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

In this episode, we talked about overall survival data from CARTITUDE-4 and KarMMa-3 that was presented at FDA ODAC meeting with Dr. Samer Al Hadidi from University of Arkansas Myeloma Center.

RCTs of BCMA CAR T-cell Therapy in Early Relapsed Multiple Myeloma:

a) KarMMa-3 (ide-cel): https://pubmed.ncbi.nlm.nih.gov/36762851/

b) CARTITUDE-4 (cilta-cel): https://pubmed.ncbi.nlm.nih.gov/37272512/

FDA ODAC on overall survival data from KarMMa-3 and CARTITUDE-4:
https://www.youtube.com/watch?v=VSjdGeeXb40