS: Genetically inspired prognostic scoring system that is exclusively based on genetic markers.

§  https://www.nature.com/articles/s41375-018-0107-z

·       MIPSS70+ Version 2.0: Mutation and Karyotype-Enhanced International Prognostic Scoring System for Primary Myelofibrosis

§  https://ascopubs.org/doi/10.1200/JCO.2018.78.9867?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

·       TRANSFORM-1: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, International Phase 3 Study of Navitoclax in Combination with Ruxolitinib Versus Ruxolitinib Plus Placebo in Patients with Untreated Myelofibrosis

§  https://ashpublications.org/blood/article/142/Supplement%201/620/502738/Transform-1-A-Randomized-Double-Blind-Placebo

·       MANIFEST-2: Pelabresib in Combination with Ruxolitinib for Janus Kinase Inhibitor Treatment-Naïve Patients with Myelofibrosis: Results of the MANIFEST-2 Randomized, Double-Blind, Phase 3 Study

§  https://ashpublications.org/blood/article/142/Supplement%201/628/502728/Pelabresib-in-Combination-with-Ruxolitinib-for

·       XPORT-MF-034: Selinexor Plus Ruxolitinib in JAK Inhibitor (JAKi)-Naïve Patients with Myelofibrosis: Long Term Follow up from XPORT-MF-034 Suggestive of Disease Modification

In this episode, we dive into the data on maintenance therapy in multiple myeloma with Dr. Hira Mian and Dr. Manni Mohyuddin. Here are the key studies we discussed:

1. Meta-analysis of individual patient-level data from CALGB, IFM, and Italian maintenance RCTs (lenalidomide vs placebo or observation): 

https://pubmed.ncbi.nlm.nih.gov/28742454/

2. Myeloma XI RCT (lenalidomide vs observation): https://pubmed.ncbi.nlm.nih.gov/30559051/

3. Outcomes of lenalidomide maintenance stratified by cytogenetic subgroups (Secondary analysis of Myeloma XI): https://pubmed.ncbi.nlm.nih.gov/36564045/

4. Canadian real-world data on lenalidomide maintenance: https://pubmed.ncbi.nlm.nih.gov/33054120/

5. FORTE trial (Carfilzomib-Lenalidomide vs Lenalidomide): https://pubmed.ncbi.nlm.nih.gov/34774221/

6. ATLAS trial (Carfilzomib-Lenalidomide-Dexamethasone vs Lenalidomide): https://pubmed.ncbi.nlm.nih.gov/36642080/

7. Differential censoring and potential impact on PFS in ATLAS trial: https://pubmed.ncbi.nlm.nih.gov/37433885/

8. GEM2014 (Ixazomib-Lenalidomide-Dexamethasone vs Lenalidomide-Dexamethasone): https://ashpublications.org/blood/article-abstract/142/18/1518/497188

9. MASTER trial (MRD-guided treatment de-escalation): https://pubmed.ncbi.nlm.nih.gov/37776872/

10. Outcomes after MRD-guided treatment discontinuation (Secondary analysis of GEM2014MAIN trial): https://pubmed.ncbi.nlm.nih.gov/37506339/

In this episode, we discuss the diagnosis and management of Essential Thrombocythemia with Dr. Raajit Rampal. Here are the shownotes:
1.     IPSET (revised) system, risk categories are defined by the presence of a prior thrombosis, age, and JAK2 mutation status:

·        Very low risk: No prior thrombosis, age ≤60 years, JAK2-unmutated

·        Low risk: No prior thrombosis, age ≤60 years, JAK2-mutated

·        Intermediate risk: No thrombosis, age >60 years, JAK2-unmutated

·        High risk: History of thrombosis (any age/genotype), or age >60 years with JAK2 mutation

https://ashpublications.org/blood/article/120/26/5128/30914/Development-and-validation-of-an-International

2.    The MIPSS-ET provides points for:

·        Age > 60 years (3 points)

·        Adverse mutation (SF3B1/SRSF2/U2AF1/TP53) (2 points)

·        Male sex (1 point)

·        White blood cell count ≥11 × 10^9/L (1 point)

·        https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.16380?sid=nlm%3Apubmed

3.    Aspirin

o   Is there a benefit of twice-daily aspirin dosing, especially in high-risk or JAK2-mutant disease?

https://ashpublications.org/blood/article/136/2/171/454293/A-randomized-double-blind-trial-of-3-aspirin

4.     Cytoreduction in High-risk ET
 

Hydroxyurea: https://www.nejm.org/doi/full/10.1056/NEJM199504273321704

Pegylated interferon alfa

MPD-RC 112 Mascarenhas J et al. A randomized phase 3 trial of interferon- α vs hydroxyurea in polycythemia vera and essential thrombocythemia. Blood . 2022) 

https://ashpublications.org/blood/article/139/19/2931/483404/A-randomized-phase-3-trial-of-interferon-vs

Anagrelide in ET

https://ashpublications.org/blood/article/121/10/1720/31186/Anagrelide-compared-with-hydroxyurea-in-WHO

5.    Ruxolitinib  

In a randomized study phase 2 study (MAJIC-ET), ruxolitinib treatment did not deliver better rates of hematological response than best-available therapy, although symptoms did improve. 

·        MAJIC-ET study which is a randomized phase 2 trial 

·        ET patients resistant/intolerant to HU were randomized to receive RUX or standard treatment (HU 71%, anagrelide 48%, IFN 40%). The primary study outcome was CR, defined by normal platelet and white cell counts and normal spleen size.  

·        At 1 year, response was achieved in 46% of patients in the RUX group and in 44% in the standard arm, without statistically significant difference between the two groups.  

·        In addition, no difference was observed in the rates of thrombosis, hemorrhage, and disease transformation after 2 years of follow-up.  

·        MRs were also uncommon. RUX was superior, however, in symptom control. 

https://ashpublications.org/blood/article/130/17/1889/36509/Ruxolitinib-vs-best-available-therapy-for-ET