WolverHeme Happy Hour (Bernard Marini, Anthony Perissinotti, et al.)

In this episode, Anthony, Bernie, and Lydia are joined by a former patient, Madeline B, to talk about her ALL treatment journey. Drawing inspiration from Taylor Swift's upcoming concert and heartfelt ballad ("All Too Well"), this episode tackles some of the unique challenges, emotions, and considerations that come with helping adolescents and young adults (AYA) with treatment for acute leukemia. This is a must-listen for anyone taking care of AYA patients!

Blinatumomab - it's Oprah's new favorite drug!

On this episode, Anthony and Bernie are joined by special guests Dr. Lydia Benitez and Dr. Patrick Burke to discuss the ECOG1910 trial of blinatumomab in adult ALL. Is this trial practice changing? Listen and find out!

• ECOG1910 Late-Breaking Abstract: https://ash.confex.com/ash/2022/webprogram/Paper171751.html 

Finally back from a much needed vacation, in this episode, Anthony and Bernie discuss some of the "OG" data and pharmacology behind key AML therapies. 

OMG! In this extra fun holiday episode, we are joined by lymphoma experts Tycel Phillips and Aaron Goodman to review the most impactful and controversial lymphoma abstracts from ASH! Stay tuned for a lively discussion!

Abstracts Discussed!

1. SYMPATICO (Ibrutinib + Ven in R/R MCL): https://ash.confex.com/ash/2023/webprogram/Paper191921.html
2. Nivo-AVD in elderly Hodgkin Lymphoma: https://ash.confex.com/ash/2023/webprogram/Paper180114.html
3. BOVEN - Zanubrutinib + Obi + Ven in TP53 mutant MCL: https://ash.confex.com/ash/2023/webprogram/Paper180069.html
4. CAR-T in CNS Lymphoma: https://ash.confex.com/ash/2023/webprogram/Paper174883.html (EBMT data), https://ash.confex.com/ash/2023/webprogram/Paper184345.html (Multicenter retrospective study)
5. Synthetic Control Arms: https://ash.confex.com/ash/2023/webprogram/Paper177708.html
6. POLARIX Subgroup Analysis (shout out to the Blood Cancer Talks crew!): https://x.com/Eddie_Cliff/status/1733901400822993257?s=20

In this episode, we are joined by Dr. Jill Lykon, Clinical Pharmacist Specialist in Hematology at the University of Miami, to discuss the use of IDH inhibitors in relapsed/refractory AML. How do we choose between IDH inhibitors? Is "Olu" the new standard IDH inhibitor in R/R AML, or just the name of a drunk snowman? What about ivosidenib? 

• Olutasidenib Phase I - Watts, et al. Lancet. 2023: https://pubmed.ncbi.nlm.nih.gov/36370742/
• Olutasidenib Phase II ASH Abstract: https://ash.confex.com/ash/2022/webprogram/Paper167330.html
• Ivosidenib Phase I escalation/expansion - Dinardo, et al. NEJM. 2018: https://pubmed.ncbi.nlm.nih.gov/29860938/
• Design of olutasidenib and other IDH inhibitors: https://pubmed.ncbi.nlm.nih.gov/31971798/ and https://pubmed.ncbi.nlm.nih.gov/36091829/
• Episode 5 of WolverHeme Happy Hour (for background on IDH Inhibitors and frontline data): https://open.spotify.com/episode/4eNXjuGEFFRWTFJF0zsuMw?si=9bd0ae0a488e44ba 

In this episode, Anthony and Bernie discuss the AML abstracts at ASH that we found most intriguing and controversial!

Abstracts:

• FILO - Stopping Aza/Ven: https://ash.confex.com/ash/2023/webprogram/Paper185437.html
• Revumenib Late Breaking Abstract: https://ash.confex.com/ash/2023/webprogram/Paper192042.html
• JNJ617 Menin Inhibitor Data: https://ash.confex.com/ash/2023/webprogram/Paper172422.html
• SAVE Trial (Revumenib + PO Dec/ven): https://ash.confex.com/ash/2023/webprogram/Paper182337.html
• Dec/Ven vs. 3+7 Randomized Phase II: https://ash.confex.com/ash/2023/webprogram/Paper181347.html
• NCRI AML18 RCT: https://ash.confex.com/ash/2023/webprogram/Paper185956.html
• Impact of NPM1+/FLT3+/MRD in AML17 and AML19: https://ash.confex.com/ash/2023/webprogram/Paper179033.html
• CBF and NPM1 MRD: https://ash.confex.com/ash/2023/webprogram/Paper184848.html
• Persistent MRD by PCR but Flow Negativity in CBF AML (Mast Cell Madness): https://ash.confex.com/ash/2023/webprogram/Paper180275.html
• MORPHO More MRD Analysis: https://ash.confex.com/ash/2023/webprogram/Paper177929.html

In the second portion of our two part-series on AML maintenance, Anthony and Bernie delve into the studies of post-transplant FLT3 inhibitor maintenance. We discuss the controversial MORPHO study of gilteritinib and whether these results will change practice!

