AML Round Table: What's Next if You Relapse?

This HealthTree Round Table for AML took place on September 17th, 2022.

Topic: Decision Making in AML: What's Next After Relapse?

Experts: Dr. Eunice Wang and Dr. Amanda Przespolewski from Roswell Park Cancer Center in Buffalo, NY, Dr. Lourdes Mendez from Yale Cancer Center and Dr. Jane Liesveld from Rochester University in Rochester, NY

DR. EUNICE WANG: MRD STATUS: HOW IT AFFECTS YOUR CHANCES OF RELAPSE

Important Notes from Dr. Wang's Presentation:

Acute Myeloid Leukemia (AML)
— Disease of older adults
— Biologically diverse
— Clinically aggressive

It is important to know your specific type of AML.

Pathway to a cure: Intensive chemotherapy

Diagnosis — [INDUCTION] — Complete response (CR) — [CONSOLIDATION] — CR— [MAINTENANCE/TRANSPLANT] — Cure

What is MRD? This means minimal residual disease. It is residual leukemia not detected by morphology (<5% blasts)

How is MRD detected?

1. Real-time PCR: Lower levels of disease are detectable by PCR. It takes longer, normal marrow expression.
2. Multiparameter flow cytometry: More immediately available.
3. Next generation sequencing: Multiple mutaitons can be analyzed in 1 single sample. Detects all mutations. Only used in clinical trials.

When should we test for MRD? Whenever you get a treatment change. 

Some insights regarding MRD:

• If you are MRD negative, your overall survival is much improved.
• Measurement of MRD has the potential to replace morphologic complete response as criteria of response to AML therapy
• Provides independent prognostic information: survival, relapse, outcomes
• Marker of resistance to therapy
• The goal is to better tailor therapy for curative intent.

Some Q&A with Dr Wang:

1. (14:42) When people look for a specialist, should they be looking for someone that does MRD testing?
2. (15:35) What medications are used during stem cell transplant to reduce MRD?
3. (16:42) If MRD testing starts to rise, at what level should practitioners start thinking that they may have a relapse?

DR. AMANDA PRZESPOLEWSKI - WHAT IF I RELAPSE AFTER TRANSPLANT?

Important Notes from Dr. Przespolewski's Presentation:

The amount of disease burden prior to transplant is measured by your MRD status.
MRD needs to be measured prior to and after bone marrow transplantation.
Being MRD positive is related to post-transplant relapse
There is a study going on for prevention of post-transplant relapse. The SORMAIN study is evaluating “sorafenib” which is a FLT3 inhibitor
Other options to prevent relapse currently being tested in clinical trials are:

• FLT3 inhibitor: CRENOLANIB
• IDH1 inhibitor: IVOSIDENIB
• BCL2 inhibitor: VENETOCLAX 
• AML vaccine and cellular therapy

Treatment of post-transplant relapse:

• Goals: quality of life and good psychosocial situation
• Take uncontrollable factors into account such as: age, comorbidities and performance status
• Clinical trials are very important: www.clinicaltrials.gov
• Donor lymphocyte infusion: with azacitidine therapy between each infusion. This is modestly effective with a 60% 2 year overall survival (in MRD positive patients post-transplant). 
• In patients who are not eligible for clinical trials: azacitidine + venetoclax post-transplant is a good combination of drugs. Overall response rates are 38%.
• Intensive or aggresive salvage chemotherapy are for very specific patients: very fit, >1 year post-transplant. Examples include CLAG + M (cladribine, cytarabine, G-CSF), FLAG + IDA (fludarabine, cytarabine and filgrastim), MEC (mitoxantrone, etoposide, cytarabine) 
• Second allogenic stem cell transplant: for very fit patients who are MRD negative, patients with availability of alternative donor, with no ongoing graft-versus-host disease

DR. JANE LIESVELD- CLINICAL TRIALS IN RELAPSED/REFRACTORY AML

Important Notes from Dr. Liesveld's Presentation:

There are approximately 258 studies listed for relapsed/refractory AML

Phases of clinical trials:

• PHASE 1: Is it safe?
• PHASE 2: Does it seem to work?
• PHASE 3: Does it work better than what is already out there?
• PHASE 4: After drug approval to learn more

 There are different kinds of trials:

•     Trials that involve treatment
•     Trials that don’t involve treatment
•     Studies just to observe patients

Is there something influencing the decision to participate?

Motivation is very personal and private
Benefits obtained from enrolling
Altruism — research is the BEST way to help science!
Vulnerability in elderly or frail patients, or patients with comorbidities

Some questions to ask yourself:

• How long will I be on trial?
• What is the goal of the trial?
• What are some side effects?
• Where will I have to go to participate?
• Are there any alternatives?
• Who is the sponsor and will this have any financial implications for me?

Barriers for patients:

• Testing and office visits are more often, this may be uncomfortable
• Concerns about safety
• Distance to facility can be too long for some patients
• Fear of being a “guinea pig”
• Fear about not receiving treatment; there is confusion about the term “placebo-controlled”

The likelihood a drug would pass all phases of clinical testing and get FDA approval was 7% for AML. Right now this number is a little bit higher.

COVID: There are no contraindications to COVID-19 vaccination while on trials

DR LOURDES MENDEZ - HOW TO MANAGE THE FEAR OF POTENTIAL RELAPSE

Important Notes from Dr. Mendez's Presentation:

The fear of recurrence or progression (FCR) is a common concern, and it can potentially affect quality of life. This interferes with medical care.

People who are especially vulnerable to FCR include:

• Young adults 
• Patients with pre-existing mental health conditions
• Patients with history of trauma

Wellness is key in this pathology, this is tied to interwoven elements of life. This is individual:

EMOTIONAL — INTELLECTUAL — PHYSICAL — SPIRITUAL

Matching care and FCR depends on its intensity:

MILD FCR: Self-help
MODERATE FCR: Peer support
SEVERE FCR: Pharmacotherapy and psychological counseling

Peer support includes:

• Online communities 
• Mentoring and coaching programs
• There are diverse links you can access provided by Dr. Mendez

One-on-one support: mentoring
*Imerman Angels is a cancer support community for this.

One-on-one support: Counseling

Psychological care is recommended — cognitive therapy and counseling are part of the treatment.

Therapy types:

• Cognitive behavioral therapy: challenging the validity of negative thoughts.
• Acceptance and commitment therapy: coping and processing negative thoughts, focusing on patient's values and life aims
• Metacognitive therapy: focus on controlling beliefs and responses that perpetuate emotional distress 

SUMMARY & GUIDING POINTS

1. Prioritize wellness
2. Communicate questions and concerns.
3. Reach out for professional support if required
4. Be kind to yourself and be positive!

Q&A SESSION

1.- (0:34) Are there any existing data or clinical trials for MRD regarding the RUNX1 mutation?
2.- (2:50) What are the four MRD testing options?
3.- (6:00) Does MRD show up before relapse, what about post-transplant? 
4.- (6:45) How often should you test MRD if you are in remission?
5.- (8:17) Do you have any tips for people undergoing clinical trials? How can you make that process a little bit easier?
6.- (10:00) Do you have any information on CAR-T cell therapy for AML?
7.- (11:30) If someone relapses after transplant, even with maintenance, with certain genetics, what is your advice?
8.- (14:12) What about the use of marijuana to deal with pain and anxiety?