Blood Cancer Talks

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

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

In this episode, we discuss mentorship and career development as a clinician-investigator with Dr. Ayalew Tefferi from the Mayo Clinic. 

In this episode we discuss the management of newly diagnosed AL amyloidosis with Dr. Angela Dispenzieri from the Mayo Clinic. 

Here are the key articles discussed:

1.      Optimal use of tissue biopsy in AL amyloidosis: https://pubmed.ncbi.nlm.nih.gov/28271734/

2.     Mayo 2004 staging:  https://pubmed.ncbi.nlm.nih.gov/15365071/

3.     Mayo 2012 staging: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3675680/

4.     Renal staging: https://pubmed.ncbi.nlm.nih.gov/25115890/

5.     Hematologic and cardiac response criteria in AL amyloidosis: https://pubmed.ncbi.nlm.nih.gov/23091105/

6.     ANDROMEDA Trial: Dara-VCD vs VCD in newly diagnosed AL amyloidosis: https://pubmed.ncbi.nlm.nih.gov/34192431/

7.      How I Treat AL Amyloidosis: https://pubmed.ncbi.nlm.nih.gov/34517412/

8.     Venetoclax in AL amyloidosis (largest retrospective study till date): 

https://pubmed.ncbi.nlm.nih.gov/33431806/

In this episode, we discuss top abstracts in the myeloid space from the American Society of Hematology 2023 meeting with Dr. Anand Patel. 
Here are the abstracts that were discussed:

1. 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://ash.confex.com/ash/2023/webprogram/Paper173509.html

2. 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://ash.confex.com/ash/2023/webprogram/Paper179141.html

3. Venetoclax + Decitabine vs 7+3 in AML

https://ashpublications.org/blood/article/142/Supplement%201/970/503790/Comparing-the-Efficacy-and-Safety-of-Venetoclax

4. FILO study: Acute Myeloid Leukemia Patients Who Stopped Venetoclax or/and Azacytidine for Other Reasons Than Progression Have a Prolonged Treatment Free Remission and Overall Survival. 

https://ash.confex.com/ash/2023/webprogram/Paper185437.html 

5. AUGMENT-101: Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemia: Topline Efficacy and Safety Results

https://ash.confex.com/ash/2023/webprogram/Paper172422.html

6. VEN+HMA in HR MDS: Safety, Efficacy, and Patient-Reported Outcomes of Venetoclax in Combination with Azacitidine for the Treatment of Patients with Higher-Risk Myelodysplastic Syndrome: A Phase 1b Study

https://ash.confex.com/ash/2020/webprogram/Paper139492.html

In this episode, we talk about GVHD prophylaxis, including recent data on post-transplant cyclophosphamide and abatacept with Dr. Shernan Holtan from the University of Minnesota. 

Here are the key trials we discussed:

1. BMT CTN 1203 trial: Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of GVHD in allogeneic transplantation.

https://pubmed.ncbi.nlm.nih.gov/30824040/

2. BMT CTN 1703 study: Post-Transplantation Cyclophosphamide-Based GVHD prophylaxis 

https://pubmed.ncbi.nlm.nih.gov/37342922/

3. Patient-Reported Outcomes of BMT CTN 1703

https://ash.confex.com/ash/2023/webprogram/Paper187859.html

4. Phase II Study of Myeloablative 7-8/8-Matched Allotransplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil

https://pubmed.ncbi.nlm.nih.gov/37311510/

5. BMT CTN 1301 trial: Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies

https://pubmed.ncbi.nlm.nih.gov/34855460/

6. Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD (ABA2)

https://pubmed.ncbi.nlm.nih.gov/33449816/

7. Aurora Kinase a Inhibition for Gvhd and Relapse Prevention after Allogeneic HCT: Phase I Trial in Combination with Ptcy/Sirolimus

https://ash.confex.com/ash/2023/webprogram/Paper181292.html

In this episode, we discuss the key abstracts in myeloma and related plasma cell disorders at ASH23 with Dr. Benjamin Derman. Here are the abstracts discussed in this episode: 

First, we will focus on a few abstracts in precursor states, MGUS. 

1.      New diagnostic criteria for light chain MGUS (IStopMM): 

             https://ash.confex.com/ash/2023/webprogram/Paper188547.html

             https://ash.confex.com/ash/2023/webprogram/Paper182661.html

2.     PERSEUS Trial-Dara-VRD vs VRD in newly diagnosed transplant-eligible myeloma: 

https://ash.confex.com/ash/2023/webprogram/Paper191911.html

3.     ISKIA trial: Isa-KRD vs KRD in newly diagnosed transplant-eligible myeloma:

 https://ash.confex.com/ash/2023/webprogram/Paper177546.html

4.     Phase 1/2 study for Daratumumab-Venetoclax-Dexamethasone in early relapsed t(11;14) myeloma:

https://ash.confex.com/ash/2023/webprogram/Paper180766.html

5.     GMMG Relapse Trial (Long-term follow-up data from randomized controlled trial of salvage transplant in myeloma)

 
https://ash.confex.com/ash/2023/webprogram/Paper178835.html

6.     Overall survival results of KarMMa-3 trial

https://ash.confex.com/ash/2023/webprogram/Paper178933.html

7.      GEM2017FIT Trial: Dara-KRd vs KRd vs VMP-RD in non-transplant eligible patients:

https://ash.confex.com/ash/2023/webprogram/Paper179866.html

In this episode, we review the hottest updates in lymphoma from the American Society of Hematology 2023 meeting with Dr Toby Eyre, a consultant haematologist at the University of Oxford in the UK.

Here are the abstracts that were discussed:

Mantle Cell Lymphoma

1. BOVen trial-A Multicenter Phase 2 Trial of Zanubrutinib, Obinutuzumab, and Venetoclax in Patients with Treatment-Naïve, TP53-Mutant Mantle Cell Lymphoma

https://ash.confex.com/ash/2023/webprogram/Paper180069.html

2. SYMPATICO Trial: Ibrutinib Combined with Venetoclax in Patients with Relapsed/Refractory Mantle Cell Lymphoma (Late Breaking Abstract)

 https://ash.confex.com/ash/2023/webprogram/Paper191921.html

Chronic Lymphocytic Leukemia

1. FLAIR trial: Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease

Link for simultaneous NEJM publication: https://www.nejm.org/doi/10.1056/NEJMoa2310063

2. Ibrutinib retreatment in Phase 2 CAPTIVATE study:

https://ash.confex.com/ash/2023/webprogram/Paper187128.html

Hodgkin Lymphoma
 

1. S1826 outcomes in older adults: 

https://ash.confex.com/ash/2023/webprogram/Paper180114.html

Diffuse Large B-cell Lymphoma

1. Smart STOP study: Lenalidomide, Tafasitamab, Rituximab, and Acalabrutinib Alone and with Combination Chemotherapy for the Treatment of Newly Diagnosed Diffuse Large B-Cell Lymphoma

https://ash.confex.com/ash/2023/webprogram/Paper180381.html

2. Mosunetuzumab and Polatuzumab Vedotin Demonstrates Preliminary Efficacy in Elderly Unfit/Frail Patients with Previously Untreated Diffuse Large B-Cell Lymphoma

https://ash.confex.com/ash/2023/webprogram/Paper177588.html