• Sorafenib observational study: https://pubmed.ncbi.nlm.nih.gov/30809038/
• SORMAIN (sorafenib): https://pubmed.ncbi.nlm.nih.gov/32673171/
• Chinese Sorafenib Phase III: https://pubmed.ncbi.nlm.nih.gov/32791048/
• RADIUS (midostaurin): https://pubmed.ncbi.nlm.nih.gov/33288862/
• AMLSG 16-10 (midostaurin): https://pubmed.ncbi.nlm.nih.gov/30563875/
• MORPHO (EHA abstract): https://library.ehaweb.org/eha/2023/eha2023-congress/391322/faculty.presenters.bmt-ctn.1506.28morpho29.a.randomized.trial.of.the.flt3.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dmorpho

In this episode, Bernie and Anthony review the full history of APL treatment, in preparation for the upcoming plenary presentation of the APOLLO study THIS WEEKEND at EHA 2024!

How did we get to our current standard of care in APL? How and why did the PETHEMA, GIMEMA, UK MRC, and other cooperative group regimens evolve over time into what they are today?

And importantly, is the APOLLO control arm (no arsenic!), ok? Tune in to find out!

In this episode, Anthony and Bernie discuss the recently reported APOLLO trial in high-risk APL and debate whether this should represent the new standard of care in this population. We also review key practical considerations for the treatment of APL patients, including side effect management and treatment of APL in unique clinical scenarios.

APOLLO: https://library.ehaweb.org/eha/2024/eha2024-congress/422206/uwe.platzbecker.first.results.of.the.apollo.trial.a.randomized.phase.iii.study.html

In this episode, Anthony and Bernie are joined by Multiple Myeloma expert Dr. Manni Mohyuddin, to discuss the recent FDA approval updates of CAR-T in this disease state. We also discuss the hotly debated topic of MRD as a surrogate endpoint for accelerated approval in Myeloma.

Bernie Marini and Anthony Perissinotti discuss the following paper on whether or not event-free survival (EFS) is an appropriate surrogate endpoint for overall survival (OS) in AML:

Norsworthy KJ, et al. Response Rate, Event-Free Survival, and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia: US Food and Drug Administration Trial-Level and Patient-Level Analyses. J Clin Oncol. 2022 Mar 10;40(8):847-854. PMID: 34890212.

In this episode, we are joined by two lymphoma experts - Victoria Nachar, PharmD, BCOP and Tycel Phillips MD - to discuss the use of bispecific antibodies in Diffuse Large B-Cell Lymphoma (DLBCL)! Stay tuned for an exciting episode where we discuss the data, their possible role in therapy, and what questions and controversies remain.

Relevant Articles:

Review on Design of Bispecifics - https://pubmed.ncbi.nlm.nih.gov/25728220/

Epcoritamab - https://pubmed.ncbi.nlm.nih.gov/36548927/

Glofitamab - https://pubmed.ncbi.nlm.nih.gov/36507690/

Mosunetuzumab - https://pubmed.ncbi.nlm.nih.gov/34914545/

Odronextamab - https://pubmed.ncbi.nlm.nih.gov/35366963/

CRS and ICANS grading - https://pubmed.ncbi.nlm.nih.gov/30592986/

In this episode, we are joined by the legendary hematologist and rock star - Dr. Aaron Goodman - aka "Papa Heme"! We discuss which ASH abstracts might be practice changing and which simply don't make the cut. Stay tuned for an entertaining and very educational episode! 

In this episode, Bernie Marini and Anthony Perissinotti chat with special guest Charles Foucar, MD, a hematology specialist and expert in the field. We discuss the controversial FDA approval of ivosidenib in combination with azacitidine in newly diagnosed IDH1+ AML, based on the results of the AGILE study: https://www.nejm.org/doi/full/10.1056/NEJMoa2117344

In this episode released just in time for the holidays, Anthony and Bernie are joined by Tycel Phillips, MD to discuss the most exciting updates from ASH 2024 in lymphoma! Pour yourself a drink and have a listen!

Some selected abstracts:

• EA4151: https://ash.confex.com/ash/2024/webprogram/Paper212973.html
• Triangle Updates: https://ash.confex.com/ash/2024/webprogram/Paper200735.html , https://ash.confex.com/ash/2024/webprogram/Paper201441.html
• EA4181: https://ash.confex.com/ash/2024/webprogram/Paper194641.html
• ENRICH: https://ash.confex.com/ash/2024/webprogram/Paper199710.html
• inMIND: https://ash.confex.com/ash/2024/webprogram/Paper212970.html
• POLARIX Long-Term F/U: https://ash.confex.com/ash/2024/webprogram/Paper197938.html

In this episode, Tycel Phillips, MD joins Anthony and Bernie to discuss updates in Mantle Cell Lymphoma, including the TRIANGLE study and the recently published results of glofitamab in R/R MCL.

TRIANGLE: https://pubmed.ncbi.nlm.nih.gov/38705160/

Glofitamab: https://pubmed.ncbi.nlm.nih.gov/39365960/

AQUILA is a constellation shaped like an eagle, and also a hotly debated myeloma trial of daratumumab in smoldering multiple myeloma. In this episode, Bernie and Anthony are joined by myeloma expert Manni Mohyuddin to discuss the study's findings and whether or not they should change practice! Grab a drink and listen in for an exciting discussion.

Note: L'aquila is Italian for eagle!

AQUILA: Dimopoulos MA, et al. N Engl J Med. 2024 Dec 9. doi: 10.1056/NEJMoa2409029. Epub ahead of print. PMID: 39652675.

In part one of a two-part episode, Bernie Marini and Anthony Perissinotti take a journey through the history of acute lymphoblastic leukemia treatment throughout the decades and explain how we got to our current standard of care treatment of ALL patients. In part 2 we tackle the UKALL14 study evaluating the addition of rituximab to acute lymphoblastic leukemia therapy.

Some important historical articles that we reference:

• Nitrogen mustard therapy: https://pubmed.ncbi.nlm.nih.gov/20997191/
• Methotrexate/Aminopterin: https://www.nejm.org/doi/full/10.1056/nejm194806032382301
  • Vincristine: https://pubmed.ncbi.nlm.nih.gov/13627916/ and https://pubmed.ncbi.nlm.nih.gov/2085431/ and https://www.utpjournals.press/doi/pdf/10.3138/cbmh.17.1.155
• 6-MP: https://pubmed.ncbi.nlm.nih.gov/13105700/
• Total Therapy: https://pubmed.ncbi.nlm.nih.gov/5237796/ and https://pubmed.ncbi.nlm.nih.gov/5279904/
• BFM: https://pubmed.ncbi.nlm.nih.gov/320377/ and https://pubmed.ncbi.nlm.nih.gov/23700050/

This episode is dedicated to the late Don Pinkel (9/7/1927 - 3/9/2022), a pioneer in the treatment of childhood ALL. Read more about his legacy here: https://cancerletter.com/obituary/20220318_4/ and https://www.nature.com/articles/s41375-022-01562-9.pdf and https://www.smithsonianmag.com/innovation/childhood-leukemia-untreatable-dr-don-pinkel-st-jude-180959501/

In this episode, Anthony and Bernie are joined by two very special guests - Dr. Aaron "Papa Heme" Goodman and Dr. Manni "Myeloma Man" Mohyuddin - to discuss the most interesting myeloma abstracts at the upcoming 2023 ASH meeting! Will any of these change practice? Listen to find out!

Abstracts Discussed:

• https://ash.confex.com/ash/2023/webprogram/Paper188547.html
  
• https://ash.confex.com/ash/2023/webprogram/Paper181765.html
• https://ash.confex.com/ash/2023/webprogram/Paper177954.html
• https://ash.confex.com/ash/2023/webprogram/Paper191911.html
• https://ash.confex.com/ash/2023/webprogram/Paper179866.html
• https://ash.confex.com/ash/2023/webprogram/Paper177546.html
• https://ash.confex.com/ash/2023/webprogram/Paper178835.html
• Also check out Manni's excellent tweetorial on some of these key abstracts: https://x.com/ManniMD1/status/1726980328559133028?s=20

In this episode, Anthony and Bernie begin to recap some interesting studies presented at ASH, starting with a discussion the results of the "Dauno-Double" Trial. Should it change practice?

Dauno-Double Trial: https://ash.confex.com/ash/2022/webprogram/Paper157126.html

Dr. Todd Lee breaking down the non-inferiority numbers: https://twitter.com/DrToddLee/status/1600662377250586627?s=20&t=RdIhJJpMG-G_oPUSH2u2mw 

In this episode, Bernie Marini and Anthony Perissinotti are joined by two special guest hematology experts - Lydia Benitez, PharmD, BCOP, and Madeleine Ochs, PharmD, BCOP. Maddy and Lydia help us dive into the topic of Oncology Stewardship, including how we can incorporate Oncology Stewardship into practice to improve outcomes for patients. 

Learn more about Oncology Stewardship in AML patients in our hot off the press paper in Annals of Hematology, written by Maddy (first author), Lydia (senior author), and the rest of our leukemia team:

https://link.springer.com/article/10.1007/s00277-022-04872-1

In this episode, Anthony and Bernie review the most impactful and interesting ALL abstracts at the 2023 ASH Annual Meeting. We dive into the nelarabine abstracts, calaspargase (cal-peg), and the evolution of the treatment of Ph+ ALL!

Abstracts discussed:

• https://ash.confex.com/ash/2023/webprogram/Paper190141.html - COG AYA Outcomes (and silly nelarabine conclusions)
• https://ash.confex.com/ash/2023/webprogram/Paper177696.html - ATRIALL Nelarabine study
• https://ash.confex.com/ash/2023/webprogram/Paper179562.html - HyperCVAD + Nelarabine + PEG + venetoclax
• https://ash.confex.com/ash/2023/webprogram/Paper179192.html - ALL-TARGET Study in R/R T-ALL
• https://ash.confex.com/ash/2023/webprogram/Paper187694.html - Cal-PEG is toxic
• https://ash.confex.com/ash/2023/webprogram/Paper188064.html - Ponatinib + Blinatumomab
• https://ash.confex.com/ash/2023/webprogram/Paper187773.html - D-ALBA (Dasatinib + Blinatumomab)
• https://ash.confex.com/ash/2023/webprogram/Paper189632.html - GIMEMA (Dasatinib or Ponatinib + Blinatumomab)

In the first of a two part-series, Anthony and Bernie dive into the data surrounding maintenance therapies in AML. This episode focuses on maintenance therapy for patients ineligible for transplant, with a focus on oral azacitidine and the controversial QUAZAR study.

Key References:

• QUAZAR AML-001: https://pubmed.ncbi.nlm.nih.gov/33369355/
• QUAZAR Letter to the Editor: https://pubmed.ncbi.nlm.nih.gov/33789022/

• ASH Abstract Data on impact of # of Consolidation Cycles: https://ash.confex.com/ash/2020/webprogram/Paper138498.html
• Hovon 97 (Azacitidine SQ maintenance): https://pubmed.ncbi.nlm.nih.gov/30630862/

• Mayer, et al. NEJM. 1994. (CALGB HiDAC consolidation): https://pubmed.ncbi.nlm.nih.gov/8078551/
• Büchner, et al. JCO. 1985: https://pubmed.ncbi.nlm.nih.gov/3906048/

In this episode, Anthony and Bernie are joined by Dr. Aaron "Papa Heme" Goodman and Dr. Manni "Myeloma Man" Mohyuddin to discuss the most intriguing ASH 2024 abstracts! Should any of the research from ASH 2024 change your practice? Find out!

In this enlightening episode, Anthony and Bernie chat about FLT3+ AML with Dr. Dale Bixby, Clinical Professor and expert in leukemia at the University of Michigan. We use two clinical cases to take a deep dive into the biology and prognostic implications of FLT3+ AML, pitfalls and controversies of variant allele frequency and allelic ratio testing, and the data that informs the use of FLT3 inhibitors in AML. Watch out for some possibly heretical views!

REFERENCES

Schlenk and Dohner (Impact of AML prognostic markers)l: https://pubmed.ncbi.nlm.nih.gov/19468271/

RATIFY Trial: https://www.nejm.org/doi/full/10.1056/nejmoa1614359

QUANTUM-FIRST: https://library.ehaweb.org/eha/2022/eha2022-congress/356965/harry.erba.quizartinib.prolonged.survival.vs.placebo.plus.intensive.induction.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2233%2Amarker%3D1749%2Afeatured%3D17676

ODAC Review of Quantum-R (quizartinib): https://www.fda.gov/media/124896/download

ELN 2022: https://pubmed.ncbi.nlm.nih.gov/35797463/

WHO Myeloid 2022: https://pubmed.ncbi.nlm.nih.gov/35732831/

Sorafenib Maintenance (RCT China): https://pubmed.ncbi.nlm.nih.gov/32791048/

SorMAIN: https://pubmed.ncbi.nlm.nih.gov/32673171/

RADIUS (midostaurin maintenance): https://pubmed.ncbi.nlm.nih.gov/33288862/

LACEWING Trial: https://pubmed.ncbi.nlm.nih.gov/35917453/

HMA/Ven pooled FLT3: https://pubmed.ncbi.nlm.nih.gov/35063965/

Ven/Aza/Gilteritinib ASH 2022: https://ash.confex.com/ash/2022/webprogram/Paper157210.html

UK NCRI AML 17 Flt3 analysis: https://pubmed.ncbi.nlm.nih.gov/27268085/

In this episode, Bernie and Anthony do an in-depth dive into the pharmacology, toxicity management, and clinical conundrums with asparaginase therapy, including how and when to monitor asparaginase activity levels (per Papa Heme request!). For those who don't know (and maybe aren't as nerdy as we are), the title is a reference to the 1964 film Dr. Strangelove!

In this episode, Anthony and Bernie are joined once again by special guest and hematology expert, Dr. Dale Bixby, to discuss the recent publication of the QUANTUM-First study of quizartinib in newly diagnosed AML. Should this study change practice in FLT3-ITD+ AML? Have we made a "Quantum Leap" in the treatment of these patients? Listen for a fun-filled discussion of the data!

Notable References:

• QUANTUM-First Study: https://pubmed.ncbi.nlm.nih.gov/37116523/
• WolverHeme Episode 8 (Pulling the Goalie on FLT3 Inhibitor Use in AML): https://podcasters.spotify.com/pod/show/wolverheme/episodes/Episode-8-Pulling-the-Goalie-on-FLT3-Inhibitor-Use-in-AML---A-Discussion-with-Dr--Dale-Bixby-e1r6tqt/a-a8tthkc

Bernie Marini and Anthony Perissinotti discuss asparaginase, the data (or lack thereof) behind the FDA approval of Rylaze (Erwinia asparaginase), and concerning trends regarding switches between asparaginase products in clinical practice! 

In this episode, Bernie and Anthony are joined by two special guest expert hematologists:

Dr. David Russler-Germain

Dr. Tycel Phillips

We discuss recent updates in the treatment of upfront Classical Hodgkin Lymphoma, including whether the SWOG S1826 and HD21 trials change practice! Will it be a landslide victory for nivolumab? Is brentuximab fired?

Stay tuned to find out!

In this episode, we are joined by classical hematology experts, Madeleine Ochs, PharmD, BCOP and Justin Arnall, PharmD, BCOP, to teach us hemophilia 101!

In this T-Swift themed, episode, we discuss the history of hemophilia treatment (through the "eras") and how new agents may change the management of hemophilia patients.

In part two of this two-part episode, Bernie Marini and Anthony Perissinotti discuss the use of rituximab in acute lymphoblastic leukemia (ALL), based on the recent publication of the UKALL14 study (Marks, et al. Lancet Haematol, 2022): https://pubmed.ncbi.nlm.nih.gov/35358441/. We also discuss the previously published GRAALL study that evaluated rituximab in ALL (Maury, et al. NEJM, 2016, https://pubmed.ncbi.nlm.nih.gov/27626518/), and what we can conclude from the literature to date. The data surprises us, and makes us question our own practices!

In this episode, Anthony and Bernie chat with Chris Booth, MD, and Aaron "Papa Heme" Goodman, MD, to talk about the Common Sense Oncology movement!

Join the Common Sense Oncology movement at this link (it's free!): https://commonsenseoncology.org/

Lancet Oncol paper: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00319-4/fulltext

In this episode, Anthony and Bernie are joined by two special guests to discuss recent updates to the use of blinatumomab in both adult and pediatric acute lymphoblastic leukemia (ALL), including the results of the AALL1731 trial and the full publication of ECOG1910.

Julia Brown, PharmD, a Pediatric Hematology/Oncology Clinical Pharmacist and Lydia Benitez, an Adult Outpatient Leukemia Clinical Pharmacist bring their unique perspectives and expertise on the proper incorporation of blinatumomab into ALL care, as well as some of the major practical nuances that will be helpful to providers across the globe!

Finally, for all of the Oncology Pharmacists in the audience, don't forget to fill out the HOPA Practice Outcomes and Professional Benchmarking Committee Survey!